Javtor/biomedical-topic-categorization-2022only-cased

Subphenotypes of acute kidney injury in adults. Acute kidney injury is a heterogeneous syndrome and as such is associated with multiple predisposing conditions and causes all of which affect outcomes. Such heterogeneity may conceal the potential benefit of therapies when generally applied to patients with acute kidney injury (AKI). The discovery of pathophysiology-based subphenotypes could be of benefit in allocating current and future therapies to specific groups.

0

1

0

1

0

Genetic association of toxin production in the dinoflagellate Alexandrium minutum . Dinoflagellates of the genus Alexandrium are responsible for harmful algal blooms and produce paralytic shellfish toxins (PSTs). Their very large and complex genomes make it challenging to identify the genes responsible for toxin synthesis. A family-based genomic association study was developed to determine the inheritance of toxin production in Alexandrium minutum and identify genomic regions linked to this production. We show that the ability to produce toxins is inheritable in a Mendelian way, while the heritability of the toxin profile is more complex. We developed the first dinoflagellate genetic linkage map. Using this map, several major results were obtained: 1. A genomic region related to the ability to produce toxins was identified. 2. This region does not contain any polymorphic sxt genes, known to be involved in toxin production in cyanobacteria. 3. The sxt genes, known to be present in a single cluster in cyanobacteria, are scattered on different linkage groups in A. minutum . 4. The expression of two sxt genes not assigned to any linkage group, sxtI and sxtG , may be regulated by the genomic region related to the ability to produce toxins. Our results provide new insights into the organization of toxicity-related genes in A. minutum , suggesting a dissociated genetic mechanism for the production of the different analogues and the ability to produce toxins. However, most of the newly identified genes remain unannotated. This study therefore proposes new candidate genes to be further explored to understand how dinoflagellates synthesize their toxins.

0

1

Mask-Wearing Perception of Preschool Children in Korea during the COVID-19 Pandemic: A Cross-Sectional Study. As the COVID-19 pandemic continues, wearing a mask has become a daily routine in Korea over the last two years. This study aims to investigate the mask-wearing perception of preschoolers (ages 4-6). The questionnaire comprised 17 yes-no closed-ended questions and two open-ended questions, and interviews of the children were conducted from January to February 2022, 15 months after mandatory mask wearing. Results showed that children were aware of the need to wear a mask to protect themselves and others from the coronavirus, and they perceived it as necessary and a good thing. Most children responded that they did not feel uncomfortable wearing a mask at preschool. This perception was thought to be influenced by the caregivers' perceptions of the mask in Korea. The way in which 4-5-year-olds perceived the mask differed from the way 6-year-olds did. Children aged between four and five seemed to perceive the mask as a physical self, while children aged six did not. As children who have experienced COVID-19 are growing up, attention is being focused on how the experience of wearing a mask affects their early childhood development.

0

1

0

1

0

Development and Verification of a Combined Diagnostic Model for Sarcopenia with Random Forest and Artificial Neural Network. Sarcopenia is a chronic disease characterized by an age-related decline in skeletal muscle mass and function, and diagnosis is challenging owing to the lack of a clear "gold standard" assessment method.

0

1

0

1

0

Tree nut-induced anaphylaxis in Canadian emergency departments: Rate, clinical characteristics, and management. Data are sparse regarding tree nut-induced anaphylaxis (TNA).

0

1

0

Bioactive characterization of ultrasonicated ginger (Zingiber officinale) and licorice (Glycyrrhiza Glabra) freeze dried extracts. Ginger (Zingiber officinale) and Licorice (Glycyrrhiza glabra L.) are one of the most popular spices having a wide range of bioactive compounds that have varied biological and pharmacological properties. The study was aimed to extract polyphenols from Himalayan medicinal herbs ginger and licorice in different solvents using ultra-sonication technique. The extraction efficiency (EE) was determined, and the extracts were characterized for physical properties (particle size, colour values), total phenolics, flavonoids, antioxidant properties, and structural and morphological features. Ultra-sonicated ginger in aqueous phase had the highest EE of polyphenols (15.27%) as compared to other solvents. Similar trend was observed in licorice with EE of 30.52 % in aqueous phase followed by ethanol: water (50: 50), and methanol: water (50:50) with 28.52% and 26.39%, respectively. The preliminary screening showed the presence of tannins, phenolics, flavonoids, saponins and carbohydrates, steroids and alkaloids in all the extracts. The phenolic and flavonoid content of dried ginger was found higher in ethanolic extracts compared to fresh ones as revealed by HPLC. Similarly, for licorice, the ethanolic fractions had the highest polyphenolic content. The representative samples of ginger (ethanol: water 75:25 and ethylacetate: water 75:25) and licorice (ethanol: water 70:30 and methanol: water 50:50) were studied for FESEM and particle size. The results showed the agglomerated extract micro-particles with a diameter of 0.5-10 µm and increased particle size (ginger: 547 and 766 nm), and (licorice: 450 and 566 nm). The findings could be beneficial for the advancement of ginger and licorice processing, for the comprehension of these herbs as a source of natural antioxidants in different food formulations.

0

1

0

Chest CT in the evaluation of child abuse - When is it useful? Indications for chest CT in evaluation of child abuse are unknown.

0

1

0

1

0

Cluster B personality disorders and its associated factors among psychiatric outpatients in Southwest Ethiopia: institutional-based cross-sectional study. Diagnosis of co-occurring personality disorders, particularly the most comorbid cluster B personality disorders in psychiatric patients is clinically important because of their association with the duration, recurrence, and outcome of the comorbid disorders. The study aimed to assess the prevalence of cluster B personality disorders and associated factors among psychiatric outpatients in Jimma Medical Center.

0

1

0

1

0

MRI-guided DBS of STN under general anesthesia for Parkinson's disease: results and microlesion effect analysis. The efficacy of the subthalamic nucleus (STN) stimulation for Parkinson's disease has been widely established. The microlesion effect (MLE) due to deep brain stimulation (DBS) electrode implantation has been reputed to be a good predictor for long-term efficacy of the procedure but its analysis in asleep implantation is still unclear. We thus analyzed MLE rate in our strategy of targeting the STN on MRI under general anesthesia and its correlation with our long-term results.

0

1

0

1

0

1

0

Fractal features of soil grain-size distribution in a typical Tamarix cones in the Taklimakan Desert, China. Tamarix cones play key roles in preventing sand erosion and maintaining regional ecosystem stability. This study aimed to explore the characteristics of soil grain size distribution (GSD) in Tamarix cones across the Taklimakan Desert, verify the relationships between soil grain composition and the fractal dimension, and analyze the relationships between soil GSD and environmental factors. Soils of the Tamarix cones from 0 to 500 cm soil depth were sampled every 20 cm at four sites (Qiemo, Qira, Aral, and Tazhong) along the periphery to the hinterland of the Taklimakan Desert. A total of 300 soil samples were collected to measure soil grain sizes and soil properties. Soil grain size composition was dominated by silt and very fine sand, and the fraction of fine particles decreased and that of the coarse particles increased with soil depth, except for at Tazhong. This suggested that suspension-size particles are the main component of the soil GSD and decrease with the increasing depth in the profiles at the Tamarix cones. The soils were poorly and moderately poorly sorted. Kurtosis generally showed a mesokurtic peak, and the GSD was negatively skewed towards the coarser particles. The fractal dimensions of GSD decreased in the following order Qiemo (2.30) > Qira (2.07) > Aral (1.99) > Tazhong (1.96) because of the increase of coarse particles. The fractal dimension had a strong positive correlation with the clay and silt fractions, and a strong negative correlation with the sand fraction, indicating that the fractal dimension can reflect the characteristics of the soil GSD. The strong relationships between the fractal dimensions and selected soil properties indicate that the fractal dimension can not only quantify changes in soil properties, but also reflect the degree of desertification and degradation in the desert region. Considering the strong wind activities and different deposition sources in the Taklimakan Desert, this study provides a deep insight into the soil formation processes of Tamarix cones within extreme arid desert ecosystems.

0

1

0

1

0

Development and validation of a blood-based genomic mutation signature to predict the clinical outcomes of atezolizumab therapy in NSCLC. We designed this study to develop a blood-based genomic mutation signature (bGMS) model for predicting the efficacy of atezolizumab therapy in non-small cell lung cancer (NSCLC) in a non-invasive manner.

0

1

0

Fabrication of Ce-doped DUT-52 as a sorbent for dispersive solid phase extraction of estrogens in human urine samples. A cerium (Ce)-doped metal-organic framework composite (Ce/DUT-52) was prepared by using a solvothermal method and was explored as a sorbent for dispersive solid phase extraction (DSPE) of three estrogens (α-estradiol, estrone, and hexestrol) in human urine samples. After doping with Ce(III), Ce/DUT-52 exhibited more attractive features involving a higher specific surface area (774.7 m 2 g -1 ) and zeta potential (31.4 mV), which made it an efficient adsorbent for the separation and enrichment of estrogens. The factors influencing DSPE efficiency such as the adsorbent amount, extraction time, pH, NaCl concentration, elution solvent and elution volume were investigated in detail. Under the evaluated conditions, Ce/DUT-52 showed good reusability ( n = 6, RSDs ≤ 4.8%). Notably, the cofunction of electrostatic interaction, hydrophobic interaction, hydrogen bonding and π-π interaction might play major roles between estrogens and Ce/DUT-52. Finally, coupled with high-performance liquid chromatography (HPLC), a fast and sensitive method was established, which provided low limits of detection (1.5-2.0 ng mL -1 ), wide linear ranges (3-500 ng mL -1 ) and satisfactory recoveries (79.8-96.1%). The results demonstrated that Ce/DUT-52 had excellent adsorption ability to the targets and the developed method provided an alternative strategy for the determination of trace estrogens or other compounds with similar chemical structures in urine samples.

0

1

0

1

0

1

0

Self-reported daytime napping, daytime sleepiness, and other sleep phenotypes in the development of cardiometabolic diseases: a Mendelian randomization study. Sleep disorders are associated with an increased risk of cardiometabolic diseases in observational studies, but the causality remains unclear. In this study, we leveraged two-sample Mendelian randomization (MR) analyses to assess the causal associations of self-reported daytime napping, daytime sleepiness, and other sleep phenotypes with cardiometabolic diseases including ischaemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and Type 2 diabetes mellitus (T2DM).

0

1

0

1

0

1

0

In vitro evaluation of zearalenone toxicity by comet assay. The aim of this study was to reveal the potentially genotoxic effect of zearalenone on bovine lymphocytes by comet assay in vitro. The bovine lymphocytes were exposed to various zearalenone concetrations (50; 10; 2; 0.4 and 0.08 ppm). The viability and DNA damage of lymphocytes was monitored after 2 h, 24 h, 48 h and 72 h. After 2 hours of zearalenone exposure, statistically significant DNA damage occurred at all tested concentrations of 0.08 ppm (12.2±1.25; p⟨0.05), 0.4 ppm (12.7±0.88; p⟨0.01), 2 ppm (12.0±0.51; p⟨0.01), 10 ppm (11.2±0.47; p⟨0.01) and at 50 ppm (14.2±0 61; p⟨0.001). Significantly greater DNA damage was also found after 24 h, 48 h and 72 h. The obtained results showed that zearalenone may induce DNA damage of the bovine lymphocytes.

0

1

0

1

0

Teaching Spanish using the pharmacists' patient care process. The Hispanic population of the United States now comprises the largest minority and is expected to increase. Student pharmacists must be prepared to care for this segment of the population. Efforts to learn medical Spanish will assist in these endeavors.

0

1

0

1

0

Mechanistic Origin of Favorable Substituent Effects in Excellent Cu Cyclam Based HNO Sensors. HNO has broad chemical and biomedical properties. Metal complexes and derivatives are widely used to make excellent HNO sensors. However, their favorable mechanistic origins are largely unknown. Cu cyclam is a useful platform to make excellent HNO sensors including imaging agents. A quantum chemical study of Cu cyclams with various substitutions was performed, which reproduced diverse experimental reactivities. Structural, electronic, and energetic profiles along reaction pathways show the importance of HNO binding and a proton-coupled electron transfer mechanism for HNO reaction. Results reveal that steric effect is primary and electronic factor is secondary (if the redox potential is sufficient), but their interwoven effects can lead to unexpected reactivity, which looks mysterious experimentally but can be explained computationally. This work suggests rational substituent design ideas and recommends a theoretical study of a new design to save time and cost due to its subtle effect.

0

1

0

1

0

Clinical relevance of amyloid in prostate samples: a report on 40 patients. To describe the clinical findings in patients with incidental prostatic amyloidosis.

0

1

0

1

0

Maternal cadmium exposure impairs placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling. Cadmium is a ubiquitous environmental pollutant, which can increase the risk of preeclampsia. This study was designed to determine the mechanism of cadmium exposure during pregnancy impaired placental angiogenesis that was associated with the occurrence of preeclampsia. The effects of cadmium exposure on placental thyroid hormone receptor signaling were explored. JEG3 cells were treated with CdCl 2 (20 μM) and the Dio2 inhibitor, IOP (100 μM). Cadmium levels in maternal blood and placentae were increased in preeclampsia group. Placental angiogenesis of preeclampsia was decreased with decreased expression of PLGF and VEGF and increased expression of sFlt1. Meanwhile, the expression and nuclear translocation of thyroid hormone receptor α were decreased in preeclampsia placenta, as well as the expression of Dio2, but not the expression and nuclear translocation of thyroid hormone receptor β. Furthermore, we found that cadmium exposure downregulated the expression of thyroid hormone receptor α and Dio2, but not the expression of thyroid hormone receptor β in JEG3 cells. Also, we found that cadmium exposure decreased the expression of PLGF and VEGF and increased the expression of sFlt1 in JEG3 cells. IOP pretreatment decreased the expression of PLGF and increased the expression of sFlt1. In conclusion, our results elucidated that cadmium exposure would impair placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling.

0

1

0

1

0

Research progress of microneedles in the treatment of melanoma. Melanoma is an aggressive malignancy deriving from melanocytes, which is characterized by high tendency of metastases and mortality rate. Current therapies for melanoma, like chemotherapy, immunotherapy and targeted therapy, have the problem of systemic exposure of drugs, which will lead to many side effects and premature degradation of drugs. The resulting low drug accumulation at the lesion limits the therapeutic effect on melanoma and makes the cure rate low. As an emerging drug delivery system, microneedles (MNs) can efficiently deliver drugs through the skin, increase the drug distribution in deeper tumor sites and minimize the leakage of therapeutic drugs into adjacent tissues, thus improving the therapeutic effect. In addition, compared with traditional drug delivery methods, MN-based drug delivery system has the advantages of simplicity, safety and little pain. So MNs can be developed for the treatment of melanoma, which can relieve the pain of patients and improve the survival rate. This review aims to introduce an update on the progress of MNs as an innovative strategy for melanoma, especially when MNs combining with different therapies against melanoma, such as chemotherapy, targeted therapy, immunotherapy, photothermal therapy (PTT), photodynamic therapy (PDT) and synergic therapy.

0

1

0

Antibiotic prescription practices amongst veterinarians in Nigeria. The high rate of antibiotic resistance constitutes a global threat to the continuous use of these drugs, because of increasing treatment failures. The aim of this study was to survey antibiotic prescription practices of veterinarians and the possible contribution to antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in Nigeria during the COVID era. This was a cross-sectional study that used a 33-question survey questionnaire administered to registered veterinarians in Nigeria. The study was both online survey and hard copy administered during the annual meeting of the veterinarians from July to October 2021. Descriptive statistics, bivariate analysis using Chi-square test were also done to analyze the results, while a two-tailed P-value of <0.05 at 95% confidence level was considered statistically significant. IBM SPSS Version 26 was used to analyze the data. A total of 172 respondents completed the online and hard copy questionnaire. Majority of the respondents engaged majorly in mixed veterinary practice (72.1%). A total of 53.5% were aware of the country's policy concerning antibiotic prescription, while majority (64.5%) do not do culture and sensitivity before antibiotic prescription. Majority (34.3%) felt that the risk of potential adverse drug reaction could affect their decision when choosing to prescribe an antibiotic to the owner. Majority (51.2%) felt that some antibiotics were over prescribed, while 26.7% opined that all antibiotics were appropriately prescribed. To improve antibiotic use and practice amongst veterinarians in Nigeria, dependence on laboratory services for antibiotic prescription, enforcement of national guidelines and monitoring of antibiotic prescription amongst the veterinarians is essential to curb over-prescription and strengthen antimicrobial stewardship.

0

1

0

1

0

1

0

Noncoding RNAs Emerging as Drugs or Drug Targets: Their Chemical Modification, Bio-Conjugation and Intracellular Regulation. With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed.

0

1

0

1

0

Novel 11β-substituted estradiol conjugates: Transition from ERα agonizts to effective PROTAC degraders. Endocrine therapy is widely used in clinic for breast cancer treatment, but long-term treatment inevitably causes drug resistance. Most of endocrine therapy-resistant breast cancers continue to depend on ERα signaling for growth and survival. In this regard, small molecule-induced ERα degradation, i.e. proteolysis targeting chimeras (PROTACs), represents an effective strategy to overcome endocrine resistance. Herein, we describe the design, synthesis, and biological evaluation of novel ERα-targeting PROTACs, wherein a E3 ligase ligand was attached to the 11β-position of estradiol via various linkers. Our efforts have identified a potent ERα PROTAC 15b that achieved excellent ERα degradation activity (DC50 = 67 nM) and induced comparable inhibition of cell growth to that of fulvestrant in MCF-7 cells. Besides, 15b displayed antagonistic effects in uterine cells and favorable physicochemical properties, making it as a good lead compound for further development as anti-breast agents.

0

1

0

1

0

TMT-based quantitative proteomic and physiological analyses on lotus plumule of artificially aged seed in long-living sacred lotus Nelumbo nucifera. Seed longevity is important for the maintenance of seed nutritional quality, vigor, and germination potential during storage. Sacred lotus is known as one of the longest living seeds in the world and their ability to maintain longevity has been widely investigated. In this study, a suitable controlled deterioration treatment (CDT) method was first established to evaluate the vigor loss of lotus plumule (LP), and then the Tandem Mass Tags (TMT)-based proteomic analysis was performed on LP from the CDT-treated seed to quantitatively and qualitatively analyze the protein profile dynamic. In total, 4002 proteins were successfully quantified, of them, 558 differently accumulated proteins (DAPs) were identified. Protein processing and RNA-related proteins were found more easily to be affected by CDT, which may directly result in seed vigor loss. Meanwhile, CDT resulted in remarkable up-regulation of numerous proteins related to antioxidation, photosynthesis, RNA and DNA stability, starch and sucrose mobilization, and cell membrane and wall stability, which potentially played key roles in maintaining the lotus seed vigor under CDT. Histological and physiological analyses were also performed to verify some proteome results. This study provided both fundamental data and new insights to further uncover the secret of lotus seed longevity. SIGNIFICANCE: Seed aging affects the seed quality and can result in direct economic losses. The exceptional longevity of sacred lotus seed has attracted extensive attention. In this study, an optimized CDT method was used to mimic the natural aging process of sacred lotus seed, and based on TMT-based quantitative proteomic analysis on the LP profile of CDT-treated seeds, a series of differentially accumulation of specific proteins (DEPs) were revealed related to CDT resistance. Correspondingly, the physiological state and histological structure of the LP along with the CDT were detected to verify the proteome data. This study provided comprehensive information for the molecular basis of lotus seed aging analysis and facilitate to screen seed longevity related proteins for other plant species.

0

1

0

Continuous clonidine infusion: an alternative for children on mechanical ventilation. This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the cumulative dose of other sedatives and the hemodynamic response.

0

1

0

1

0

1

0

The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function. Changing composition of the gut microbiome is an important component of the gut adaptation to various environments, which have been implicated in various metabolic diseases including obesity and type 2 diabetes, but the mechanisms by which the microbiota influence host physiology remain contentious. Here we find that both diets high in the fermentable fiber inulin and vertical sleeve gastrectomy increase intestinal expression and circulating levels of the anti-microbial peptide Reg3g. Moreover, a number of beneficial effects of these manipulations on gut function, energy balance, and glucose regulation are absent in Reg3g knockout mice. Peripheral administration of various preparations of Reg3g improves glucose tolerance, and this effect is dependent on the putative receptor Extl3 in the pancreas. These data suggest Reg3g acts both within the lumen and as a gut hormone to link the intestinal microbiome to various aspects of host physiology that may be leveraged for novel treatment strategies.

1

0

1

0

1

0

1

0

[Progress in research of population size estimation by network scale-up method]. Network scale-up method is an indirect population size estimation method based on social network theory. It is widely used in estimating the hidden population size because it does not need to contact the target population. In order to provide reference for the further application of this method, this paper summarizes the traditional network scale-up method, the progress of this method and its combination with new survey techniques.

0

1

0

The Construction and Analysis of a ceRNA Network Related to Salt-Sensitivity Hypertensives. Salt-sensitivity hypertensives (SSH) are an independent risk factor for cardiovascular disease. However, the mechanism of SSH is not clear. This study is aimed at constructing a competing endogenous RNA (ceRNA) network related to SSH.

0

1

0

1

0

1

0

Bottom-up design of hydrogels for programmable drug release. Hydrogels are a promising drug delivery system for biomedical applications due to their biocompatibility and similarity to native tissue. Programming the release rate from hydrogels is critical to ensure release of desired dosage over specified durations, particularly with the advent of more complicated medical regimens such as combinatorial drug therapy. While it is known how hydrogel structure affects release, the parameters that can be explicitly controlled to modulate release ab initio could be useful for hydrogel design. In this review, we first survey common physical models of hydrogel release. We then extensively go through the various input parameters that we can exercise direct control over, at the levels of synthesis, formulation, fabrication and environment. We also illustrate some examples where hydrogels can be programmed with the input parameters for temporally and spatially defined release. Finally, we discuss the exciting potential and challenges for programming release, and potential implications with the advent of machine learning.

0

1

0

1

0

Direct recovery of Zn from wasted alkaline batteries through selective anode's separation. In the present study, a leaner process for recovering zinc from spent alkaline batteries is studied at a laboratory scale. Such process is part of a diagram, under development, that aims at maximizing the value of all the battery components while reducing the costs of treatment and the environmental footprint involved in recycling this waste. It starts by a physical and selective pre-treatment stage that separates the anode from the remaining components followed by neutral leaching (three washing cycles at room temperature, S/L ratio of 1/5 (w/v), magnetic stirring for 15 min and settling during 45 min), acid leaching of the washed solid (4 mol/L of sulphuric acid, S/L ratio of 1/3 (w/v), 120 min at room temperature under magnetic stirring) and, finally, electrowinning of zinc from the pregnant leach solution (100 mA/cm 2 , 120 min under slow magnetic stirring). By leaching the anode alone, it is possible to obtain a solution rich in zinc (86 g/L), with very low concentration of other metals (<0.08 g/L). Such solution was adequate for zinc electrowinning, allowing an average recovery rate of 58%, without applying any purification stages, at the same time regenerating sulphuric acid for its recirculation. In conclusion, the results demonstrate that a more specific physical pre-treatment stage is highly desirable to recycle spent alkaline batteries in order to reduce the number of stages involved and the overall complexity, thus, reducing the costs involved and the potential environmental impacts, while maintaining high recovery rates of zinc.

0

1

0

1

0

The histone methyltransferase SETD2 negatively regulates cell size. Cell size varies between cell types but is tightly regulated by cell intrinsic and extrinsic mechanisms. Cell size control is important for cell function, and changes in cell size are frequently observed in cancer. Here, we uncover a role for SETD2 in regulating cell size. SETD2 is a lysine methyltransferase and a tumor suppressor protein involved in transcription, RNA processing and DNA repair. At the molecular level, SETD2 is best known for associating with RNA polymerase II through its Set2-Rbp1 interacting (SRI) domain and methylating histone H3 on lysine 36 (H3K36) during transcription. Using multiple independent perturbation strategies, we identify SETD2 as a negative regulator of global protein synthesis rates and cell size. We provide evidence that overexpression of the H3K36 demethylase KDM4A or the oncohistone H3.3K36M also increase cell size. In addition, ectopic overexpression of a decoy SRI domain increased cell size, suggesting that the relevant substrate is engaged by SETD2 via its SRI domain. These data add a central role of SETD2 in regulating cellular physiology and warrant further studies on separating the different functions of SETD2 in cancer development.

0

1

0

1

0

1

0

Role of salts and solvents on the defibrillation of food dye "sunset yellow" induced hen egg white lysozyme amyloid fibrils. Several food dyes are known to induce amyloid fibrillation when interacting with proteins. Here, we studied the role of sunset yellow (SY) in the amyloid fibrillation of hen egg white lysozyme (HEWL) and characterized the changes using spectroscopy techniques. Turbidity results showed that SY dye induces aggregation in HEWL in concentrations dependent manner. The aggregation induced by SY dye is kinetically very fast, no lag phase was detected, and the kinetics process follows an isodesmic kinetics pathway. The SY-dye induce aggregates have cross-β secondary structure confirmed by far-UV CD measurements. The effect of salts and solvents was also seen on SY-induced aggregates. Turbidity, far-UV CD, and kinetics results suggest that certain concentrations of NaCl and (NH 4 ) 2 SO 4 solubilize the SY-induce amyloid fibrils, but (NH 4 ) 2 SO 4 is more effective. Similarly, solvents are also solubilized the SY-induces HEWL amyloid fibrillation but the order of defibrillation is as follows: Isopropanol> ethanol > methanol which signified that isopropanol is more effective than other solvents. The salts and solvents data suggest that the electrostatic, as well as hydrophobic interaction, is responsible for SY-induced amyloid fibrillation. These conformational changes should be examined, more seriously for the purpose of food safety.

0

1

0

1

0

1

0

1

0

A Two-Workshop Collaborative, Integrated Scheduling Algorithm considering the Prescheduling of the Root-Subtree Processes. Aiming at the existing two-workshop integrated scheduling algorithm with the same equipment resources, a unified vertical or horizontal scheduling rule is used to sort all processes and ignore the vertical and horizontal characteristics of the associated process position in the process tree, which affects the scheduling results. A two-workshop collaborative, integrated scheduling algorithm considering the prescheduling of the Root-Subtree processes is proposed. The algorithm proposes a process conflict adjustment strategy for the horizontal equipment constraints. The same equipment Root-Subtree processes are sorted and loaded into the corresponding equipment queue through the vertical and horizontal prescheduling method in a single-workshop environment, and it combines with the schedulable process set to dequeue the first process of the queue. To enhance the flexibility of process scheduling, it proposes a process conflict adjustment strategy for the vertical process tree constraints in the two workshops to determine the processing workshop of the processes and the actual start time, which narrows the search comparison for schedulable processes. The example tests show that the algorithm not only excavates and utilizes the effectiveness of the vertical and horizontal characteristics of the process tree, but also considers the process migration time. Therefore, the effect is better and more practical.

0

1

0

1

0

1

0

Role of Autophagy in the Pathogenesis of Diabetes and Therapeutic Potential of Autophagy Modulators in the Treatment of Diabetes and Metabolic Syndrome. Autophagy is critically involved in the maintenance of intracellular nutrient homeostasis and organelle function. Dysregulated autophagy is likely to play a role in the development of metabolic disorders and diabetes because autophagy is critical in the rejuvenation of dysfunctional or stressed endoplasmic reticulum and mitochondria that play a crucial role in the development of diabetes. Indeed, systemic autophagy insufficiency led to the increased tissue lipid content, aggravated metabolic and finally more severe diabetes when metabolic stress was imposed, suggesting that autophagy insufficiency of dysfunction of lysosome, an effector organelle of autophagy, due to aging, genetic predisposition or environmental factors could be an underlying cause of diabetes. Conversely, autophagy enhancer could improve metabolic profile of obese mice by reducing tissue lipid content and ameliorating metabolic inflammation. Furthermore, clearance of human islet amyloid polypeptide (hIAPP) oligomer and amyloid that accumulate in pancreatic islets of > 90% of diabetes patients was also dependent on autophagy. Consistently, autophagy enhancer could improve glucose profile and β-cell function of transgenic mice expressing amyloidogenic hIAPP in pancreatic β-cells, which was accompanied by reduced accumulation of hIAPP oligomer or amyloid, ameliorated β-cell apoptosis and increased β-cell mass. These results suggest that autophagy enhancer could be a novel therapeutic modality against diabetes associated with lipid overload and human diabetes characterized by islet amyloid accumulation.

0

1

0

1

0

1

0

Utility of standard diffusion-weighted magnetic resonance imaging for the identification of ischemic optic neuropathy in giant cell arteritis. This study assessed diffusion abnormalities of the optic nerve (ON) in giant cell arteritis (GCA) patients with acute onset of visual impairment (VI) using diffusion-weighted magnetic resonance imaging (DWI). DWI scans of GCA patients with acute VI were evaluated in a case-control study. Two blinded neuroradiologists assessed randomized DWI scans of GCA and controls for ON restricted diffusion. Statistical quality criteria and inter-rater reliability (IRR) were calculated. DWI findings were compared to ophthalmological assessments. 35 GCA patients (76.2 ± 6.4 years; 37 scans) and 35 controls (75.7 ± 7.6 years; 38 scans) were included. ON restricted diffusion was detected in 81.1% (Reader 1) of GCA scans. Localization of ON restricted diffusion was at the optic nerve head in 80.6%, intraorbital in 11.1% and affecting both segments in 8.3%. DWI discerned affected from unaffected ON with a sensitivity, specificity, positive and negative predictive value of 87%/99%/96%/96%. IRR for ON restricted diffusion was κ inter = 0.72 (95% CI 0.59-0.86). DWI findings challenged ophthalmologic diagnoses in 4 cases (11.4%). DWI visualizes anterior and posterior ON ischemia in GCA patients with high sensitivity and specificity, as well as substantial IRR. DWI may complement the ophthalmological assessment in patients with acute VI.

0

1

0

[Family form of nephrogenic X-linked diabetes indiabetes]. There is a global trend towards an increase in the prevalence of diabetes insipidus. Symptoms of nephrogenic diabetes insipidus with X-linked inheritance appear in men, in women with heterozygous mutations, are characterized by an isolated symptom complex of polyuria, polydipsia, hypostenuria. In children, more often than in adults, with fluid restriction, a clinic of water-deficient dehydration develops with hypernatremia, hyperthermia, and plasma hyperosmolality. This manuscript presents a case of Nephrogenic diabetes insipidus, X-linked familial form in male patients.At the same time, in the family along the female line, the mother and grandmother also had an increased need for water, the use of minirin was ineffective. In the older brother and younger brother, clinical manifestations of diabetes insipidus in the form of severe thirst and polyuria were noted from infancy, after the examination, the diagnosis was made - diabetes insipidus and desmopressin was prescribed.Due to the lack of effect from the use of desmopressin, the analysis of exons and adjacent sections of the introns of the AQP2 and AVPR2 genes was carried out by PCR and subsequent direct sequencing. No mutations were found in the AQP2 gene. The hemizygous substitution S315I was found in the AVPR2 gene. The familial form X was confirmed - linked nephrogenic diabetes insipidus. A hypothiazide was recommended, against the background of constant intake of which only a slight positive trend is observed.

0

1

0

Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England. The SARS-CoV-2 Omicron subvariant, BA.2, may be less severe than previous variants; however, confounding factors make interpreting the intrinsic severity challenging.

0

1

0

1

0

1

0

Clinical Features and Treatment of Intra-Tendinous Suture Reaction Following Achilles Tendon Repair Using Nonabsorbable Suture Material: A Retrospective Case Series Study. We aimed to investigate the clinical manifestations, radiological findings, and therapeutic outcome of treatment for patients with surgically confirmed foreign body reaction following an Achilles tendon repair using non-absorbable suture material. Eight consecutive patients who were confirmed as having an intra-tendinous suture foreign body reaction in the histopathological report were enrolled in this study. Medical records of all patients in terms of clinical and radiological features were retrieved. Also, the outcome of treatment was evaluated at a follow-up of at least 12 months. All the patients complained of pain and a palpable mass around a previous surgical site at mean 25.1 months (range, 4-72 months) after the initial surgery. Magnetic resonance imaging (MRI) or ultrasound were used to detect the lesion. All the patients underwent surgical excision of foreign body reaction tissue and primary repair using absorbable suture material. After the treatment, the wounds were healed completely in all, and the average FAOS (foot and ankle outcome score) was 91.32 at mean follow-up for 22.4 months. In conclusion, intra-tendinous suture reaction is a rare complication following an Achilles tendon repair using nonabsorbable suture material, but it can be treated adequately with only surgical excision of foreign body reaction tissue and primary repair using absorbable suture material.

0

1

0

Cervical Joint Position Sense in Individuals With Type 2 Diabetes and Its Correlations With Glycated Hemoglobin Levels: A Cross-Sectional Study. This study aimed to compare cervical joint position sense (JPS) between individuals with type 2 diabetes (T2D) and healthy individuals and to assess the correlation between glycated hemoglobin (HbA1c) values and cervical JPS in individuals with T2D.

0

1

0

1

0

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021. The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years † with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

0

1

0

1

0

1

0

Internet-based imagery rescripting intervention for adult survivors of institutional childhood abuse in the former German Democratic Republic - a pilot study. Background: From 1949 to 1990, about 500,000 children and adolescents in the former German Democratic Republic (GDR) were placed in institutional care. Many of these individuals experienced physical and sexual abuse as well as general maltreatment. While this population group is in great need of psychosocial support, few low-threshold interventions aimed at the needs of adult survivors of institutional childhood abuse exist. Objective: This pilot study examines the efficacy of an internet-based imagery rescripting intervention in reducing psychopathological symptoms, within a population of survivors of institutional abuse from state childcare institutions, in the former GDR. Additionally, a case study is presented, depicting the treatment of a woman suffering from PTSD after having been institutionalised in the former GDR. Method: Participants received 10 internet-based writing assignments, based on the principles of imagery rescripting, specifically tailored to the needs of survivors of institutional childhood abuse in the GDR. The participants received personalised feedback on their assignments. Symptoms of posttraumatic stress disorder (PTSD), complex posttraumatic stress disorder (CPTSD), depression, and anxiety were assessed at pre- and post-treatment. Results: A total of 15 participants completed the intervention (mean age 56.2 years; 66.7% female). Paired t-tests showed a significant reduction of PTSD, CPTSD, depression, and anxiety symptoms. Large effect sizes were found for PTSD (d = 1.26), CPTSD (d = .97), depression (d = 1.08) and anxiety (d = 1.20). Conclusion: The results of this pilot study provide preliminary evidence for the efficacy and feasibility of the intervention in treating psychopathological symptoms in survivors of institutional abuse in the GDR. The case study additionally demonstrates the applicability of the intervention. A randomised controlled trial should be applied to further evaluate the intervention and its effects. Trial registration: German Clinical Trials Register identifier: DRKS00020266..

0

1

0

1

0

The Role of Blood-Brain Barrier Dysfunction in Mild Cognitive Impairment: a Scientometric and Visualization Analysis from 2000 to 2021. Mild cognitive impairment (MCI) is a pathological stage between normal cognitive aging and dementia. The blood-brain barrier (BBB) breakdown is emerging as an early biomarker of MCI. This study aimed to visually analyze the literatures related to MCI caused by BBB dysfunction in recent 20 years, systematically identify collaboration networks, track research trends, highlight current hot spots, and predict future frontiers in this field. The related literatures published from 2000 to 2021 were obtained from the Web of Science with the search term "mild cognitive impairment and (blood-brain barrier or neurovascular unit or neurovascular coupling)". VOSviewer software was used to present knowledge map, CiteSpace software was used to extract literature information and make tables, including the top most influential countries, authors, institutions, periodicals, keywords, and references. A total of 333 literatures were used for visual analysis. After 2013, the literatures in the field of BBB dysfunction-induced MCI showed an increased trend in terms of year of publication and quantity of material, with more than 40 publications published each year. USA, England, China, and Sweden cooperated closely. In terms of institutions, Harvard Med Sch ranked first in the number of papers published, followed by Mstricht Univ and Univ Washington. In terms of journals, three of the top five co-cited journals belonged to USA, the other two journals were Neurobiol Aging and J Alzheimers DIS, which were from England and Netherlands respectively. A total of 1752 authors were identified, with Abhay P Sagare the most published and Zlokovic BV the most cited. Keyword emergence detection analysis showed that inflammation, oxidative stress, and memory were new research hot spot in this field. Overall, the research on BBB dysfunction-induced MCI is booming. In the future, cooperation and communication between different countries and institutions should be strengthened.

0

1

0

1

0

Epigenetic modifications in metabolic memory: What are the memories, and can we erase them? Inherent and acquired abnormalities in gene regulation due to the influence of genetics and epigenetics (traits related to environment rather than genetic factors) underlie many diseases including diabetes. Diabetes could lead to multiple complications including retinopathy, nephropathy, and cardiovascular disease that greatly increase morbidity and mortality. Epigenetic changes have also been linked to diabetes-related complications. Genes associated with many pathophysiological features of these vascular complications (e.g., inflammation, fibrosis, and oxidative stress) can be regulated by epigenetic mechanisms involving histone posttranslational modifications, DNA methylation, changes in chromatin structure/remodeling, and noncoding RNAs. Intriguingly, these epigenetic changes triggered during early periods of hyperglycemic exposure and uncontrolled diabetes are not immediately corrected even after restoration of normoglycemia and metabolic balance. This latency in effect across time and conditions is associated with persistent development of complications in diabetes with prior history of poor glycemic control, termed as metabolic memory or legacy effect. Epigenetic modifications are generally reversible and provide a window of therapeutic opportunity to ameliorate cellular dysfunction and mitigate or "erase" metabolic memory. Notably, trained immunity and related epigenetic changes transmitted from hematopoietic stem cells to innate immune cells have also been implicated in metabolic memory. Hence, identification of epigenetic variations at candidate genes, or epigenetic signatures genome-wide by epigenome-wide association studies can aid in prompt diagnosis to prevent progression of complications and identification of much-needed new therapeutic targets. Herein, we provide a review of epigenetics and epigenomics in metabolic memory of diabetic complications covering the current basic research, clinical data, and translational implications.

0

1

0

Supporting students with sex chromosome aneuploidies in educational settings: Results of a nationwide survey. Children with sex chromosome aneuploidies (SCAs) are at an increased risk for neurocognitive and behavioral disorders that may interfere with academic success, including early developmental delays, learning disabilities, executive function problems, and social communication deficits. The present national survey aimed to update and extend our understanding of school supports and educational outcomes for students with these increasingly common genetic diagnoses. Parents of children with a diagnosed SCA, birth to 21 years, living in the United States (N = 248), responded to an electronic survey with questions focused on school support plans, academic accommodations, educational therapies, school completion, and perceptions of educator awareness of SCAs. Results revealed high rates of delayed kindergarten, grade retention in primary years, and educational support plans (IEPs = 71%; Section 504 Plans = 26%). A majority (73%) of respondents with children over age 18 years (N = 41) reported their children successfully completed high school, and nearly half (46%) pursued post-secondary education opportunities. Many parents reported their children's educators had little to no knowledge of SCA conditions, justifying a need to train teachers and policy makers in the unique educational needs of children and adolescents with SCAs. School psychologists should be aware of the frequent need for accommodations and individualized support plans in this population so they can support children and families by advocating for early and comprehensive evaluations and intervention plans.

0

1

0

1

0

1

0

Menaquinone-7 ameliorates cerebrovascular calcification-associated memory decline in aged mice. Menaquinone (MK)-7 is a vitamin K2 analog that functions as a cofactor of γ-glutamyl carboxylase involved in the activation of vitamin K (VK)-dependent proteins. The present study aimed to evaluate the effect of MK-7 on memory and cognitive function in aged C57BL/6 mice. Eighteen-month-old mice were raised for a further 4 months, fed on a standard or calcium-rich diet (3 % [w/w]), and were orally given MK-7 (40 and 400 μg/day/mouse) five times per week during the same period. The Morris water maze (MWM) test was performed at 19 and 22 months. The aged mice showed noticeable memory declines in the MWM test at all time points compared with 6-week-old mice, and this memory loss was significantly restored by the daily administration of high-dose MK-7 for 4 months. MK-7 administration also improved micro-computed tomography-based cerebrovascular calcification and aging-associated declines in growth arrest-specific 6, total and carboxylated matrix Gla proteins, and ganglioside levels in the brain of aged mice. It serologically reduced phosphorous levels in the blood, but not the urea, cholesterol, and calcium. Taken together, the long-term administration of MK-7 significantly improved age-related memory and cognitive impairments, possibly through inhibition of cerebrovascular calcification in aged mice, indicating that it can be used to develop new drugs for improving memory and cognitive function in older adults.

0

1

0

1

0

1

0

1

0

Spermidine Crosslinked Gellan Gum-Based "Hydrogel Nanofibers" as Potential Tool for the Treatment of Nervous Tissue Injuries: A Formulation Study. Aim of the work was to develop a potential neural scaffold, endowed with neuroprotective and neuroregenerative potential, to be applied at the site of nervous tissue injuries: nanofibers, consisting of gellan gum (GG), spermidine (SP) and gelatin (GL), were prepared via electrospinning. SP was selected for its neuroprotective activity and cationic nature that makes it an ideal GG cross-linking agent. GL was added to improve the scaffold bioactivity.

0

1

0

1

0

The impact of daylight on suicide rates. Since Durkheim and Morselli found a spring peak in suicides in the late 19th century, researchers have presented possible explanations, including daylight variation, for this seasonal pattern. Our identification strategy exploits the idiosyncratic variation in daylight within Norwegian regions, arising from the country's substantial latitudinal range. We use full population data for a period of 45 years in a pre-registered research design. We find a small and non-significant relationship: One extra hour of daylight increases the suicide rate by merely 0.75 % (95 % CI: -0.4 % to 1.9 %).

0

1

0

The perceptions of dental hygiene students about an asynchronous oral biology course. Medical and dental schools have long-established pedagogical approaches to teacher-centred face-to-face learning. The 3-year baccalaureate dental hygiene (DH) program at the University of Alberta, which enrolls 42 students of diverse ages and experiences each year, is no exception. Oral Biology II (OBIOL 302) is an intermediate-level course in the DH program; it was moved to an asynchronous online format to manage the disruptions of the COVID-19 pandemic. This mixed-method study explores the factors affecting the dental hygiene student experience in this online, asynchronous learning environment.

0

1

0

1

0

1

0

Live birth after transfer of a single euploid vitrified-warmed blastocyst according to standard timing vs. timing as recommended by endometrial receptivity analysis. To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of unsuccessful frozen embryo transfers (FETs).

0

1

0

1

0

Current best estimates of beam quality correction factors for reference dosimetry of clinical proton beams. Objective . To review the currently available data on beam quality correction factors,kQ,for ionization chambers in clinical proton beams and derive their current best estimates for the updated recommendations of the IAEA TRS-398 Code of Practice. Approach . The reviewed data come from 20 publications from whichkQvalues can be derived either directly from calorimeter measurements, indirectly from comparison with other chambers or from Monte Carlo calculated overall chamber factors,fQ.For cylindrical ionization chambers, a distinction is made between data obtained in the centre of a spread-out Bragg peak and those obtained in the plateau region of single-energy fields. For the latter, the effect of depth dose gradients has to be considered. To this end an empirical model for previously published displacement correction factors for single-layer scanned beams was established, while for unmodulated scattered beams experimental data were used. From all the data, chamber factors,fQ,and chamber perturbation correction factors,pQ,were then derived and analysed. Main results . The analysis showed that except for the beam quality dependence of the water-to-air mass stopping power ratio and, for cylindrical ionization chambers in unmodulated beams, of the displacement correction factor, there is no remaining beam quality dependence of the chamber perturbation correction factorspQ.Based on this approach, average values of the beam quality independent part of the perturbation factors were derived to calculatekQvalues consistent with the data in the literature. Significance . The resulting data from this analysis are current best estimates ofkQvalues for modulated scattered beams and single-layer scanned beams used in proton therapy. Based on this, a single set of harmonized values is derived to be recommended in the update of IAEA TRS-398.

0

1

0

1

0

1

0

First-ever Clinical Experience With Magnetic Resonance-based Lattice Radiotherapy for Treating Bulky Gynecological Tumors. Bulky gynecological tumors are a rare entity of large primary tumors, for which only a limited range of therapeutic options is available. Among these, when surgical approach is deemed unsuitable based on comorbidities and/or technical feasibility, radiotherapy is administered at low doses with palliative intent only. Aggressive treatment of such large primary tumors might significantly prolong patient survival and improve their quality of life by effectively delaying tumor progression to extra-pelvic sites. Lattice radiotherapy is a type of Spatially Fractionated Radiation Therapy, specifically devoted to treat and debulk large tumor masses, which are not candidates for normofractionated homogeneous high-dose radiotherapy schedules due to potential harmful dose-volume effects. The aim of this case study was to report on the feasibility of a Magnetic Resonance Imaging-based Lattice approach.

0

1

0

1

0

Iodine-Promoted Oxidative Cyclization of Methyl Azaarenes and α-Amino Ketones for One-Pot Synthesis of 2-Azaaryl-5-aryl Oxazoles. A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.

0

1

0

1

0

1

0

1

0

Synthesis of nuevamine and a cyano-chilenine analog via divergent C(sp 3 )-H bond functionalization of isoindolinone derivatives. Divergent C(sp 3 )-H bond functionalizations of isoindolinone derivatives were developed to synthesize nuevamine, a cyano-chilenine derivative, and two related analogs. A copper-catalyzed C-H cross-dehydrogenative coupling ( via cation formation) allowed the formation of a new C-C bond leading to the direct assembly of the isoindolo[1,2- a ]isoquinolinone tetracyclic system of the nuevamine. The syntheses of the cyano-chilenine derivatives were carried out by installing two nitrile groups under basic conditions ( via anion formation). Then, the isoindolobenzazepinic system of the chilenine skeleton was constructed by a Houben-Hoesch cyclization process. The present methodology has the advantage of not requiring the use of pre-functionalized substrates.

0

1

0

1

0

1

0

1

0

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development. Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1 Tg ) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1 Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

0

1

0

1

0

1

0

1

0

1

0

Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to host HLA-C genotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay between KIR/HLA immunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specific KIR/HLA-C combinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1 + individuals. Compared to 60 HIV-1 - controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C + and KIR3DL2 + NK cell sub-populations from HIV-1 + individuals was enlarged compared to HIV-1 - controls. Stratification along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1 + NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.

0

1

0

1

0

Management Strategy of Alzheimer's Patients under the Medical-Care Integration Model Based on Big Data Evaluation. In the context of the era of big data, the management of Alzheimer's patients has aroused widespread concern in the society. What should the elderly and people with dementia do and how the society should accommodate these special groups have aroused heated discussions in the society. The goal of the medical-nursing integration model is to realize the integrated model of medical care-nursing-rehabilitation-old care, and to better satisfy the needs by providing medical services, rehabilitation care, and health management. The medical needs of the elderly can help the elderly maintain a healthy state; the elderly care needs can be better met through elderly care services, and the burden on families and society can be reduced. With the advancement of the medical-care integration model, new solutions have been provided for the management of senile dementia patients. Therefore, under the medical-care integration model, this paper managed Alzheimer's patients based on the big data algorithm based on association rules and compared it with the management of Alzheimer's patients under the traditional model, and drew the following conclusions: compared with the management satisfaction of Alzheimer's patients under the traditional model, family members and patients' total satisfaction with nursing management under the medical-care integration model was greatly improved; compared with the management of Alzheimer's patients under the traditional model, the incidence of adverse events in the management of Alzheimer's patients under the medical-care integration model was greatly reduced, which was reduced to 17.6%; under the medical-care integration model, the anxiety and depression scores of the elderly patients with dementia decreased rapidly; under the medical-care integration model, the living ability of senile dementia patients has been greatly improved; the use of the medical-care integration model to manage senile dementia patients has greatly improved the sleep quality, mental quality, and quality of life of senile dementia patients.

0

1

0

Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update. Ocular drug delivery is one of the most challenging endeavors among the various available drug delivery systems. Despite having suitable drugs for the treatment of ophthalmic disease, we have not yet succeeded in achieving a proper drug delivery approach with the least adverse effects. Nanotechnology offers great opportunities to overwhelm the restrictions of common ocular delivery systems, including low therapeutic effects and adverse effects because of invasive surgery or systemic exposure. The present review is dedicated to highlighting and updating the recent achievements of nano-based technologies for ocular disease diagnosis and treatment. While further effort remains, the progress illustrated here might pave the way to new and very useful ocular nanomedicines.

0

1

0

1

0

Science communication activities at research institutes in Brazil: Recent expansion on the way to professionalization. This study was designed to analyze the science communication activities geared towards the general public undertaken at Brazilian research institutes. We identified how often such activities are carried out and what human and financial resources are available for them. The results suggest that between the years 2013 and 2017 there was an increase in science communication by research institutes responsible for a wide range of activities. To communicate with the public, the 169 institutes studied tend to use traditional communication channels more than social media. However, most of them did not have designated communication teams, drawing on specialized personnel from their host institution. Although they do engage in intensive communication activities, Brazilian research institutes still lack more a structured approach to science communication.

0

1

0

1

0

1

0

1

0

1

0

Single-Photon Emission Computed Tomographic Reverse Lymphatic Mapping for Groin Vascularized Lymph Node Transplant Planning. Superficial inguinal (groin) vascularized lymph node transplantation is the most common option for the treatment of lymphedema, particularly in combination with free abdominal flap breast reconstruction. This study examines the utility of single-photon emission computed tomographic (SPECT/CT) lymphoscintigraphy for lower extremity reverse lymphatic mapping in presurgical planning for groin vascularized lymph node transplantation and appraises the physiologic lymphatic drainage to the superficial inguinal lymph nodes.

0

1

0

1

0

The Effects of Appearance-Based Comments and Non-Appearance-Based Evaluations on Body Dissatisfaction and Disordered Eating Urges: An Ecological Momentary Assessment Study. The current study used ecological momentary assessment (EMA) to investigate whether appearance-based comments, social and performance-based evaluations affected levels of body dissatisfaction (BD) and urges to engage in disordered eating behaviors (DE) throughout daily life. A total of 620 participants completed a baseline questionnaire assessing sociodemographic variables. Participants then downloaded a mobile app which alerted them to complete short surveys assessing their levels of BD, DE urges, and experiences of receiving comments and evaluations six times per day for 7 days. Negative appearance-based comments predicted greater levels of state BD, while positive appearance comments predicted lower levels of state BD. Negative social and performance-based evaluations predicted an increase in state BD, while positive evaluations predicted a decrease in this outcome variable. No significant predictor was found for the DE urge outcomes. The present findings suggest that receiving negative and positive feedback in various domains of one's life may predict opposite outcomes for body image. However, these effects do not necessarily associate with urges to engage in DE in a nonclinical population.

0

1

0

1

0

[Geriatric syndromes and polypharmacy: to prescribe or to proscribe that is the question]. How to apply treatment recommendations from various knowledgeable specialist societies concerning the very complex patient? Within a population weakened by the cumulative effect of comorbidities, loss of autonomy aggravated by geriatric syndromes and biological changes linked to aging which interact with the pharmacokinetics and pharmacodynamics of drugs, there is fertile soil for the advent of adverse conditions linked to simultaneously prescribing multiple treatments. Our aim is to analyze various clinical reasoning tools permitting an appropriate drug prescription while considering the state of health, life expectancy and time to benefit with the aim of reducing iatrogenesis.

0

1

0

1

0

1

0

Dental Anomalies as Identification Strategies for Unknown Human Remains: Literature Review and Applications. The unique hard and resilient nature of human teeth makes them useful for various forensic odontological examinations. Structural alterations, cultural modifications, pathological variations, and restorative material make them excellent forensic indicators about biological identity of the unknown deceased or living individuals. Variations in the anatomical details of teeth may be imprinted by defective dental development, traumatic damages, pathologies, and nonmasticatory or weaponry use of teeth during an individual's lifetime. Such imprints can be used for comparisons and identification in forensic anthropology. Deliberate dental alterations/modifications and mutilations practiced due to cultural or esthetic purposes have been reported from some contemporary human population groups as well as from some ancient documented skeletal collections. Willful dental modifications have been most commonly done by filling, drilling, grooving, grinding, staining, and chipping. These dental features may be useful only for differentiation of varied anthropological populations, but their forensic utility cannot be ignored, particularly when antemortem dental records are available for comparisons. Various dental developmental anomalies and defects, restorations, pathological signatures, and occupational markers definitely corroborate other methods of forensic identifications, but cannot be used as sole criteria for individualization of unknown human remains retrieved in medicolegal scenarios. This review article attempts to glean information about various characteristic features of teeth and their forensic significance to aid identification of unknown human dental remains found in forensic contexts; its concluding emphasis focuses on the role of such dental individualities in identification strategies for human remains excavated from an abandoned ancient well situated underneath a religious structure at Ajnala (Amritsar), India. The unique dental features, extrinsic staining of anterior teeth, low frequency of dental pathologies, and notched incisors of those excavated remains were suggestive of them belonging to slain sepoy from an historic military regiment.

0

1

0

1

0

Decolorization and control of bromate formation in membrane ozonation of humic-rich groundwater. Membrane ozonation of bromide-containing, high-color natural organic matter (NOM) containing groundwater was performed using single-tube polydimethylsiloxane (PDMS) and multi-tube polytetrafluoroethylene (PTFE) membrane contactors, and compared to batch ozonation. For membrane ozonation, dissolved ozone concentration, water color (VIS 436 ), ultraviolet light absorption (UV 254 ) and bromate formation were correlated with ozone dose, ozone gas concentration, hydraulic retention time and Hatta number (Ha). NOM color removal of up to 45 % for the single-tube contactor and 17 % for the multi-tube contactor were achieved while containing bromate formation below 10 µg L -1 . Higher color removal using higher ozone doses was associated with high bromate formation i.e. >>10 µg L -1 . In membrane ozonation, low ozone gas concentrations, long hydraulic retention times and high Ha resulted in low dissolved ozone concentrations due to quenching of ozone by NOM. At specific ozone doses of < 0.5 mg O 3 /mg DOC and Ha > 1, single-tube ozonation resulted in comparable results to batch ozonation while bromate formation was higher in the single-tube contactor at specific ozone doses > 0.5 mg O 3 /mg DOC and Ha < 1. At comparable ozone doses and Ha, bromate formation in the multi-tube contactor was always higher compared to single-tube and batch ozonation. This could be associated with the uneven ozone distribution within the multi-tube contactor. Results show that ozone dose is the major driver for selectivity between bromate formation and NOM color removal in both membrane and batch ozonation. Bromate formation in membrane ozonation may be controlled by adjusting gas concentration, Ha and hydraulic retention time. Membrane module design and process parameters of membrane ozonation reactors significantly affect treatment performance and should be optimized for selective target compound removal over by-product formation.

0

1

0

1

0

1

0

1

0

1

0

1

0

Early and late predictors of postoperative neurocognitive dysfunction in cardiac surgery. Postoperative cognitive dysfunction (POCD) is a multifactorial image characterized by insufficiency in features such as the ability to perform tasks requiring high brain functions. Cognitive dysfunction such as memory loss and decreased concentration, confusion, and delirium are common conditions in some patients in the early period after major surgical interventions such as cardiac surgery. POCD causes delays in postoperative recovery, long return-to-work times, and decreased quality of life. This study aims to demonstrate POCD in early and late stages in patients undergoing cardiac surgery through the Montreal Cognitive Assessment (MoCA) and the Mini Mental Test (MMT). In addition, we aim to determine predictive factors with these neurocognitive tests.

0

1

0

1

0

Low-Dose Occupational Exposure to Nickel and Thyroid Hormones. The aim of this study was to evaluate the effects of a low-dose exposure to nickel, as it is present in urban air, on thyroid hormones and on thyrotropin in outdoor workers exposed to urban pollutants.

0

1

0

1

0

1

0

1

0

1

0

The preventive effect of internet-based cognitive behavioral therapy for prevention of depression during pregnancy and in the postpartum period (iPDP): a large scale randomized controlled trial. Prevention of perinatal depression beginning from the antenatal period is essential. Therefore, this study aimed to investigate the effectiveness of recently developed internet-delivered cognitive behavioral therapy (iCBT) for preventing the onset of a major depressive episode (MDE) in the third trimester and at 3 months postpartum.

0

1

0

1

0

[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis]. Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P =0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P =0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P <0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P =0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P <0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P =0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P =0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P =0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

0

1

0

[Pay close attention to the current characteristics and development trend of severe acute hepatitis with unknown etiology in children worldwide]. In the past, acute hepatitis of unknown etiology in children was sporadic. However, during the last three weeks, there has been a trend of short-term outbreak around the world. As of May 3, 2022, at least 228 cases had been reported in about 20 countries and regions. The main clinical manifestations of the children included abdominal pain, diarrhea, vomiting, jaundice, and hepatomegaly. The liver functions including alanine aminotransferase and total bilirubin increased sharply. About 8.8% of the children needed liver transplantation. The etiology is not clear, but adenovirus type 41 is currently considered to be the most likely cause. Clinicians should keep alert to acute hepatitis of unknown etiology in children, strengthen epidemic surveillance, clinical treatment, and carry out necessary health education.

0

1

0

Magnetic Resonance Imaging of Acute Abdominal Pain in the Pregnant Patient. Evaluation of a pregnant patient presenting with acute abdominal pain can be challenging to accurately diagnose for a variety of reasons, and particularly late in pregnancy. Noncontrast MR remains a safe and accurate diagnostic imaging modality for the pregnant patient presenting with acute abdominal pain, following often an initially inconclusive ultrasound examination, and can be used in most settings to avoid the ionizing radiation exposure of a computed tomography scan. Pathologic processes discussed in this article include some of the more common gastrointestinal, hepatobiliary, genitourinary, and gynecologic causes of abdominal pain occurring in pregnancy, as well as traumatic injuries.

0

1

0

1

0

The Intake of Ultra-Processed Foods and Prevalence of Chronic Kidney Disease: The Health Examinees Study. Emerging evidence links several health outcomes to the consumption of ultra-processed food (UPF), but few studies have investigated the association between UPF intake and kidney function. This cross-sectional study investigated the prevalence of chronic kidney disease (CKD) in relation to UPF intake in Korea. Data were obtained from the 2004-2013 Health Examinees (HEXA) study. The intake of UPF was assessed using a 106-item food frequency questionnaire and evaluated using the NOVA classification. The prevalence of CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/m 2 . Poisson regression models were used to compute the prevalence ratios (PR) of CKD according to quartiles of the proportion of UPF intake (% food weight). A total of 134,544 (66.4% women) with a mean age of 52.0 years and an eGFR of 92.7 mL/min/m 2 were analysed. The median proportion of UPF in the diet was 5.6%. After adjusting for potential confounders, the highest quartile of UPF intake was associated with the highest prevalence of CKD (PR 1.16, 95% CI 1.07-1.25), and every IQR (6.6%) increase in the proportion of UPF in the diet was associated with a 6% higher prevalence of CKD (PR 1.06, 95% CI 1.03-1.09). Furthermore, the highest consumption of UPF was inversely associated with eGFR (Q4 vs. Q1: β -1.07, 95% CI -1.35, -0.79; per IQR increment: (β -0.45, 95% CI -0.58, -0.32). The intake of UPF was associated with a high prevalence of CKD and a reduced eGFR. Longitudinal studies in the Korean population are needed to corroborate existing findings in other populations.

0

1

0

1

0

Methylene blue removal using raw and modified biomass Plumeria alba (white frangipani) in batch mode: isotherm, kinetics, and thermodynamic studies. Hazardous dyes used in textile industries are considered high-risk pollutants to the environment. The raw as well as acid-treated Plumeria alba (white frangipani) leaf powder (WFLP and SWFLP) were used for the adsorption of methylene blue (MB) that is available in industrial wastewaters following the batch adsorption technique. The characterizations of adsorbents were done by FTIR, SEM, EDX, TGA, and zeta potential parameters. The adsorption was considered for the effects of temperature, initial dye concentration, solution pH, adsorbent dosage, and contact time. The experimental results obtained in the adsorption of MB were examined by nonlinear error functions like chi-square (χ 2 ), ARE, and MPSD for three isotherm models: Langmuir, Freundlich, and Temkin. The maximum monolayer adsorption capacity, q max (mg/g), was 45.45 mg/g for raw WFLP and 250 mg/g for SWFLP. The adsorbents fitted to the pseudo-second-order kinetic model (R 2 = 0.99) using the experimental data of batch adsorption. The thermodynamic studies explained the spontaneity and nature of adsorption for raw and acid-treated adsorbents. The batch experimental results and characterizations of the adsorbents revealed that the selected adsorbents would be the best adsorbents for the removal of MB from the wastewater solution.

0

1

0

1

0

1

0

1

0

Initial Experience With the NICO Myriad Device for Minimally Invasive Endoscopic Evacuation of Intracerebral Hemorrhage. Intracerebral hemorrhage (ICH) is a devastating form of stroke for which there is no consensus treatment. Although open craniotomy has been explored as a surgical treatment option, multiple minimally invasive (MIS) techniques have been developed including endoscopic evacuation. An adjunctive aspiration device can be used through the working channel to provide an additional degree of freedom and increased functionality regarding clot manipulation and morcellation.

0

1

0

1

0

Mannosylerythritol lipids: production, downstream processing, and potential applications. Mannosylerythritol lipids (MELs) are biosurfactants produced by various fungal species. Depending on the degree of acetylation and further chemical modifications, these glycolipids can show remarkable biological properties, including the increase of water retention in the stratum corneum suppression of melanogenic enzymes tyrosinase-1 and -2, reversion of UV-A radiation-induced aquaporin-3 suppression, skin whitening, and anti-aging effects. These applications of MELs require high purity, which is usually reached by liquid-liquid extraction followed by chromatography, obtaining ≥95% purity. This worked aimed to critically discuss the current state of the art and trends on the production of MELs, including post-production treatment as enzymatic conversion. In addition, their application as skincare or pharmaceutical agents and agricultural biostimulants.

0

1

0

The cytokinin type-B response regulator PeRR12 is a negative regulator of adventitious rooting and salt tolerance in poplar. Adventitious root (AR) development is an ecologically and economically important biological process that maintains ecological balance, improves plant survivability, and allows for massive vegetative propagation, but its genetic mechanisms are not well understood. Here, eight Arabidopsis response regulator (ARR) genes were cloned and identified in poplar, most of which were detected in the AR, phloem, and xylem and showed remarkable induction at different time points during AR development. Subcellular localization indicated that most of these PeRR genes are in the nucleus. Based on qRT-PCR expression analysis of some genes related to AR development, we inferred that overexpression of PeRR12 (OE_PeRR12) may inhibited AR formation by suppressing the transcription of PeWOX11, PeWOX5, PePIN1 and PePIN3 in poplar while promoting type-A RR transcripts. Correspondingly, exogenous auxin partially restored the rooting of OE_PeRR12 poplar by inhibiting PeRR12 expression. Moreover, the activities of the antioxidant systems of OE_PeRR12 poplars were lower than those of wild-type poplars under salt stress conditions, indicating that PeRR12 may acts as a repressor that mediates salt tolerance by suppressing the expression of PeHKT1;1. Altogether, these results suggest that PeRR12 plays essential roles in mediating AR formation and salinity tolerance in poplar.

0

1

0

Demonstration of mucus simulant clearance in a Bench-Model using acoustic Field-Integrated Intrapulmonary Percussive ventilation. Intrapulmonary Percussive Ventilation (IPV) is a high-frequency airway clearance technique used to help in mucus transport for mechanically ventilated and unventilated patients. Despite the many years of usage, this technique does not provide clear evidence of its intended efficacy. This is mainly attributable to the lack of in vitro observations that show "mucokinesis" towards the direction of the mouth. In the current manuscript, we demonstrate and subsequently propose a mechanism that details the movement of a mucus simulant in the proximal (towards the mouthpiece) direction. Towards this end, a novel method utilizing a high-frequency acoustic field in addition to the conventional air pulsations brought forth by traditional IPV is proposed. Under these conditions, at certain parameter settings, it is shown that the simulant is broken down into much smaller parts and subsequently pushed in the upstream direction gradually over a period of half-hour.

0

1

0

1

0

Sclerostin ablation prevents aortic valve stenosis in mice. The objective of this study was to test the hypothesis that targeting sclerostin would accelerate the progression of aortic valve stenosis. Sclerostin (mouse gene, Sost ) is a secreted glycoprotein that acts as a potent regulator of bone remodeling. Antibody therapy targeting sclerostin is approved for osteoporosis but results from a stage III clinical trial showed multiple off-target cardiovascular effects. Wild-type (WT, Sost +/+ ) and Sost -gene knockout-expression (Null, Sost -/- ) mice were generated and maintained to 12 mo of age on a high-cholesterol diet to induce aortic valve stenosis. Mice were examined by echocardiography, histology, and RNAseq. Immortalized valve interstitial cells were developed from each genotype for in vitro studies. Null mice developed a bone overgrowth phenotype, similar to patients with sclerosteosis. Surprisingly, however, WT mice developed hemodynamic signs of aortic valve stenosis, whereas Null mice were unchanged. WT mice had thicker aortic valve leaflets and higher amounts of α-smooth muscle actin, a marker myofibroblast activation and dystrophic calcification, with very little evidence of Runx2 expression, a marker of osteogenic calcification. RNAseq analysis of aortic roots indicated the HOX family of transcription factors was significantly upregulated in Null mice, and valve interstitial cells from Null animals were enriched with Hoxa1, Hoxb2, and Hoxd3 subtypes with downregulated Hoxa7. In addition, Null valve interstitial cells were shown to be less contractile than their WT counterparts. Contrary to our hypothesis, sclerostin targeting prevented hallmarks of aortic valve stenosis and indicates that targeted antibody treatments for osteoporosis may be beneficial for these patients regarding aortic stenosis. NEW & NOTEWORTHY We have found that genetic ablation of the Sost gene (protein: sclerostin) prevents aortic valve stenosis in aged, Western diet mice. This is a new role for sclerostin in the cardiovascular system. To the knowledge of the authors, this is one of the first studies directly manipulating sclerostin in a cardiovascular disease model and the first to specifically study the aortic valve. We also provide a potential new role for Hox genes in cardiovascular disease, noting pan- Hox upregulation in the aortic roots of sclerostin genetic knockouts. The role of Hox genes in postnatal cardiovascular health and disease is another burgeoning field of study to which this article contributes.

0

1

0

Timing and duration of stopovers affects propensity to breed, incubation periods, and nest success of different wintering cohorts of red knots in the Canadian Arctic during the Years 2009 to 2016. Recent interest in migratory connectivity of shorebirds leads to examining the role stopovers and connectivity play in reproductive success. Since many shorebird species are declining, there is a need to determine factors affecting reproductive success. We used light records from 104 geolocators recovered from red knots (Calidris canutus rufa) to examine-incubation success as a function of temporal patterns at stopovers, year (2009-2016), and wintering cohort. Geolocators were attached on leg flags, mainly in Delaware Bay (New Jersey) and Texas. Successful incubation in different years ranged from 21 to 76%; from 8 to 43% of knots did not attempt incubation on breeding grounds. This is the first estimate of the number of shorebirds going to the Arctic that did not breed, since all other estimates of success were derived from field studies based on birds that initiated nests. High breeding success (76%) occurred in only one year (2011). Nearly all of knots stopped in Hudson Bay region. Arrival date and time in the Pre-Arctic, arrival on breeding grounds, year, and wintering cohort were associated with successful incubation. The percentage attempting incubation, and the percentage that were successful, varied by wintering cohort. When only the east coast rufa knots are considered, time spent on Delaware Bay showed a significant duration difference. Knots wintering in Texas had the highest propensity to initiate incubation (96%), and the highest incubation success (67%). Of rufa knots using the Atlantic flyway, those wintering in southern South America had the lowest incubation success rate (25%). We discuss the importance of quality of flyways, opportunities for refuelling during migration, and importance of time at stopovers. These data can be used to understand migratory connectivity, distinguish factors affecting reproductive success of long-distance migrants, determine which parts of the annual cycle require protection, and aid in recovery plans for long-distance migrants.

0

1

0

1

0

Cell wall synthesis and remodelling dynamics determine division site architecture and cell shape in Escherichia coli. The bacterial division apparatus catalyses the synthesis and remodelling of septal peptidoglycan (sPG) to build the cell wall layer that fortifies the daughter cell poles. Understanding of this essential process has been limited by the lack of native three-dimensional views of developing septa. Here, we apply state-of-the-art cryogenic electron tomography (cryo-ET) and fluorescence microscopy to visualize the division site architecture and sPG biogenesis dynamics of the Gram-negative bacterium Escherichia coli. We identify a wedge-like sPG structure that fortifies the ingrowing septum. Experiments with strains defective in sPG biogenesis revealed that the septal architecture and mode of division can be modified to more closely resemble that of other Gram-negative (Caulobacter crescentus) or Gram-positive (Staphylococcus aureus) bacteria, suggesting that a conserved mechanism underlies the formation of different septal morphologies. Finally, analysis of mutants impaired in amidase activation (ΔenvC ΔnlpD) showed that cell wall remodelling affects the placement and stability of the cytokinetic ring. Taken together, our results support a model in which competition between the cell elongation and division machineries determines the shape of cell constrictions and the poles they form. They also highlight how the activity of the division system can be modulated to help generate the diverse array of shapes observed in the bacterial domain.

0

1

0

1

0

1

0

Biomarkers of nanomaterials hazard from multi-layer data. There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identify mRNA-based toxicity markers and extensively replicate them in multiple independent datasets. We find that models based on combinations of omics-derived features and material intrinsic properties display significantly improved predictive accuracy as compared to physicochemical properties alone.

0

1

0

A MEG compatible, interactive IR game paradigm for the study of visuomotor reach-to-target movements in young children and clinical populations: The Target-Touch Motor Task. The conventional focus on discrete finger movements (i.e., index finger flexion or button-box key presses) has been an effective method to study neuromotor control using magnetoencephalography (MEG). However, this approach is challenging for young children and not possible for some people with physical disability.

0

1

0

1

0

1

0

Variability in Intensive Care Utilization for Intracerebral Hemorrhage in the United States: Retrospective Cohort Study. There are urban-rural geographic health disparities in intracerebral hemorrhage (ICH) outcomes. However, there is limited data regarding the relationship between intensive care (ICU) availability and ICH outcomes. We examined whether ICU availability was a significant contributor to ICH outcomes by US geographic region.

0

1

0

1

0

1

0

1

0

Visualizing RNA polymers produced by hot wet-dry cycling. It is possible that the transition from abiotic systems to life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers and polymers. The aim of the study reported here was to verify this claim and visualize the products prepared from solutions composed of single mononucleotides and 1:1 mixture of two mononucleotides. Therefore, we designed experiments that allowed comparisons of all such mixtures representing six combinations of the four mononucleotides of RNA. We observed irregular stringy patches and crystal strands when wet-dry cycling was performed at room temperature (20 °C). However, when the same solutions were exposed to wet-dry cycles at 80 °C, we observed what appeared to be true polymers. Their thickness was consistent with RNA-like products composed of covalently bonded monomers, while irregular strings and crystal segments of mononucleotides dried or cycled at room temperature were consistent with structures assembled and stabilized by weak hydrogen bonds. In a few instances we observed rings with short polymer attachments. These observations are consistent with previous claims of polymerization during wet-dry cycling. We conclude that RNA-like polymers and rings could have been synthesized non-enzymatically in freshwater hot springs on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.

0

1

0

1

0

Intraoral Styloidectomy Using an Endoscope With Tissue Retractor. The extraoral approach with the risk of facial nerve injury and the visible scar is commonly performed for an elongated styloid process, because intraoral styloidectomy is challenging for the deep and limited surgical field. The authors report minimally invasive intraoral styloidectomy using an endoscope with tissue retractor. A 57-year-old female was referred to our department with a left pharyngeal foreign body sensation and pharyngeal pain after head turning and neck compression. Clinical and radiological diagnosis was an elongated styloid process (Eagle syndrome). Because the styloid process could be palpated intraorally, the patient underwent endoscopically-assisted intraoral styloidectomy without tonsillectomy under general anesthesia as minimally invasive surgery. The styloid process was resected safely with a piezoelectric surgical device under endoscopic guidance. The postoperative course was uneventful without complications.

0

1

0

Accurate measurements of self-diffusion coefficients with benchtop NMR using a QM model-based approach. The measurement of self-diffusion coefficients using pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) spectroscopy is a well-established method. Recently, benchtop NMR spectrometers with gradient coils have also been used, which greatly simplify these measurements. However, a disadvantage of benchtop NMR spectrometers is the lower resolution of the acquired NMR signals compared to high-field NMR spectrometers, which requires sophisticated analysis methods. In this work, we use a recently developed quantum mechanical (QM) model-based approach for the estimation of self-diffusion coefficients from complex benchtop NMR data. With the knowledge of the species present in the mixture, signatures for each species are created and adjusted to the measured NMR signal. With this model-based approach, the self-diffusion coefficients of all species in the mixtures were estimated with a discrepancy of less than 2 % compared to self-diffusion coefficients estimated from high-field NMR data sets of the same mixtures. These results suggest benchtop NMR is a reliable tool for quantitative analysis of self-diffusion coefficients, even in complex mixtures.

0

1

0

1

0

1

0

Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. With the introduction of immunotherapy, significant improvement has been made in the treatment of head and neck squamous cell carcinoma (HNSCC). However, only a small subset of patients with HNSCC benefit from immunotherapy. The current biomarker, a programmed cell death protein ligand 1 (PD-L1) expression that is widely used in treatment decision making for advanced HNSCC, has only a moderate predictive value. Additionally, PD-L1-based assay has critical inherent limitations due to its highly dynamic nature and lack of standardization. With the advance in molecular techniques and our understanding of biology, more reliable, reproducible, and practical novel biomarkers are being developed. These include but are not limited to neoantigen/mutation characteristics, immune transcriptomes, tumor-infiltrating immune cell composition, cancer epigenomic, proteomics and metabolic characteristics, and plasma-based and organoid assays.

0

1

0

1

0

1

0

1

0

Roles of estrogens, estrogen-like compounds, and endocrine disruptors in adipocytes. Women are subject to constitutional changes after menopause, which increases conditions and diseases prone to cardiovascular risks such as obesity and diabetes mellitus. Both estrogens and androgens influence the individual's metabolic mechanism, which controls the fat distribution and the hypothalamic organization of the regulatory centers of hunger and satiety. While androgens tend to accumulate fat in the splanchnic and the visceral region with an increase in cardiovascular risk, estrogens generate more subcutaneous and extremity distribution of adipose tissue. The absence of estrogen during menopause seems to be the main factor that gives rise to the greater predisposition of women to suffer cardiovascular alterations. However, the mechanisms by which estrogens regulate the energy condition of people are not recognized. Estrogens have several mechanisms of action, which mainly include the modification of specific receptors that belong to the steroid receptor superfamily. The alpha estrogen receptors (ERα) and the beta receptors (ERβ) have a fundamental role in the metabolic control of the individual, with a very characteristic corporal distribution that exerts an influence on the metabolism of lipids and glucose. Despite the significant amount of knowledge in this field, many of the regulatory mechanisms exerted by estrogens and ER continue to be clarified. This review will discuss the role of estrogens and their receptors on the central regulation of caloric expenditure and the influence they exert on the differentiation and function of adipocytes. Furthermore, chemical substances with a hormonal activity that cause endocrine disruption with affectation on estrogen receptors will be considered. Finally, the different medical therapies for the vasomotor manifestations of menopause and their role in reducing obesity, diabetes, and cardiovascular risk will be analyzed.

0

1

0

1

0

1

0

1

0

1

0

1

0

Fall-from-Height Detection Using Deep Learning Based on IMU Sensor Data for Accident Prevention at Construction Sites. Workers at construction sites are prone to fall-from-height (FFH) accidents. The severity of injury can be represented by the acceleration peak value. In the study, a risk prediction against FFH was made using IMU sensor data for accident prevention at construction sites. Fifteen general working movements (NF: non-fall), five low-hazard-fall movements, (LF), and five high-hazard-FFH movements (HF) were performed by twenty male subjects and a dummy. An IMU sensor was attached to the T7 position of the subject to measure the three-axis acceleration and angular velocity. The peak acceleration value, calculated from the IMU data, was 4 g or less in general work movements and 9 g or more in FFHs. Regression analysis was performed by applying various deep learning models, including 1D-CNN, 2D-CNN, LSTM, and Conv-LSTM, to the risk prediction, and then comparing them in terms of their mean absolute error (MAE) and mean squared error (MSE). The FFH risk level was estimated based on the predicted peak acceleration. The Conv-LSTM model trained by MAE showed the smallest error (MAE: 1.36 g), and the classification with the predicted peak acceleration showed the best accuracy (97.6%). This study successfully predicted the FFH risk levels and could be helpful to reduce fatal injuries at construction sites.

0

1

0

Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort. Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death.

0

1

0

1

0

1

0

1

0

1

0

Acid-sensing ion channel 1: potential therapeutic target for tumor. Acidic extracellular pH is a major characteristic of tumor tissue, studies suggest that the local pH value of malignant tumor tissues is between 6.0 and 6.9. Acid-sensing ion channel 1 (ASIC1) is proton-gated cation channel activated by low extracellular pH, recently an increasing number of studies have suggested that ASIC1 is involved in different kinds of tumors, which plays an important role in the occurrence and development of tumors. Therefore, this review will summarize studies involved in ASIC1 on tumors and discuss the effect and mechanism of ASIC1 in numerous related tumors, which will provide new perspectives for tumor therapeutic targets.

0

1

0

1

0

1

0

Long-Term Follow-Up on Morbidity Among Women With a History of Gestational Diabetes Mellitus: A Systematic Review. Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases.

0

1

0

A new chiral stationary phase based on noscapine: Synthesis, enantioseparation, and docking study. Noscapine is an isolated compound from the opium poppy, with distinctive chiral structure and chemistry, interacts with other compounds due to having multiple π-acceptors, hydrogen bond acceptors, and ionic sites. Therefore, it has promising applicability for the enantioselective separation of a wide range of polar, acidic, basic, and neutral compounds. A new noscapine derivative chiral stationary phase (ND-CSP) has been synthesized by consecutive N-demethylation, reduction, and N-propargylation of noscapine followed by attachment of a solid epoxy-functionalized silica bed through the 1,3-dipolar Huisgen cycloaddition. The noscapine derivative-based stationary phase provides a considerable surface coverage, which is greater than some commercial CSPs and can validate better enantioresolution performance. The major advantages inherent to this chiral selector are stability, reproducibility after more than 200 tests, and substantial loading capacity. The characterization by Fourier transform infrared (FTIR) spectroscopy and elemental analysis indicated successful functionalization of the silica surface. Chromatographic method conditions like flow rate and mobile phase composition for enantioseparation of various compounds such as warfarin, propranolol, mandelic acid, and a sulfanilamide derivative were optimized. Comparing the experimental results with docking data revealed a clear correlation between the calculated binding energy of ND-CSP and each enantiomer with the resolution of enantiomer peaks.

0

1

0

1

0

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic. As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology.

0

1

0

1

0

1

0

: Short-term effects of exposure to particulate matter on hospital admissions for asthma and chronic obstructive pulmonary disease. We investigated the effects of particulate matter (PM) factors on hospitalization rates for asthma and chronic obstructive pulmonary disease (COPD). We obtained data on pollutants-PM10, PM2.5-in Seoul, South Korea. We also investigated data for asthma and COPD exacerbation that required hospitalization from 2006 to 2016. We used a time-stratified case-crossover design and generalized additive models with log transformation to assess adjusted risk, and conditional logistic regression was performed to analyze these data. Our study showed that PM10 and PM2.5, on different best lag days, were associated with increased risks of COPD or asthma hospitalization. The odds ratios (ORs) for each per-unit increase in PM10 and PM2.5 were higher in patients with male asthma (PM10: OR, 1.012; 95% confidence interval [CI], 1.008-1.016 and PM2.5: OR, 1.015; 95% CI, 1008-1.023), preschool asthma (PM10: OR, 1.015; 95% CI, 1.006-1.015 and PM2.5: OR, 1.015; 95% CI, 1.009-1.024), male COPD (PM10: OR, 1.012; 95% CI, 1.005-1.019 and PM2.5: OR, 1.013; 95% CI, 1.000-1.026), and senior COPD (PM10: OR, 1.016; 95% CI, 1.008-1.024 and PM2.5: OR, 1.022; 95% CI, 1.007-1.036). Increasing PM levels increased hospitalizations for asthma and COPD. Additionally, the consequences may be different according to age and sex, and PM2.5 may have a more significant effect on airway disease patients than PM10.

0

1

0

1

0

Adherence to Mediterranean Diet in Croatia: Lessons Learned Today for a Brighter Tomorrow. Non-communicable diseases (NCD) and lifestyle, particularly diet, have a close relationship. Based on the recent statistics, Croatian men and women lead in European overweight lists, which implies pessimistic prognosis in terms of incidence and prevalence of NCDs in the future. One of the possible solutions to overcome weight problems is turn to traditional balanced and sustainable diets, such as the Mediterranean diet. In this study, we assessed adherence towards Mediterranean diet using a validated questionnaire in an online survey and associated adherence scores with several demographic and anthropometric data. Based on the results of a validated Mediterranean Diet Adherence Screener (N = 3326), we assessed the adherence score to be 7.6 ± 2.5. The score tended to depend on sex, residence, age, education, income, and body mass index (BMI); indeed, women, residents of a coastal part of the country, older volunteers, those possessing a higher education degree, those with higher income, and those with lower BMI were associated with higher scores. As income was one of the significant findings related to higher adherence scores, we developed a dietary plan complying with Mediterranean diet principles that, on average, costed less than the average traditional balanced diet menu. Taken together, this study brought new findings regarding target groups who need to be encouraged to make lifestyle changes, and highlighted the first steps on how to make them.

0

1

0

Intelligent Reconstruction Algorithm-Based Computed Tomography Images for Automatic Detection of Gastric Tumor. The aim of this study was to explore the application of computed tomography (CT) images in the diagnosis of gastric tumor under the intelligent reconstruction algorithm (IRA). 120 patients with gastric cancer were selected and all the patients underwent CT scanning, and CT images were analyzed based on the Feldkamp-Davis-Kress algorithm (FDK algorithm) to evaluate the imaging features of gastric lesions. According to biopsy or surgical pathology, the detection rate of CT images was calculated. The results showed that there were three pathological types of benign tumors (polyps, leiomyomas, and mesenchymomas) and three pathological types of malignant tumors (mesenchymomas, adenomas, and lymphomas). In addition, the detection rates of CT scans were different, reaching 94.2% on different orientations of the stomach, 90.7% of benign tumors, and 90.9% of malignant tumors, so the detection rate of different orientations was relatively high. CT images based on the FDK IRA could realize a high detection rate in diagnosis, accurately locate the lesion, and display the characteristics of the lesion and the metastasis of surrounding tissues; there were significant differences between benign and malignant gastric tumors in CT images, and the detection effect was obvious, which is worthy of clinical application and promotion.

0

1

0

Uncovering the dynamic effects of DEX treatment on lung cancer by integrating bioinformatic inference and multiscale modeling of scRNA-seq and proteomics data. Lung cancer is one of the leading causes of cancer-related death, with a five-year survival rate of 18%. It is a priority for us to understand the underlying mechanisms affecting lung cancer therapeutics' implementation and effectiveness. In this study, we combine the power of Bioinformatics and Systems Biology to comprehensively uncover functional and signaling pathways of drug treatment using bioinformatics inference and multiscale modeling of both scRNA-seq data and proteomics data. Based on a time series of lung adenocarcinoma derived A549 cells after DEX treatment, we first identified the differentially expressed genes (DEGs) in those lung cancer cells. Through the interrogation of regulatory network of those DEGs, we identified key hub genes including TGFβ, MYC, and SMAD3 varied underlie DEX treatment. Further gene set enrichment analysis revealed the TGFβ signaling pathway as the top enriched term. Those genes involved in the TGFβ pathway and their crosstalk with the ERBB pathway presented a strong survival prognosis in clinical lung cancer samples. With the basis of biological validation and literature-based curation, a multiscale model of tumor regulation centered on both TGFβ-induced and ERBB-amplified signaling pathways was developed to characterize the dynamic effects of DEX therapy on lung cancer cells. Our simulation results were well matched to available data of SMAD2, FOXO3, TGFβ1, and TGFβR1 over the time course. Moreover, we provided predictions of different doses to illustrate the trend and therapeutic potential of DEX treatment. The innovative and cross-disciplinary approach can be further applied to other computational studies in tumorigenesis and oncotherapy. We released the approach as a user-friendly tool named BIMM (Bioinformatic Inference and Multiscale Modeling), with all the key features available at https://github.com/chenm19/BIMM.

0

1

0

1

0

Pazopanib restricts small cell lung cancer proliferation via reactive oxygen species-mediated endoplasmic reticulum stress. Pazopanib is an approved multitarget anticancer agent for soft tissue sarcoma (STS) and renal cell carcinoma (RCC), which is also under clinical investigation for other malignancies, including small cell lung cancer (SCLC). However, the potential anti-SCLC mechanisms of pazopanib remain unclear.

0

1

0

Co-Infection of Oral Candida albicans and Porphyromonas gingivalis Is Associated with Active Periodontitis in Middle-Aged and Older Japanese People. Background and Objectives: Candida albicans can be detected in subgingival sites of patients with periodontitis. However, the association between oral Candida albicans and periodontitis has not been fully elucidated in Japanese adults. The aim of this study is to clarify the relationship between oral Candida albicans infection/co-infection of oral C. albicans and Porphyromonas gingivalis and periodontitis among middle-aged and older Japanese people. Materials and Methods: Eighty-six patients (mean age 70.4 years) who visited the Hiroshima University Hospital from April to September 2021 were investigated in this study. Oral swab samples were collected from the tongue surface. C. albicans and P. gingivalis DNA was detected by real-time PCR using specific DNA primer sets. C. albicans -positive participants were classified into two groups according to the presence or absence of intron insertion of C. albicans DNA by PCR analysis. Results: C. albicans was detected in 22 (25.6%) of the 86 patients. Patients in their 80s recorded a higher C. albicans -positive rate (35.3%) compared with other participants. However, there was no significant association between the C. albicans positivity rate and clinical parameters such as sex, age, systemic disease, denture use, or oral health status. Of the 22 C. albicans -positive participants, 10 participants (45.5%) had C. albicans with intron insertion; 70% of participants who had C. albicans with intron insertion exhibited ≥6 mm probing depth. C. albicans / P. gingivalis co-infection was found in 12 patients (14%). Importantly, binomial logistic regression analysis revealed that C. albicans / P. gingivalis co-infection was significantly associated with ≥6 mm periodontal pockets with bleeding on probing ( p = 0.02). Conclusions: Co-infection of C. albicans and P. gingivalis is involved in active periodontitis in middle-aged and older people.

0

1

0

Efficacy and Safety of Apatinib plus Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cancer: A Phase II Trial. Evidence for neoadjuvant chemotherapy combined with targeted therapy for locally advanced esophageal squamous cancer (ESCC) is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of apatinib combined with taxol and cisplatin (ATP) for locally advanced ESCC. All patients were cT3-4aN0-3 M0 (IIIb-IVa) stage, which were confirmed by histopathology. Apatinib was taken orally (425 mg/d) for two cycles, followed by one cycle of rest. Taxol was administered at 135 mg/m 2 intravenously on day 1, and cisplatin was administered at 20 mg/m 2 intravenously on day 1 to day 3. Radical ESCC resection was performed 4 weeks after ATP. The primary endpoint was pathological response rate (pCR). Secondary endpoints were pathologic response rate (MPR), disease-free survival (DFS), overall survival (OS), R0 resection rate, and safety profile. This trial was registered. We evaluated 41 patients for screening from Oct 2018 to July 2020, of whom 39 were enrolled in the study, with a median age of 65 years (range 49-75 years), and 29 (74.4%) were male. Among the 39 patients, 1 was considered unresectable by the multidisciplinary team due to tumor progression, and 38 patients underwent surgery eventually. The median follow-up was 22 months (range 5-29 months), and the follow-up rate was 100%. The 1-year and 2-year OS was 95% and 95%, and the 1-year and 2-year DFS was 85% and 82%, respectively. Thirty-eight (97.3%) successfully underwent R0 resection. Of the 38 evaluable patients, 9 (23.6%) were pCR, and 15 (39.5%) were MPR. The most common ATP-related AEs were nausea (76.9%), leucopenia (53.8%), neutropenia (51.2%) and vomit (51.2%), anemia (41.0%), and hypertension (25.6%). The most frequent grade 3-4 events included leucopenia (15.3%), neutropenia (15.3%), nausea (12.8%), vomit (12.8%), and hypertension (10.2%). No treatment-related death occurred. Neoadjuvant apatinib combined with taxol and cisplatin for locally advanced ESCC showed favorable activity and manageable safety.

0

1

0

1

0

Amyloid β, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer's Disease. The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aβ peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.

0

1

0

1

0

Effects of corn distillers grains with yeast bodies and manipulation of dietary cation and anion difference on production, nutrient digestibility, and gas emissions from manure in lactating cows. In a randomized complete block design, 40 lactating Holstein cows (average 98 d in milk and 41 kg/d of milk yield) were randomly assigned to 1 of 4 diets: (1) containing soybean meal as the major protein supplement (CON diet); (2) CON diet with high-protein dried corn distillers grains at 20% on a dry matter (DM) basis by replacing mainly soybean meal (DG diet); (3) DG diet except that high-protein dried corn distillers grains with yeast bodies (extracted after corn ethanol production) was used (DGY diet); or (4) DG diet supplemented with sodium bicarbonate and potassium carbonate to elevate the dietary cation and anion difference (DCAD; DG-DCAD diet). The DCAD of CON, DG, DGY, and DG-DCAD were 185, 62, 67, and 187 mEq/kg of DM, respectively. The experiment began with a 10-d covariate period and then cows were fed the experimental diets for 5 wk (2-wk diet adaptation and 3-wk data collection periods). Dry matter intake and milk yield were measured daily, and spot urine and fecal samples were collected in the last week of the experiment to measure nutrient digestibility; N, S, and P utilization and excretion; and in vitro NH 3 and H 2 S emissions from manure. All data were analyzed using the MIXED procedure of SAS (random effect: block; fixed effects: diets, repeated week, and interactions). During data collection, DM intake was not different among treatment groups, but milk yield tended to be lower (42.4 vs. 39.9 kg/d) for DG, DGY, and DG-DCAD versus CON, which could have been caused by decreases in organic matter and neutral detergent fiber digestibility. Milk protein yield tended to be lower (1.33 vs. 1.24 kg/d) for DG, DGY, and DG-DCAD versus CON. Milk fat yield was lower (1.26 vs. 1.55 kg/d) for DG and DGY versus CON, but that for DG-DCAD (1.43 kg/d) did not differ from CON. Similarly, energy-corrected milk was lower (38.0 vs. 43.3 kg/d) for cows on DG and DGY versus those on CON, but it did not differ between DG-DCAD (40.7 kg/d) and CON. Urinary and fecal N excretion were greater for DG, DGY, and DG-DCAD compared with CON due to greater dietary crude protein content and N intake. However, NH 3 emissions did not differ across treatments. Intakes of dietary P and S were greater for DG, DGY, and DG-DCAD, resulting in greater excretion of those in manure and greater H 2 S emissions from manure compared with CON. These data suggest that the negative effects of feeding distillers grains on production of lactating cows can be partly explained by a decrease in nutrient digestibility (milk yield) and excessive anion load (milk fat). The milk fat response to DG-DCAD suggests that milk fat depression observed with a diet with high content of distillers grains can be partially alleviated by supplementation of cations. In the current study, we observed no beneficial effects of DG containing yeast bodies.

0

1

0

1

0

Title/Abstract stringlengths 45 11.7k	T001 int64 0 1	T002 int64 0 1	T004 int64 0 1	T005 int64 0 1	T007 int64 0 1	T012 int64 0 1	T023 int64 0 1	T024 int64 0 1	T025 int64 0 1	T026 int64 0 1	T028 int64 0 1	T029 int64 0 1	T031 int64 0 1	T032 int64 0 1	T033 int64 0 1	T037 int64 0 1	T039 int64 0 1	T040 int64 0 1	T041 int64 0 1	T042 int64 0 1	T043 int64 0 1	T046 int64 0 1	T047 int64 0 1	T048 int64 0 1	T052 int64 0 1	T053 int64 0 1	T054 int64 0 1	T055 int64 0 1	T057 int64 0 1	T058 int64 0 1	T059 int64 0 1	T060 int64 0 1	T061 int64 0 1	T064 int64 0 1	T065 int64 0 1	T066 int64 0 1	T067 int64 0 1	T068 int64 0 1	T070 int64 0 1	T073 int64 0 1	T074 int64 0 1	T078 int64 0 1	T080 int64 0 1	T081 int64 0 1	T082 int64 0 1	T089 int64 0 1	T090 int64 0 1	T091 int64 0 1	T092 int64 0 1	T093 int64 0 1	T097 int64 0 1	T098 int64 0 1	T101 int64 0 1	T103 int64 0 1	T104 int64 0 1	T109 int64 0 1	T114 int64 0 1	T116 int64 0 1	T121 int64 0 1	T122 int64 0 1	T123 int64 0 1	T125 int64 0 1	T126 int64 0 1	T129 int64 0 1	T131 int64 0 1	T167 int64 0 1	T168 int64 0 1	T170 int64 0 1	T184 int64 0 1	T191 int64 0 1	T192 int64 0 1	T195 int64 0 1	T196 int64 0 1	T204 int64 0 1
Subphenotypes of acute kidney injury in adults. Acute kidney injury is a heterogeneous syndrome and as such is associated with multiple predisposing conditions and causes all of which affect outcomes. Such heterogeneity may conceal the potential benefit of therapies when generally applied to patients with acute kidney injury (AKI). The discovery of pathophysiology-based subphenotypes could be of benefit in allocating current and future therapies to specific groups.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genetic association of toxin production in the dinoflagellate Alexandrium minutum . Dinoflagellates of the genus Alexandrium are responsible for harmful algal blooms and produce paralytic shellfish toxins (PSTs). Their very large and complex genomes make it challenging to identify the genes responsible for toxin synthesis. A family-based genomic association study was developed to determine the inheritance of toxin production in Alexandrium minutum and identify genomic regions linked to this production. We show that the ability to produce toxins is inheritable in a Mendelian way, while the heritability of the toxin profile is more complex. We developed the first dinoflagellate genetic linkage map. Using this map, several major results were obtained: 1. A genomic region related to the ability to produce toxins was identified. 2. This region does not contain any polymorphic sxt genes, known to be involved in toxin production in cyanobacteria. 3. The sxt genes, known to be present in a single cluster in cyanobacteria, are scattered on different linkage groups in A. minutum . 4. The expression of two sxt genes not assigned to any linkage group, sxtI and sxtG , may be regulated by the genomic region related to the ability to produce toxins. Our results provide new insights into the organization of toxicity-related genes in A. minutum , suggesting a dissociated genetic mechanism for the production of the different analogues and the ability to produce toxins. However, most of the newly identified genes remain unannotated. This study therefore proposes new candidate genes to be further explored to understand how dinoflagellates synthesize their toxins.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Mask-Wearing Perception of Preschool Children in Korea during the COVID-19 Pandemic: A Cross-Sectional Study. As the COVID-19 pandemic continues, wearing a mask has become a daily routine in Korea over the last two years. This study aims to investigate the mask-wearing perception of preschoolers (ages 4-6). The questionnaire comprised 17 yes-no closed-ended questions and two open-ended questions, and interviews of the children were conducted from January to February 2022, 15 months after mandatory mask wearing. Results showed that children were aware of the need to wear a mask to protect themselves and others from the coronavirus, and they perceived it as necessary and a good thing. Most children responded that they did not feel uncomfortable wearing a mask at preschool. This perception was thought to be influenced by the caregivers' perceptions of the mask in Korea. The way in which 4-5-year-olds perceived the mask differed from the way 6-year-olds did. Children aged between four and five seemed to perceive the mask as a physical self, while children aged six did not. As children who have experienced COVID-19 are growing up, attention is being focused on how the experience of wearing a mask affects their early childhood development.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Development and Verification of a Combined Diagnostic Model for Sarcopenia with Random Forest and Artificial Neural Network. Sarcopenia is a chronic disease characterized by an age-related decline in skeletal muscle mass and function, and diagnosis is challenging owing to the lack of a clear "gold standard" assessment method.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tree nut-induced anaphylaxis in Canadian emergency departments: Rate, clinical characteristics, and management. Data are sparse regarding tree nut-induced anaphylaxis (TNA).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Bioactive characterization of ultrasonicated ginger (Zingiber officinale) and licorice (Glycyrrhiza Glabra) freeze dried extracts. Ginger (Zingiber officinale) and Licorice (Glycyrrhiza glabra L.) are one of the most popular spices having a wide range of bioactive compounds that have varied biological and pharmacological properties. The study was aimed to extract polyphenols from Himalayan medicinal herbs ginger and licorice in different solvents using ultra-sonication technique. The extraction efficiency (EE) was determined, and the extracts were characterized for physical properties (particle size, colour values), total phenolics, flavonoids, antioxidant properties, and structural and morphological features. Ultra-sonicated ginger in aqueous phase had the highest EE of polyphenols (15.27%) as compared to other solvents. Similar trend was observed in licorice with EE of 30.52 % in aqueous phase followed by ethanol: water (50: 50), and methanol: water (50:50) with 28.52% and 26.39%, respectively. The preliminary screening showed the presence of tannins, phenolics, flavonoids, saponins and carbohydrates, steroids and alkaloids in all the extracts. The phenolic and flavonoid content of dried ginger was found higher in ethanolic extracts compared to fresh ones as revealed by HPLC. Similarly, for licorice, the ethanolic fractions had the highest polyphenolic content. The representative samples of ginger (ethanol: water 75:25 and ethylacetate: water 75:25) and licorice (ethanol: water 70:30 and methanol: water 50:50) were studied for FESEM and particle size. The results showed the agglomerated extract micro-particles with a diameter of 0.5-10 µm and increased particle size (ginger: 547 and 766 nm), and (licorice: 450 and 566 nm). The findings could be beneficial for the advancement of ginger and licorice processing, for the comprehension of these herbs as a source of natural antioxidants in different food formulations.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Chest CT in the evaluation of child abuse - When is it useful? Indications for chest CT in evaluation of child abuse are unknown.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cluster B personality disorders and its associated factors among psychiatric outpatients in Southwest Ethiopia: institutional-based cross-sectional study. Diagnosis of co-occurring personality disorders, particularly the most comorbid cluster B personality disorders in psychiatric patients is clinically important because of their association with the duration, recurrence, and outcome of the comorbid disorders. The study aimed to assess the prevalence of cluster B personality disorders and associated factors among psychiatric outpatients in Jimma Medical Center.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
MRI-guided DBS of STN under general anesthesia for Parkinson's disease: results and microlesion effect analysis. The efficacy of the subthalamic nucleus (STN) stimulation for Parkinson's disease has been widely established. The microlesion effect (MLE) due to deep brain stimulation (DBS) electrode implantation has been reputed to be a good predictor for long-term efficacy of the procedure but its analysis in asleep implantation is still unclear. We thus analyzed MLE rate in our strategy of targeting the STN on MRI under general anesthesia and its correlation with our long-term results.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fractal features of soil grain-size distribution in a typical Tamarix cones in the Taklimakan Desert, China. Tamarix cones play key roles in preventing sand erosion and maintaining regional ecosystem stability. This study aimed to explore the characteristics of soil grain size distribution (GSD) in Tamarix cones across the Taklimakan Desert, verify the relationships between soil grain composition and the fractal dimension, and analyze the relationships between soil GSD and environmental factors. Soils of the Tamarix cones from 0 to 500 cm soil depth were sampled every 20 cm at four sites (Qiemo, Qira, Aral, and Tazhong) along the periphery to the hinterland of the Taklimakan Desert. A total of 300 soil samples were collected to measure soil grain sizes and soil properties. Soil grain size composition was dominated by silt and very fine sand, and the fraction of fine particles decreased and that of the coarse particles increased with soil depth, except for at Tazhong. This suggested that suspension-size particles are the main component of the soil GSD and decrease with the increasing depth in the profiles at the Tamarix cones. The soils were poorly and moderately poorly sorted. Kurtosis generally showed a mesokurtic peak, and the GSD was negatively skewed towards the coarser particles. The fractal dimensions of GSD decreased in the following order Qiemo (2.30) > Qira (2.07) > Aral (1.99) > Tazhong (1.96) because of the increase of coarse particles. The fractal dimension had a strong positive correlation with the clay and silt fractions, and a strong negative correlation with the sand fraction, indicating that the fractal dimension can reflect the characteristics of the soil GSD. The strong relationships between the fractal dimensions and selected soil properties indicate that the fractal dimension can not only quantify changes in soil properties, but also reflect the degree of desertification and degradation in the desert region. Considering the strong wind activities and different deposition sources in the Taklimakan Desert, this study provides a deep insight into the soil formation processes of Tamarix cones within extreme arid desert ecosystems.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Development and validation of a blood-based genomic mutation signature to predict the clinical outcomes of atezolizumab therapy in NSCLC. We designed this study to develop a blood-based genomic mutation signature (bGMS) model for predicting the efficacy of atezolizumab therapy in non-small cell lung cancer (NSCLC) in a non-invasive manner.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Fabrication of Ce-doped DUT-52 as a sorbent for dispersive solid phase extraction of estrogens in human urine samples. A cerium (Ce)-doped metal-organic framework composite (Ce/DUT-52) was prepared by using a solvothermal method and was explored as a sorbent for dispersive solid phase extraction (DSPE) of three estrogens (α-estradiol, estrone, and hexestrol) in human urine samples. After doping with Ce(III), Ce/DUT-52 exhibited more attractive features involving a higher specific surface area (774.7 m 2 g -1 ) and zeta potential (31.4 mV), which made it an efficient adsorbent for the separation and enrichment of estrogens. The factors influencing DSPE efficiency such as the adsorbent amount, extraction time, pH, NaCl concentration, elution solvent and elution volume were investigated in detail. Under the evaluated conditions, Ce/DUT-52 showed good reusability ( n = 6, RSDs ≤ 4.8%). Notably, the cofunction of electrostatic interaction, hydrophobic interaction, hydrogen bonding and π-π interaction might play major roles between estrogens and Ce/DUT-52. Finally, coupled with high-performance liquid chromatography (HPLC), a fast and sensitive method was established, which provided low limits of detection (1.5-2.0 ng mL -1 ), wide linear ranges (3-500 ng mL -1 ) and satisfactory recoveries (79.8-96.1%). The results demonstrated that Ce/DUT-52 had excellent adsorption ability to the targets and the developed method provided an alternative strategy for the determination of trace estrogens or other compounds with similar chemical structures in urine samples.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Self-reported daytime napping, daytime sleepiness, and other sleep phenotypes in the development of cardiometabolic diseases: a Mendelian randomization study. Sleep disorders are associated with an increased risk of cardiometabolic diseases in observational studies, but the causality remains unclear. In this study, we leveraged two-sample Mendelian randomization (MR) analyses to assess the causal associations of self-reported daytime napping, daytime sleepiness, and other sleep phenotypes with cardiometabolic diseases including ischaemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and Type 2 diabetes mellitus (T2DM).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
In vitro evaluation of zearalenone toxicity by comet assay. The aim of this study was to reveal the potentially genotoxic effect of zearalenone on bovine lymphocytes by comet assay in vitro. The bovine lymphocytes were exposed to various zearalenone concetrations (50; 10; 2; 0.4 and 0.08 ppm). The viability and DNA damage of lymphocytes was monitored after 2 h, 24 h, 48 h and 72 h. After 2 hours of zearalenone exposure, statistically significant DNA damage occurred at all tested concentrations of 0.08 ppm (12.2±1.25; p⟨0.05), 0.4 ppm (12.7±0.88; p⟨0.01), 2 ppm (12.0±0.51; p⟨0.01), 10 ppm (11.2±0.47; p⟨0.01) and at 50 ppm (14.2±0 61; p⟨0.001). Significantly greater DNA damage was also found after 24 h, 48 h and 72 h. The obtained results showed that zearalenone may induce DNA damage of the bovine lymphocytes.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Teaching Spanish using the pharmacists' patient care process. The Hispanic population of the United States now comprises the largest minority and is expected to increase. Student pharmacists must be prepared to care for this segment of the population. Efforts to learn medical Spanish will assist in these endeavors.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mechanistic Origin of Favorable Substituent Effects in Excellent Cu Cyclam Based HNO Sensors. HNO has broad chemical and biomedical properties. Metal complexes and derivatives are widely used to make excellent HNO sensors. However, their favorable mechanistic origins are largely unknown. Cu cyclam is a useful platform to make excellent HNO sensors including imaging agents. A quantum chemical study of Cu cyclams with various substitutions was performed, which reproduced diverse experimental reactivities. Structural, electronic, and energetic profiles along reaction pathways show the importance of HNO binding and a proton-coupled electron transfer mechanism for HNO reaction. Results reveal that steric effect is primary and electronic factor is secondary (if the redox potential is sufficient), but their interwoven effects can lead to unexpected reactivity, which looks mysterious experimentally but can be explained computationally. This work suggests rational substituent design ideas and recommends a theoretical study of a new design to save time and cost due to its subtle effect.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Clinical relevance of amyloid in prostate samples: a report on 40 patients. To describe the clinical findings in patients with incidental prostatic amyloidosis.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Maternal cadmium exposure impairs placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling. Cadmium is a ubiquitous environmental pollutant, which can increase the risk of preeclampsia. This study was designed to determine the mechanism of cadmium exposure during pregnancy impaired placental angiogenesis that was associated with the occurrence of preeclampsia. The effects of cadmium exposure on placental thyroid hormone receptor signaling were explored. JEG3 cells were treated with CdCl 2 (20 μM) and the Dio2 inhibitor, IOP (100 μM). Cadmium levels in maternal blood and placentae were increased in preeclampsia group. Placental angiogenesis of preeclampsia was decreased with decreased expression of PLGF and VEGF and increased expression of sFlt1. Meanwhile, the expression and nuclear translocation of thyroid hormone receptor α were decreased in preeclampsia placenta, as well as the expression of Dio2, but not the expression and nuclear translocation of thyroid hormone receptor β. Furthermore, we found that cadmium exposure downregulated the expression of thyroid hormone receptor α and Dio2, but not the expression of thyroid hormone receptor β in JEG3 cells. Also, we found that cadmium exposure decreased the expression of PLGF and VEGF and increased the expression of sFlt1 in JEG3 cells. IOP pretreatment decreased the expression of PLGF and increased the expression of sFlt1. In conclusion, our results elucidated that cadmium exposure would impair placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Research progress of microneedles in the treatment of melanoma. Melanoma is an aggressive malignancy deriving from melanocytes, which is characterized by high tendency of metastases and mortality rate. Current therapies for melanoma, like chemotherapy, immunotherapy and targeted therapy, have the problem of systemic exposure of drugs, which will lead to many side effects and premature degradation of drugs. The resulting low drug accumulation at the lesion limits the therapeutic effect on melanoma and makes the cure rate low. As an emerging drug delivery system, microneedles (MNs) can efficiently deliver drugs through the skin, increase the drug distribution in deeper tumor sites and minimize the leakage of therapeutic drugs into adjacent tissues, thus improving the therapeutic effect. In addition, compared with traditional drug delivery methods, MN-based drug delivery system has the advantages of simplicity, safety and little pain. So MNs can be developed for the treatment of melanoma, which can relieve the pain of patients and improve the survival rate. This review aims to introduce an update on the progress of MNs as an innovative strategy for melanoma, especially when MNs combining with different therapies against melanoma, such as chemotherapy, targeted therapy, immunotherapy, photothermal therapy (PTT), photodynamic therapy (PDT) and synergic therapy.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Antibiotic prescription practices amongst veterinarians in Nigeria. The high rate of antibiotic resistance constitutes a global threat to the continuous use of these drugs, because of increasing treatment failures. The aim of this study was to survey antibiotic prescription practices of veterinarians and the possible contribution to antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in Nigeria during the COVID era. This was a cross-sectional study that used a 33-question survey questionnaire administered to registered veterinarians in Nigeria. The study was both online survey and hard copy administered during the annual meeting of the veterinarians from July to October 2021. Descriptive statistics, bivariate analysis using Chi-square test were also done to analyze the results, while a two-tailed P-value of <0.05 at 95% confidence level was considered statistically significant. IBM SPSS Version 26 was used to analyze the data. A total of 172 respondents completed the online and hard copy questionnaire. Majority of the respondents engaged majorly in mixed veterinary practice (72.1%). A total of 53.5% were aware of the country's policy concerning antibiotic prescription, while majority (64.5%) do not do culture and sensitivity before antibiotic prescription. Majority (34.3%) felt that the risk of potential adverse drug reaction could affect their decision when choosing to prescribe an antibiotic to the owner. Majority (51.2%) felt that some antibiotics were over prescribed, while 26.7% opined that all antibiotics were appropriately prescribed. To improve antibiotic use and practice amongst veterinarians in Nigeria, dependence on laboratory services for antibiotic prescription, enforcement of national guidelines and monitoring of antibiotic prescription amongst the veterinarians is essential to curb over-prescription and strengthen antimicrobial stewardship.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Noncoding RNAs Emerging as Drugs or Drug Targets: Their Chemical Modification, Bio-Conjugation and Intracellular Regulation. With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Novel 11β-substituted estradiol conjugates: Transition from ERα agonizts to effective PROTAC degraders. Endocrine therapy is widely used in clinic for breast cancer treatment, but long-term treatment inevitably causes drug resistance. Most of endocrine therapy-resistant breast cancers continue to depend on ERα signaling for growth and survival. In this regard, small molecule-induced ERα degradation, i.e. proteolysis targeting chimeras (PROTACs), represents an effective strategy to overcome endocrine resistance. Herein, we describe the design, synthesis, and biological evaluation of novel ERα-targeting PROTACs, wherein a E3 ligase ligand was attached to the 11β-position of estradiol via various linkers. Our efforts have identified a potent ERα PROTAC 15b that achieved excellent ERα degradation activity (DC<sub>50</sub> = 67 nM) and induced comparable inhibition of cell growth to that of fulvestrant in MCF-7 cells. Besides, 15b displayed antagonistic effects in uterine cells and favorable physicochemical properties, making it as a good lead compound for further development as anti-breast agents.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0
TMT-based quantitative proteomic and physiological analyses on lotus plumule of artificially aged seed in long-living sacred lotus Nelumbo nucifera. Seed longevity is important for the maintenance of seed nutritional quality, vigor, and germination potential during storage. Sacred lotus is known as one of the longest living seeds in the world and their ability to maintain longevity has been widely investigated. In this study, a suitable controlled deterioration treatment (CDT) method was first established to evaluate the vigor loss of lotus plumule (LP), and then the Tandem Mass Tags (TMT)-based proteomic analysis was performed on LP from the CDT-treated seed to quantitatively and qualitatively analyze the protein profile dynamic. In total, 4002 proteins were successfully quantified, of them, 558 differently accumulated proteins (DAPs) were identified. Protein processing and RNA-related proteins were found more easily to be affected by CDT, which may directly result in seed vigor loss. Meanwhile, CDT resulted in remarkable up-regulation of numerous proteins related to antioxidation, photosynthesis, RNA and DNA stability, starch and sucrose mobilization, and cell membrane and wall stability, which potentially played key roles in maintaining the lotus seed vigor under CDT. Histological and physiological analyses were also performed to verify some proteome results. This study provided both fundamental data and new insights to further uncover the secret of lotus seed longevity. SIGNIFICANCE: Seed aging affects the seed quality and can result in direct economic losses. The exceptional longevity of sacred lotus seed has attracted extensive attention. In this study, an optimized CDT method was used to mimic the natural aging process of sacred lotus seed, and based on TMT-based quantitative proteomic analysis on the LP profile of CDT-treated seeds, a series of differentially accumulation of specific proteins (DEPs) were revealed related to CDT resistance. Correspondingly, the physiological state and histological structure of the LP along with the CDT were detected to verify the proteome data. This study provided comprehensive information for the molecular basis of lotus seed aging analysis and facilitate to screen seed longevity related proteins for other plant species.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Continuous clonidine infusion: an alternative for children on mechanical ventilation. This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the cumulative dose of other sedatives and the hemodynamic response.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function. Changing composition of the gut microbiome is an important component of the gut adaptation to various environments, which have been implicated in various metabolic diseases including obesity and type 2 diabetes, but the mechanisms by which the microbiota influence host physiology remain contentious. Here we find that both diets high in the fermentable fiber inulin and vertical sleeve gastrectomy increase intestinal expression and circulating levels of the anti-microbial peptide Reg3g. Moreover, a number of beneficial effects of these manipulations on gut function, energy balance, and glucose regulation are absent in Reg3g knockout mice. Peripheral administration of various preparations of Reg3g improves glucose tolerance, and this effect is dependent on the putative receptor Extl3 in the pancreas. These data suggest Reg3g acts both within the lumen and as a gut hormone to link the intestinal microbiome to various aspects of host physiology that may be leveraged for novel treatment strategies.	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Progress in research of population size estimation by network scale-up method]. Network scale-up method is an indirect population size estimation method based on social network theory. It is widely used in estimating the hidden population size because it does not need to contact the target population. In order to provide reference for the further application of this method, this paper summarizes the traditional network scale-up method, the progress of this method and its combination with new survey techniques.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Construction and Analysis of a ceRNA Network Related to Salt-Sensitivity Hypertensives. Salt-sensitivity hypertensives (SSH) are an independent risk factor for cardiovascular disease. However, the mechanism of SSH is not clear. This study is aimed at constructing a competing endogenous RNA (ceRNA) network related to SSH.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Bottom-up design of hydrogels for programmable drug release. Hydrogels are a promising drug delivery system for biomedical applications due to their biocompatibility and similarity to native tissue. Programming the release rate from hydrogels is critical to ensure release of desired dosage over specified durations, particularly with the advent of more complicated medical regimens such as combinatorial drug therapy. While it is known how hydrogel structure affects release, the parameters that can be explicitly controlled to modulate release ab initio could be useful for hydrogel design. In this review, we first survey common physical models of hydrogel release. We then extensively go through the various input parameters that we can exercise direct control over, at the levels of synthesis, formulation, fabrication and environment. We also illustrate some examples where hydrogels can be programmed with the input parameters for temporally and spatially defined release. Finally, we discuss the exciting potential and challenges for programming release, and potential implications with the advent of machine learning.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Direct recovery of Zn from wasted alkaline batteries through selective anode's separation. In the present study, a leaner process for recovering zinc from spent alkaline batteries is studied at a laboratory scale. Such process is part of a diagram, under development, that aims at maximizing the value of all the battery components while reducing the costs of treatment and the environmental footprint involved in recycling this waste. It starts by a physical and selective pre-treatment stage that separates the anode from the remaining components followed by neutral leaching (three washing cycles at room temperature, S/L ratio of 1/5 (w/v), magnetic stirring for 15 min and settling during 45 min), acid leaching of the washed solid (4 mol/L of sulphuric acid, S/L ratio of 1/3 (w/v), 120 min at room temperature under magnetic stirring) and, finally, electrowinning of zinc from the pregnant leach solution (100 mA/cm 2 , 120 min under slow magnetic stirring). By leaching the anode alone, it is possible to obtain a solution rich in zinc (86 g/L), with very low concentration of other metals (<0.08 g/L). Such solution was adequate for zinc electrowinning, allowing an average recovery rate of 58%, without applying any purification stages, at the same time regenerating sulphuric acid for its recirculation. In conclusion, the results demonstrate that a more specific physical pre-treatment stage is highly desirable to recycle spent alkaline batteries in order to reduce the number of stages involved and the overall complexity, thus, reducing the costs involved and the potential environmental impacts, while maintaining high recovery rates of zinc.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The histone methyltransferase SETD2 negatively regulates cell size. Cell size varies between cell types but is tightly regulated by cell intrinsic and extrinsic mechanisms. Cell size control is important for cell function, and changes in cell size are frequently observed in cancer. Here, we uncover a role for SETD2 in regulating cell size. SETD2 is a lysine methyltransferase and a tumor suppressor protein involved in transcription, RNA processing and DNA repair. At the molecular level, SETD2 is best known for associating with RNA polymerase II through its Set2-Rbp1 interacting (SRI) domain and methylating histone H3 on lysine 36 (H3K36) during transcription. Using multiple independent perturbation strategies, we identify SETD2 as a negative regulator of global protein synthesis rates and cell size. We provide evidence that overexpression of the H3K36 demethylase KDM4A or the oncohistone H3.3K36M also increase cell size. In addition, ectopic overexpression of a decoy SRI domain increased cell size, suggesting that the relevant substrate is engaged by SETD2 via its SRI domain. These data add a central role of SETD2 in regulating cellular physiology and warrant further studies on separating the different functions of SETD2 in cancer development.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0
Role of salts and solvents on the defibrillation of food dye "sunset yellow" induced hen egg white lysozyme amyloid fibrils. Several food dyes are known to induce amyloid fibrillation when interacting with proteins. Here, we studied the role of sunset yellow (SY) in the amyloid fibrillation of hen egg white lysozyme (HEWL) and characterized the changes using spectroscopy techniques. Turbidity results showed that SY dye induces aggregation in HEWL in concentrations dependent manner. The aggregation induced by SY dye is kinetically very fast, no lag phase was detected, and the kinetics process follows an isodesmic kinetics pathway. The SY-dye induce aggregates have cross-β secondary structure confirmed by far-UV CD measurements. The effect of salts and solvents was also seen on SY-induced aggregates. Turbidity, far-UV CD, and kinetics results suggest that certain concentrations of NaCl and (NH 4 ) 2 SO 4 solubilize the SY-induce amyloid fibrils, but (NH 4 ) 2 SO 4 is more effective. Similarly, solvents are also solubilized the SY-induces HEWL amyloid fibrillation but the order of defibrillation is as follows: Isopropanol> ethanol > methanol which signified that isopropanol is more effective than other solvents. The salts and solvents data suggest that the electrostatic, as well as hydrophobic interaction, is responsible for SY-induced amyloid fibrillation. These conformational changes should be examined, more seriously for the purpose of food safety.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
A Two-Workshop Collaborative, Integrated Scheduling Algorithm considering the Prescheduling of the Root-Subtree Processes. Aiming at the existing two-workshop integrated scheduling algorithm with the same equipment resources, a unified vertical or horizontal scheduling rule is used to sort all processes and ignore the vertical and horizontal characteristics of the associated process position in the process tree, which affects the scheduling results. A two-workshop collaborative, integrated scheduling algorithm considering the prescheduling of the Root-Subtree processes is proposed. The algorithm proposes a process conflict adjustment strategy for the horizontal equipment constraints. The same equipment Root-Subtree processes are sorted and loaded into the corresponding equipment queue through the vertical and horizontal prescheduling method in a single-workshop environment, and it combines with the schedulable process set to dequeue the first process of the queue. To enhance the flexibility of process scheduling, it proposes a process conflict adjustment strategy for the vertical process tree constraints in the two workshops to determine the processing workshop of the processes and the actual start time, which narrows the search comparison for schedulable processes. The example tests show that the algorithm not only excavates and utilizes the effectiveness of the vertical and horizontal characteristics of the process tree, but also considers the process migration time. Therefore, the effect is better and more practical.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Role of Autophagy in the Pathogenesis of Diabetes and Therapeutic Potential of Autophagy Modulators in the Treatment of Diabetes and Metabolic Syndrome. Autophagy is critically involved in the maintenance of intracellular nutrient homeostasis and organelle function. Dysregulated autophagy is likely to play a role in the development of metabolic disorders and diabetes because autophagy is critical in the rejuvenation of dysfunctional or stressed endoplasmic reticulum and mitochondria that play a crucial role in the development of diabetes. Indeed, systemic autophagy insufficiency led to the increased tissue lipid content, aggravated metabolic and finally more severe diabetes when metabolic stress was imposed, suggesting that autophagy insufficiency of dysfunction of lysosome, an effector organelle of autophagy, due to aging, genetic predisposition or environmental factors could be an underlying cause of diabetes. Conversely, autophagy enhancer could improve metabolic profile of obese mice by reducing tissue lipid content and ameliorating metabolic inflammation. Furthermore, clearance of human islet amyloid polypeptide (hIAPP) oligomer and amyloid that accumulate in pancreatic islets of > 90% of diabetes patients was also dependent on autophagy. Consistently, autophagy enhancer could improve glucose profile and β-cell function of transgenic mice expressing amyloidogenic hIAPP in pancreatic β-cells, which was accompanied by reduced accumulation of hIAPP oligomer or amyloid, ameliorated β-cell apoptosis and increased β-cell mass. These results suggest that autophagy enhancer could be a novel therapeutic modality against diabetes associated with lipid overload and human diabetes characterized by islet amyloid accumulation.	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Utility of standard diffusion-weighted magnetic resonance imaging for the identification of ischemic optic neuropathy in giant cell arteritis. This study assessed diffusion abnormalities of the optic nerve (ON) in giant cell arteritis (GCA) patients with acute onset of visual impairment (VI) using diffusion-weighted magnetic resonance imaging (DWI). DWI scans of GCA patients with acute VI were evaluated in a case-control study. Two blinded neuroradiologists assessed randomized DWI scans of GCA and controls for ON restricted diffusion. Statistical quality criteria and inter-rater reliability (IRR) were calculated. DWI findings were compared to ophthalmological assessments. 35 GCA patients (76.2 ± 6.4 years; 37 scans) and 35 controls (75.7 ± 7.6 years; 38 scans) were included. ON restricted diffusion was detected in 81.1% (Reader 1) of GCA scans. Localization of ON restricted diffusion was at the optic nerve head in 80.6%, intraorbital in 11.1% and affecting both segments in 8.3%. DWI discerned affected from unaffected ON with a sensitivity, specificity, positive and negative predictive value of 87%/99%/96%/96%. IRR for ON restricted diffusion was κ inter = 0.72 (95% CI 0.59-0.86). DWI findings challenged ophthalmologic diagnoses in 4 cases (11.4%). DWI visualizes anterior and posterior ON ischemia in GCA patients with high sensitivity and specificity, as well as substantial IRR. DWI may complement the ophthalmological assessment in patients with acute VI.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Family form of nephrogenic X-linked diabetes indiabetes]. There is a global trend towards an increase in the prevalence of diabetes insipidus. Symptoms of nephrogenic diabetes insipidus with X-linked inheritance appear in men, in women with heterozygous mutations, are characterized by an isolated symptom complex of polyuria, polydipsia, hypostenuria. In children, more often than in adults, with fluid restriction, a clinic of water-deficient dehydration develops with hypernatremia, hyperthermia, and plasma hyperosmolality. This manuscript presents a case of Nephrogenic diabetes insipidus, X-linked familial form in male patients.At the same time, in the family along the female line, the mother and grandmother also had an increased need for water, the use of minirin was ineffective. In the older brother and younger brother, clinical manifestations of diabetes insipidus in the form of severe thirst and polyuria were noted from infancy, after the examination, the diagnosis was made - diabetes insipidus and desmopressin was prescribed.Due to the lack of effect from the use of desmopressin, the analysis of exons and adjacent sections of the introns of the AQP2 and AVPR2 genes was carried out by PCR and subsequent direct sequencing. No mutations were found in the AQP2 gene. The hemizygous substitution S315I was found in the AVPR2 gene. The familial form X was confirmed - linked nephrogenic diabetes insipidus. A hypothiazide was recommended, against the background of constant intake of which only a slight positive trend is observed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England. The SARS-CoV-2 Omicron subvariant, BA.2, may be less severe than previous variants; however, confounding factors make interpreting the intrinsic severity challenging.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Clinical Features and Treatment of Intra-Tendinous Suture Reaction Following Achilles Tendon Repair Using Nonabsorbable Suture Material: A Retrospective Case Series Study. We aimed to investigate the clinical manifestations, radiological findings, and therapeutic outcome of treatment for patients with surgically confirmed foreign body reaction following an Achilles tendon repair using non-absorbable suture material. Eight consecutive patients who were confirmed as having an intra-tendinous suture foreign body reaction in the histopathological report were enrolled in this study. Medical records of all patients in terms of clinical and radiological features were retrieved. Also, the outcome of treatment was evaluated at a follow-up of at least 12 months. All the patients complained of pain and a palpable mass around a previous surgical site at mean 25.1 months (range, 4-72 months) after the initial surgery. Magnetic resonance imaging (MRI) or ultrasound were used to detect the lesion. All the patients underwent surgical excision of foreign body reaction tissue and primary repair using absorbable suture material. After the treatment, the wounds were healed completely in all, and the average FAOS (foot and ankle outcome score) was 91.32 at mean follow-up for 22.4 months. In conclusion, intra-tendinous suture reaction is a rare complication following an Achilles tendon repair using nonabsorbable suture material, but it can be treated adequately with only surgical excision of foreign body reaction tissue and primary repair using absorbable suture material.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cervical Joint Position Sense in Individuals With Type 2 Diabetes and Its Correlations With Glycated Hemoglobin Levels: A Cross-Sectional Study. This study aimed to compare cervical joint position sense (JPS) between individuals with type 2 diabetes (T2D) and healthy individuals and to assess the correlation between glycated hemoglobin (HbA1c) values and cervical JPS in individuals with T2D.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021. The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years † with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Internet-based imagery rescripting intervention for adult survivors of institutional childhood abuse in the former German Democratic Republic - a pilot study. <b>Background:</b> From 1949 to 1990, about 500,000 children and adolescents in the former German Democratic Republic (GDR) were placed in institutional care. Many of these individuals experienced physical and sexual abuse as well as general maltreatment. While this population group is in great need of psychosocial support, few low-threshold interventions aimed at the needs of adult survivors of institutional childhood abuse exist. <b>Objective:</b> This pilot study examines the efficacy of an internet-based imagery rescripting intervention in reducing psychopathological symptoms, within a population of survivors of institutional abuse from state childcare institutions, in the former GDR. Additionally, a case study is presented, depicting the treatment of a woman suffering from PTSD after having been institutionalised in the former GDR. <b>Method:</b> Participants received 10 internet-based writing assignments, based on the principles of imagery rescripting, specifically tailored to the needs of survivors of institutional childhood abuse in the GDR. The participants received personalised feedback on their assignments. Symptoms of posttraumatic stress disorder (PTSD), complex posttraumatic stress disorder (CPTSD), depression, and anxiety were assessed at pre- and post-treatment. <b>Results:</b> A total of 15 participants completed the intervention (mean age 56.2 years; 66.7% female). Paired <i>t</i>-tests showed a significant reduction of PTSD, CPTSD, depression, and anxiety symptoms. Large effect sizes were found for PTSD (<i>d </i>= 1.26), CPTSD (<i>d </i>= .97), depression (<i>d </i>= 1.08) and anxiety (<i>d </i>= 1.20). <b>Conclusion:</b> The results of this pilot study provide preliminary evidence for the efficacy and feasibility of the intervention in treating psychopathological symptoms in survivors of institutional abuse in the GDR. The case study additionally demonstrates the applicability of the intervention. A randomised controlled trial should be applied to further evaluate the intervention and its effects. <b>Trial registration:</b> German Clinical Trials Register identifier: DRKS00020266..	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Role of Blood-Brain Barrier Dysfunction in Mild Cognitive Impairment: a Scientometric and Visualization Analysis from 2000 to 2021. Mild cognitive impairment (MCI) is a pathological stage between normal cognitive aging and dementia. The blood-brain barrier (BBB) breakdown is emerging as an early biomarker of MCI. This study aimed to visually analyze the literatures related to MCI caused by BBB dysfunction in recent 20 years, systematically identify collaboration networks, track research trends, highlight current hot spots, and predict future frontiers in this field. The related literatures published from 2000 to 2021 were obtained from the Web of Science with the search term "mild cognitive impairment and (blood-brain barrier or neurovascular unit or neurovascular coupling)". VOSviewer software was used to present knowledge map, CiteSpace software was used to extract literature information and make tables, including the top most influential countries, authors, institutions, periodicals, keywords, and references. A total of 333 literatures were used for visual analysis. After 2013, the literatures in the field of BBB dysfunction-induced MCI showed an increased trend in terms of year of publication and quantity of material, with more than 40 publications published each year. USA, England, China, and Sweden cooperated closely. In terms of institutions, Harvard Med Sch ranked first in the number of papers published, followed by Mstricht Univ and Univ Washington. In terms of journals, three of the top five co-cited journals belonged to USA, the other two journals were Neurobiol Aging and J Alzheimers DIS, which were from England and Netherlands respectively. A total of 1752 authors were identified, with Abhay P Sagare the most published and Zlokovic BV the most cited. Keyword emergence detection analysis showed that inflammation, oxidative stress, and memory were new research hot spot in this field. Overall, the research on BBB dysfunction-induced MCI is booming. In the future, cooperation and communication between different countries and institutions should be strengthened.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Epigenetic modifications in metabolic memory: What are the memories, and can we erase them? Inherent and acquired abnormalities in gene regulation due to the influence of genetics and epigenetics (traits related to environment rather than genetic factors) underlie many diseases including diabetes. Diabetes could lead to multiple complications including retinopathy, nephropathy, and cardiovascular disease that greatly increase morbidity and mortality. Epigenetic changes have also been linked to diabetes-related complications. Genes associated with many pathophysiological features of these vascular complications (e.g., inflammation, fibrosis, and oxidative stress) can be regulated by epigenetic mechanisms involving histone posttranslational modifications, DNA methylation, changes in chromatin structure/remodeling, and noncoding RNAs. Intriguingly, these epigenetic changes triggered during early periods of hyperglycemic exposure and uncontrolled diabetes are not immediately corrected even after restoration of normoglycemia and metabolic balance. This latency in effect across time and conditions is associated with persistent development of complications in diabetes with prior history of poor glycemic control, termed as metabolic memory or legacy effect. Epigenetic modifications are generally reversible and provide a window of therapeutic opportunity to ameliorate cellular dysfunction and mitigate or "erase" metabolic memory. Notably, trained immunity and related epigenetic changes transmitted from hematopoietic stem cells to innate immune cells have also been implicated in metabolic memory. Hence, identification of epigenetic variations at candidate genes, or epigenetic signatures genome-wide by epigenome-wide association studies can aid in prompt diagnosis to prevent progression of complications and identification of much-needed new therapeutic targets. Herein, we provide a review of epigenetics and epigenomics in metabolic memory of diabetic complications covering the current basic research, clinical data, and translational implications.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Supporting students with sex chromosome aneuploidies in educational settings: Results of a nationwide survey. Children with sex chromosome aneuploidies (SCAs) are at an increased risk for neurocognitive and behavioral disorders that may interfere with academic success, including early developmental delays, learning disabilities, executive function problems, and social communication deficits. The present national survey aimed to update and extend our understanding of school supports and educational outcomes for students with these increasingly common genetic diagnoses. Parents of children with a diagnosed SCA, birth to 21 years, living in the United States (N = 248), responded to an electronic survey with questions focused on school support plans, academic accommodations, educational therapies, school completion, and perceptions of educator awareness of SCAs. Results revealed high rates of delayed kindergarten, grade retention in primary years, and educational support plans (IEPs = 71%; Section 504 Plans = 26%). A majority (73%) of respondents with children over age 18 years (N = 41) reported their children successfully completed high school, and nearly half (46%) pursued post-secondary education opportunities. Many parents reported their children's educators had little to no knowledge of SCA conditions, justifying a need to train teachers and policy makers in the unique educational needs of children and adolescents with SCAs. School psychologists should be aware of the frequent need for accommodations and individualized support plans in this population so they can support children and families by advocating for early and comprehensive evaluations and intervention plans.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Menaquinone-7 ameliorates cerebrovascular calcification-associated memory decline in aged mice. Menaquinone (MK)-7 is a vitamin K2 analog that functions as a cofactor of γ-glutamyl carboxylase involved in the activation of vitamin K (VK)-dependent proteins. The present study aimed to evaluate the effect of MK-7 on memory and cognitive function in aged C57BL/6 mice. Eighteen-month-old mice were raised for a further 4 months, fed on a standard or calcium-rich diet (3 % [w/w]), and were orally given MK-7 (40 and 400 μg/day/mouse) five times per week during the same period. The Morris water maze (MWM) test was performed at 19 and 22 months. The aged mice showed noticeable memory declines in the MWM test at all time points compared with 6-week-old mice, and this memory loss was significantly restored by the daily administration of high-dose MK-7 for 4 months. MK-7 administration also improved micro-computed tomography-based cerebrovascular calcification and aging-associated declines in growth arrest-specific 6, total and carboxylated matrix Gla proteins, and ganglioside levels in the brain of aged mice. It serologically reduced phosphorous levels in the blood, but not the urea, cholesterol, and calcium. Taken together, the long-term administration of MK-7 significantly improved age-related memory and cognitive impairments, possibly through inhibition of cerebrovascular calcification in aged mice, indicating that it can be used to develop new drugs for improving memory and cognitive function in older adults.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0
Spermidine Crosslinked Gellan Gum-Based "Hydrogel Nanofibers" as Potential Tool for the Treatment of Nervous Tissue Injuries: A Formulation Study. Aim of the work was to develop a potential neural scaffold, endowed with neuroprotective and neuroregenerative potential, to be applied at the site of nervous tissue injuries: nanofibers, consisting of gellan gum (GG), spermidine (SP) and gelatin (GL), were prepared via electrospinning. SP was selected for its neuroprotective activity and cationic nature that makes it an ideal GG cross-linking agent. GL was added to improve the scaffold bioactivity.	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The impact of daylight on suicide rates. Since Durkheim and Morselli found a spring peak in suicides in the late 19th century, researchers have presented possible explanations, including daylight variation, for this seasonal pattern. Our identification strategy exploits the idiosyncratic variation in daylight within Norwegian regions, arising from the country's substantial latitudinal range. We use full population data for a period of 45 years in a pre-registered research design. We find a small and non-significant relationship: One extra hour of daylight increases the suicide rate by merely 0.75 % (95 % CI: -0.4 % to 1.9 %).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The perceptions of dental hygiene students about an asynchronous oral biology course. Medical and dental schools have long-established pedagogical approaches to teacher-centred face-to-face learning. The 3-year baccalaureate dental hygiene (DH) program at the University of Alberta, which enrolls 42 students of diverse ages and experiences each year, is no exception. Oral Biology II (OBIOL 302) is an intermediate-level course in the DH program; it was moved to an asynchronous online format to manage the disruptions of the COVID-19 pandemic. This mixed-method study explores the factors affecting the dental hygiene student experience in this online, asynchronous learning environment.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Live birth after transfer of a single euploid vitrified-warmed blastocyst according to standard timing vs. timing as recommended by endometrial receptivity analysis. To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of unsuccessful frozen embryo transfers (FETs).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Current best estimates of beam quality correction factors for reference dosimetry of clinical proton beams. Objective . To review the currently available data on beam quality correction factors,kQ,for ionization chambers in clinical proton beams and derive their current best estimates for the updated recommendations of the IAEA TRS-398 Code of Practice. Approach . The reviewed data come from 20 publications from whichkQvalues can be derived either directly from calorimeter measurements, indirectly from comparison with other chambers or from Monte Carlo calculated overall chamber factors,fQ.For cylindrical ionization chambers, a distinction is made between data obtained in the centre of a spread-out Bragg peak and those obtained in the plateau region of single-energy fields. For the latter, the effect of depth dose gradients has to be considered. To this end an empirical model for previously published displacement correction factors for single-layer scanned beams was established, while for unmodulated scattered beams experimental data were used. From all the data, chamber factors,fQ,and chamber perturbation correction factors,pQ,were then derived and analysed. Main results . The analysis showed that except for the beam quality dependence of the water-to-air mass stopping power ratio and, for cylindrical ionization chambers in unmodulated beams, of the displacement correction factor, there is no remaining beam quality dependence of the chamber perturbation correction factorspQ.Based on this approach, average values of the beam quality independent part of the perturbation factors were derived to calculatekQvalues consistent with the data in the literature. Significance . The resulting data from this analysis are current best estimates ofkQvalues for modulated scattered beams and single-layer scanned beams used in proton therapy. Based on this, a single set of harmonized values is derived to be recommended in the update of IAEA TRS-398.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
First-ever Clinical Experience With Magnetic Resonance-based Lattice Radiotherapy for Treating Bulky Gynecological Tumors. Bulky gynecological tumors are a rare entity of large primary tumors, for which only a limited range of therapeutic options is available. Among these, when surgical approach is deemed unsuitable based on comorbidities and/or technical feasibility, radiotherapy is administered at low doses with palliative intent only. Aggressive treatment of such large primary tumors might significantly prolong patient survival and improve their quality of life by effectively delaying tumor progression to extra-pelvic sites. Lattice radiotherapy is a type of Spatially Fractionated Radiation Therapy, specifically devoted to treat and debulk large tumor masses, which are not candidates for normofractionated homogeneous high-dose radiotherapy schedules due to potential harmful dose-volume effects. The aim of this case study was to report on the feasibility of a Magnetic Resonance Imaging-based Lattice approach.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Iodine-Promoted Oxidative Cyclization of Methyl Azaarenes and α-Amino Ketones for One-Pot Synthesis of 2-Azaaryl-5-aryl Oxazoles. A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0
Synthesis of nuevamine and a cyano-chilenine analog via divergent C(sp 3 )-H bond functionalization of isoindolinone derivatives. Divergent C(sp 3 )-H bond functionalizations of isoindolinone derivatives were developed to synthesize nuevamine, a cyano-chilenine derivative, and two related analogs. A copper-catalyzed C-H cross-dehydrogenative coupling ( via cation formation) allowed the formation of a new C-C bond leading to the direct assembly of the isoindolo[1,2- a ]isoquinolinone tetracyclic system of the nuevamine. The syntheses of the cyano-chilenine derivatives were carried out by installing two nitrile groups under basic conditions ( via anion formation). Then, the isoindolobenzazepinic system of the chilenine skeleton was constructed by a Houben-Hoesch cyclization process. The present methodology has the advantage of not requiring the use of pre-functionalized substrates.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0
Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development. Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1 Tg ) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1 Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to host HLA-C genotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay between KIR/HLA immunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specific KIR/HLA-C combinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1 + individuals. Compared to 60 HIV-1 - controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C + and KIR3DL2 + NK cell sub-populations from HIV-1 + individuals was enlarged compared to HIV-1 - controls. Stratification along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1 + NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Management Strategy of Alzheimer's Patients under the Medical-Care Integration Model Based on Big Data Evaluation. In the context of the era of big data, the management of Alzheimer's patients has aroused widespread concern in the society. What should the elderly and people with dementia do and how the society should accommodate these special groups have aroused heated discussions in the society. The goal of the medical-nursing integration model is to realize the integrated model of medical care-nursing-rehabilitation-old care, and to better satisfy the needs by providing medical services, rehabilitation care, and health management. The medical needs of the elderly can help the elderly maintain a healthy state; the elderly care needs can be better met through elderly care services, and the burden on families and society can be reduced. With the advancement of the medical-care integration model, new solutions have been provided for the management of senile dementia patients. Therefore, under the medical-care integration model, this paper managed Alzheimer's patients based on the big data algorithm based on association rules and compared it with the management of Alzheimer's patients under the traditional model, and drew the following conclusions: compared with the management satisfaction of Alzheimer's patients under the traditional model, family members and patients' total satisfaction with nursing management under the medical-care integration model was greatly improved; compared with the management of Alzheimer's patients under the traditional model, the incidence of adverse events in the management of Alzheimer's patients under the medical-care integration model was greatly reduced, which was reduced to 17.6%; under the medical-care integration model, the anxiety and depression scores of the elderly patients with dementia decreased rapidly; under the medical-care integration model, the living ability of senile dementia patients has been greatly improved; the use of the medical-care integration model to manage senile dementia patients has greatly improved the sleep quality, mental quality, and quality of life of senile dementia patients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update. Ocular drug delivery is one of the most challenging endeavors among the various available drug delivery systems. Despite having suitable drugs for the treatment of ophthalmic disease, we have not yet succeeded in achieving a proper drug delivery approach with the least adverse effects. Nanotechnology offers great opportunities to overwhelm the restrictions of common ocular delivery systems, including low therapeutic effects and adverse effects because of invasive surgery or systemic exposure. The present review is dedicated to highlighting and updating the recent achievements of nano-based technologies for ocular disease diagnosis and treatment. While further effort remains, the progress illustrated here might pave the way to new and very useful ocular nanomedicines.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Science communication activities at research institutes in Brazil: Recent expansion on the way to professionalization. This study was designed to analyze the science communication activities geared towards the general public undertaken at Brazilian research institutes. We identified how often such activities are carried out and what human and financial resources are available for them. The results suggest that between the years 2013 and 2017 there was an increase in science communication by research institutes responsible for a wide range of activities. To communicate with the public, the 169 institutes studied tend to use traditional communication channels more than social media. However, most of them did not have designated communication teams, drawing on specialized personnel from their host institution. Although they do engage in intensive communication activities, Brazilian research institutes still lack more a structured approach to science communication.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Single-Photon Emission Computed Tomographic Reverse Lymphatic Mapping for Groin Vascularized Lymph Node Transplant Planning. Superficial inguinal (groin) vascularized lymph node transplantation is the most common option for the treatment of lymphedema, particularly in combination with free abdominal flap breast reconstruction. This study examines the utility of single-photon emission computed tomographic (SPECT/CT) lymphoscintigraphy for lower extremity reverse lymphatic mapping in presurgical planning for groin vascularized lymph node transplantation and appraises the physiologic lymphatic drainage to the superficial inguinal lymph nodes.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Effects of Appearance-Based Comments and Non-Appearance-Based Evaluations on Body Dissatisfaction and Disordered Eating Urges: An Ecological Momentary Assessment Study. The current study used ecological momentary assessment (EMA) to investigate whether appearance-based comments, social and performance-based evaluations affected levels of body dissatisfaction (BD) and urges to engage in disordered eating behaviors (DE) throughout daily life. A total of 620 participants completed a baseline questionnaire assessing sociodemographic variables. Participants then downloaded a mobile app which alerted them to complete short surveys assessing their levels of BD, DE urges, and experiences of receiving comments and evaluations six times per day for 7 days. Negative appearance-based comments predicted greater levels of state BD, while positive appearance comments predicted lower levels of state BD. Negative social and performance-based evaluations predicted an increase in state BD, while positive evaluations predicted a decrease in this outcome variable. No significant predictor was found for the DE urge outcomes. The present findings suggest that receiving negative and positive feedback in various domains of one's life may predict opposite outcomes for body image. However, these effects do not necessarily associate with urges to engage in DE in a nonclinical population.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Geriatric syndromes and polypharmacy: to prescribe or to proscribe that is the question]. How to apply treatment recommendations from various knowledgeable specialist societies concerning the very complex patient? Within a population weakened by the cumulative effect of comorbidities, loss of autonomy aggravated by geriatric syndromes and biological changes linked to aging which interact with the pharmacokinetics and pharmacodynamics of drugs, there is fertile soil for the advent of adverse conditions linked to simultaneously prescribing multiple treatments. Our aim is to analyze various clinical reasoning tools permitting an appropriate drug prescription while considering the state of health, life expectancy and time to benefit with the aim of reducing iatrogenesis.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Dental Anomalies as Identification Strategies for Unknown Human Remains: Literature Review and Applications. The unique hard and resilient nature of human teeth makes them useful for various forensic odontological examinations. Structural alterations, cultural modifications, pathological variations, and restorative material make them excellent forensic indicators about biological identity of the unknown deceased or living individuals. Variations in the anatomical details of teeth may be imprinted by defective dental development, traumatic damages, pathologies, and nonmasticatory or weaponry use of teeth during an individual's lifetime. Such imprints can be used for comparisons and identification in forensic anthropology. Deliberate dental alterations/modifications and mutilations practiced due to cultural or esthetic purposes have been reported from some contemporary human population groups as well as from some ancient documented skeletal collections. Willful dental modifications have been most commonly done by filling, drilling, grooving, grinding, staining, and chipping. These dental features may be useful only for differentiation of varied anthropological populations, but their forensic utility cannot be ignored, particularly when antemortem dental records are available for comparisons. Various dental developmental anomalies and defects, restorations, pathological signatures, and occupational markers definitely corroborate other methods of forensic identifications, but cannot be used as sole criteria for individualization of unknown human remains retrieved in medicolegal scenarios. This review article attempts to glean information about various characteristic features of teeth and their forensic significance to aid identification of unknown human dental remains found in forensic contexts; its concluding emphasis focuses on the role of such dental individualities in identification strategies for human remains excavated from an abandoned ancient well situated underneath a religious structure at Ajnala (Amritsar), India. The unique dental features, extrinsic staining of anterior teeth, low frequency of dental pathologies, and notched incisors of those excavated remains were suggestive of them belonging to slain sepoy from an historic military regiment.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Decolorization and control of bromate formation in membrane ozonation of humic-rich groundwater. Membrane ozonation of bromide-containing, high-color natural organic matter (NOM) containing groundwater was performed using single-tube polydimethylsiloxane (PDMS) and multi-tube polytetrafluoroethylene (PTFE) membrane contactors, and compared to batch ozonation. For membrane ozonation, dissolved ozone concentration, water color (VIS 436 ), ultraviolet light absorption (UV 254 ) and bromate formation were correlated with ozone dose, ozone gas concentration, hydraulic retention time and Hatta number (Ha). NOM color removal of up to 45 % for the single-tube contactor and 17 % for the multi-tube contactor were achieved while containing bromate formation below 10 µg L -1 . Higher color removal using higher ozone doses was associated with high bromate formation i.e. >>10 µg L -1 . In membrane ozonation, low ozone gas concentrations, long hydraulic retention times and high Ha resulted in low dissolved ozone concentrations due to quenching of ozone by NOM. At specific ozone doses of < 0.5 mg O 3 /mg DOC and Ha > 1, single-tube ozonation resulted in comparable results to batch ozonation while bromate formation was higher in the single-tube contactor at specific ozone doses > 0.5 mg O 3 /mg DOC and Ha < 1. At comparable ozone doses and Ha, bromate formation in the multi-tube contactor was always higher compared to single-tube and batch ozonation. This could be associated with the uneven ozone distribution within the multi-tube contactor. Results show that ozone dose is the major driver for selectivity between bromate formation and NOM color removal in both membrane and batch ozonation. Bromate formation in membrane ozonation may be controlled by adjusting gas concentration, Ha and hydraulic retention time. Membrane module design and process parameters of membrane ozonation reactors significantly affect treatment performance and should be optimized for selective target compound removal over by-product formation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Early and late predictors of postoperative neurocognitive dysfunction in cardiac surgery. Postoperative cognitive dysfunction (POCD) is a multifactorial image characterized by insufficiency in features such as the ability to perform tasks requiring high brain functions. Cognitive dysfunction such as memory loss and decreased concentration, confusion, and delirium are common conditions in some patients in the early period after major surgical interventions such as cardiac surgery. POCD causes delays in postoperative recovery, long return-to-work times, and decreased quality of life. This study aims to demonstrate POCD in early and late stages in patients undergoing cardiac surgery through the Montreal Cognitive Assessment (MoCA) and the Mini Mental Test (MMT). In addition, we aim to determine predictive factors with these neurocognitive tests.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Low-Dose Occupational Exposure to Nickel and Thyroid Hormones. The aim of this study was to evaluate the effects of a low-dose exposure to nickel, as it is present in urban air, on thyroid hormones and on thyrotropin in outdoor workers exposed to urban pollutants.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
The preventive effect of internet-based cognitive behavioral therapy for prevention of depression during pregnancy and in the postpartum period (iPDP): a large scale randomized controlled trial. Prevention of perinatal depression beginning from the antenatal period is essential. Therefore, this study aimed to investigate the effectiveness of recently developed internet-delivered cognitive behavioral therapy (iCBT) for preventing the onset of a major depressive episode (MDE) in the third trimester and at 3 months postpartum.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis]. Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P =0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P =0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P <0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P =0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P <0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P =0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P =0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P =0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Pay close attention to the current characteristics and development trend of severe acute hepatitis with unknown etiology in children worldwide]. In the past, acute hepatitis of unknown etiology in children was sporadic. However, during the last three weeks, there has been a trend of short-term outbreak around the world. As of May 3, 2022, at least 228 cases had been reported in about 20 countries and regions. The main clinical manifestations of the children included abdominal pain, diarrhea, vomiting, jaundice, and hepatomegaly. The liver functions including alanine aminotransferase and total bilirubin increased sharply. About 8.8% of the children needed liver transplantation. The etiology is not clear, but adenovirus type 41 is currently considered to be the most likely cause. Clinicians should keep alert to acute hepatitis of unknown etiology in children, strengthen epidemic surveillance, clinical treatment, and carry out necessary health education.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Magnetic Resonance Imaging of Acute Abdominal Pain in the Pregnant Patient. Evaluation of a pregnant patient presenting with acute abdominal pain can be challenging to accurately diagnose for a variety of reasons, and particularly late in pregnancy. Noncontrast MR remains a safe and accurate diagnostic imaging modality for the pregnant patient presenting with acute abdominal pain, following often an initially inconclusive ultrasound examination, and can be used in most settings to avoid the ionizing radiation exposure of a computed tomography scan. Pathologic processes discussed in this article include some of the more common gastrointestinal, hepatobiliary, genitourinary, and gynecologic causes of abdominal pain occurring in pregnancy, as well as traumatic injuries.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
The Intake of Ultra-Processed Foods and Prevalence of Chronic Kidney Disease: The Health Examinees Study. Emerging evidence links several health outcomes to the consumption of ultra-processed food (UPF), but few studies have investigated the association between UPF intake and kidney function. This cross-sectional study investigated the prevalence of chronic kidney disease (CKD) in relation to UPF intake in Korea. Data were obtained from the 2004-2013 Health Examinees (HEXA) study. The intake of UPF was assessed using a 106-item food frequency questionnaire and evaluated using the NOVA classification. The prevalence of CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/m 2 . Poisson regression models were used to compute the prevalence ratios (PR) of CKD according to quartiles of the proportion of UPF intake (% food weight). A total of 134,544 (66.4% women) with a mean age of 52.0 years and an eGFR of 92.7 mL/min/m 2 were analysed. The median proportion of UPF in the diet was 5.6%. After adjusting for potential confounders, the highest quartile of UPF intake was associated with the highest prevalence of CKD (PR 1.16, 95% CI 1.07-1.25), and every IQR (6.6%) increase in the proportion of UPF in the diet was associated with a 6% higher prevalence of CKD (PR 1.06, 95% CI 1.03-1.09). Furthermore, the highest consumption of UPF was inversely associated with eGFR (Q4 vs. Q1: β -1.07, 95% CI -1.35, -0.79; per IQR increment: (β -0.45, 95% CI -0.58, -0.32). The intake of UPF was associated with a high prevalence of CKD and a reduced eGFR. Longitudinal studies in the Korean population are needed to corroborate existing findings in other populations.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Methylene blue removal using raw and modified biomass Plumeria alba (white frangipani) in batch mode: isotherm, kinetics, and thermodynamic studies. Hazardous dyes used in textile industries are considered high-risk pollutants to the environment. The raw as well as acid-treated Plumeria alba (white frangipani) leaf powder (WFLP and SWFLP) were used for the adsorption of methylene blue (MB) that is available in industrial wastewaters following the batch adsorption technique. The characterizations of adsorbents were done by FTIR, SEM, EDX, TGA, and zeta potential parameters. The adsorption was considered for the effects of temperature, initial dye concentration, solution pH, adsorbent dosage, and contact time. The experimental results obtained in the adsorption of MB were examined by nonlinear error functions like chi-square (χ 2 ), ARE, and MPSD for three isotherm models: Langmuir, Freundlich, and Temkin. The maximum monolayer adsorption capacity, q max (mg/g), was 45.45 mg/g for raw WFLP and 250 mg/g for SWFLP. The adsorbents fitted to the pseudo-second-order kinetic model (R 2 = 0.99) using the experimental data of batch adsorption. The thermodynamic studies explained the spontaneity and nature of adsorption for raw and acid-treated adsorbents. The batch experimental results and characterizations of the adsorbents revealed that the selected adsorbents would be the best adsorbents for the removal of MB from the wastewater solution.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Initial Experience With the NICO Myriad Device for Minimally Invasive Endoscopic Evacuation of Intracerebral Hemorrhage. Intracerebral hemorrhage (ICH) is a devastating form of stroke for which there is no consensus treatment. Although open craniotomy has been explored as a surgical treatment option, multiple minimally invasive (MIS) techniques have been developed including endoscopic evacuation. An adjunctive aspiration device can be used through the working channel to provide an additional degree of freedom and increased functionality regarding clot manipulation and morcellation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mannosylerythritol lipids: production, downstream processing, and potential applications. Mannosylerythritol lipids (MELs) are biosurfactants produced by various fungal species. Depending on the degree of acetylation and further chemical modifications, these glycolipids can show remarkable biological properties, including the increase of water retention in the stratum corneum suppression of melanogenic enzymes tyrosinase-1 and -2, reversion of UV-A radiation-induced aquaporin-3 suppression, skin whitening, and anti-aging effects. These applications of MELs require high purity, which is usually reached by liquid-liquid extraction followed by chromatography, obtaining ≥95% purity. This worked aimed to critically discuss the current state of the art and trends on the production of MELs, including post-production treatment as enzymatic conversion. In addition, their application as skincare or pharmaceutical agents and agricultural biostimulants.	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The cytokinin type-B response regulator PeRR12 is a negative regulator of adventitious rooting and salt tolerance in poplar. Adventitious root (AR) development is an ecologically and economically important biological process that maintains ecological balance, improves plant survivability, and allows for massive vegetative propagation, but its genetic mechanisms are not well understood. Here, eight Arabidopsis response regulator (ARR) genes were cloned and identified in poplar, most of which were detected in the AR, phloem, and xylem and showed remarkable induction at different time points during AR development. Subcellular localization indicated that most of these PeRR genes are in the nucleus. Based on qRT-PCR expression analysis of some genes related to AR development, we inferred that overexpression of PeRR12 (OE_PeRR12) may inhibited AR formation by suppressing the transcription of PeWOX11, PeWOX5, PePIN1 and PePIN3 in poplar while promoting type-A RR transcripts. Correspondingly, exogenous auxin partially restored the rooting of OE_PeRR12 poplar by inhibiting PeRR12 expression. Moreover, the activities of the antioxidant systems of OE_PeRR12 poplars were lower than those of wild-type poplars under salt stress conditions, indicating that PeRR12 may acts as a repressor that mediates salt tolerance by suppressing the expression of PeHKT1;1. Altogether, these results suggest that PeRR12 plays essential roles in mediating AR formation and salinity tolerance in poplar.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Demonstration of mucus simulant clearance in a Bench-Model using acoustic Field-Integrated Intrapulmonary Percussive ventilation. Intrapulmonary Percussive Ventilation (IPV) is a high-frequency airway clearance technique used to help in mucus transport for mechanically ventilated and unventilated patients. Despite the many years of usage, this technique does not provide clear evidence of its intended efficacy. This is mainly attributable to the lack of in vitro observations that show "mucokinesis" towards the direction of the mouth. In the current manuscript, we demonstrate and subsequently propose a mechanism that details the movement of a mucus simulant in the proximal (towards the mouthpiece) direction. Towards this end, a novel method utilizing a high-frequency acoustic field in addition to the conventional air pulsations brought forth by traditional IPV is proposed. Under these conditions, at certain parameter settings, it is shown that the simulant is broken down into much smaller parts and subsequently pushed in the upstream direction gradually over a period of half-hour.	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sclerostin ablation prevents aortic valve stenosis in mice. The objective of this study was to test the hypothesis that targeting sclerostin would accelerate the progression of aortic valve stenosis. Sclerostin (mouse gene, Sost ) is a secreted glycoprotein that acts as a potent regulator of bone remodeling. Antibody therapy targeting sclerostin is approved for osteoporosis but results from a stage III clinical trial showed multiple off-target cardiovascular effects. Wild-type (WT, Sost +/+ ) and Sost -gene knockout-expression (Null, Sost -/- ) mice were generated and maintained to 12 mo of age on a high-cholesterol diet to induce aortic valve stenosis. Mice were examined by echocardiography, histology, and RNAseq. Immortalized valve interstitial cells were developed from each genotype for in vitro studies. Null mice developed a bone overgrowth phenotype, similar to patients with sclerosteosis. Surprisingly, however, WT mice developed hemodynamic signs of aortic valve stenosis, whereas Null mice were unchanged. WT mice had thicker aortic valve leaflets and higher amounts of α-smooth muscle actin, a marker myofibroblast activation and dystrophic calcification, with very little evidence of Runx2 expression, a marker of osteogenic calcification. RNAseq analysis of aortic roots indicated the HOX family of transcription factors was significantly upregulated in Null mice, and valve interstitial cells from Null animals were enriched with Hoxa1, Hoxb2, and Hoxd3 subtypes with downregulated Hoxa7. In addition, Null valve interstitial cells were shown to be less contractile than their WT counterparts. Contrary to our hypothesis, sclerostin targeting prevented hallmarks of aortic valve stenosis and indicates that targeted antibody treatments for osteoporosis may be beneficial for these patients regarding aortic stenosis. NEW & NOTEWORTHY We have found that genetic ablation of the Sost gene (protein: sclerostin) prevents aortic valve stenosis in aged, Western diet mice. This is a new role for sclerostin in the cardiovascular system. To the knowledge of the authors, this is one of the first studies directly manipulating sclerostin in a cardiovascular disease model and the first to specifically study the aortic valve. We also provide a potential new role for Hox genes in cardiovascular disease, noting pan- Hox upregulation in the aortic roots of sclerostin genetic knockouts. The role of Hox genes in postnatal cardiovascular health and disease is another burgeoning field of study to which this article contributes.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Timing and duration of stopovers affects propensity to breed, incubation periods, and nest success of different wintering cohorts of red knots in the Canadian Arctic during the Years 2009 to 2016. Recent interest in migratory connectivity of shorebirds leads to examining the role stopovers and connectivity play in reproductive success. Since many shorebird species are declining, there is a need to determine factors affecting reproductive success. We used light records from 104 geolocators recovered from red knots (Calidris canutus rufa) to examine-incubation success as a function of temporal patterns at stopovers, year (2009-2016), and wintering cohort. Geolocators were attached on leg flags, mainly in Delaware Bay (New Jersey) and Texas. Successful incubation in different years ranged from 21 to 76%; from 8 to 43% of knots did not attempt incubation on breeding grounds. This is the first estimate of the number of shorebirds going to the Arctic that did not breed, since all other estimates of success were derived from field studies based on birds that initiated nests. High breeding success (76%) occurred in only one year (2011). Nearly all of knots stopped in Hudson Bay region. Arrival date and time in the Pre-Arctic, arrival on breeding grounds, year, and wintering cohort were associated with successful incubation. The percentage attempting incubation, and the percentage that were successful, varied by wintering cohort. When only the east coast rufa knots are considered, time spent on Delaware Bay showed a significant duration difference. Knots wintering in Texas had the highest propensity to initiate incubation (96%), and the highest incubation success (67%). Of rufa knots using the Atlantic flyway, those wintering in southern South America had the lowest incubation success rate (25%). We discuss the importance of quality of flyways, opportunities for refuelling during migration, and importance of time at stopovers. These data can be used to understand migratory connectivity, distinguish factors affecting reproductive success of long-distance migrants, determine which parts of the annual cycle require protection, and aid in recovery plans for long-distance migrants.	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cell wall synthesis and remodelling dynamics determine division site architecture and cell shape in Escherichia coli. The bacterial division apparatus catalyses the synthesis and remodelling of septal peptidoglycan (sPG) to build the cell wall layer that fortifies the daughter cell poles. Understanding of this essential process has been limited by the lack of native three-dimensional views of developing septa. Here, we apply state-of-the-art cryogenic electron tomography (cryo-ET) and fluorescence microscopy to visualize the division site architecture and sPG biogenesis dynamics of the Gram-negative bacterium Escherichia coli. We identify a wedge-like sPG structure that fortifies the ingrowing septum. Experiments with strains defective in sPG biogenesis revealed that the septal architecture and mode of division can be modified to more closely resemble that of other Gram-negative (Caulobacter crescentus) or Gram-positive (Staphylococcus aureus) bacteria, suggesting that a conserved mechanism underlies the formation of different septal morphologies. Finally, analysis of mutants impaired in amidase activation (ΔenvC ΔnlpD) showed that cell wall remodelling affects the placement and stability of the cytokinetic ring. Taken together, our results support a model in which competition between the cell elongation and division machineries determines the shape of cell constrictions and the poles they form. They also highlight how the activity of the division system can be modulated to help generate the diverse array of shapes observed in the bacterial domain.	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Biomarkers of nanomaterials hazard from multi-layer data. There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identify mRNA-based toxicity markers and extensively replicate them in multiple independent datasets. We find that models based on combinations of omics-derived features and material intrinsic properties display significantly improved predictive accuracy as compared to physicochemical properties alone.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A MEG compatible, interactive IR game paradigm for the study of visuomotor reach-to-target movements in young children and clinical populations: The Target-Touch Motor Task. The conventional focus on discrete finger movements (i.e., index finger flexion or button-box key presses) has been an effective method to study neuromotor control using magnetoencephalography (MEG). However, this approach is challenging for young children and not possible for some people with physical disability.	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Variability in Intensive Care Utilization for Intracerebral Hemorrhage in the United States: Retrospective Cohort Study. There are urban-rural geographic health disparities in intracerebral hemorrhage (ICH) outcomes. However, there is limited data regarding the relationship between intensive care (ICU) availability and ICH outcomes. We examined whether ICU availability was a significant contributor to ICH outcomes by US geographic region.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Visualizing RNA polymers produced by hot wet-dry cycling. It is possible that the transition from abiotic systems to life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers and polymers. The aim of the study reported here was to verify this claim and visualize the products prepared from solutions composed of single mononucleotides and 1:1 mixture of two mononucleotides. Therefore, we designed experiments that allowed comparisons of all such mixtures representing six combinations of the four mononucleotides of RNA. We observed irregular stringy patches and crystal strands when wet-dry cycling was performed at room temperature (20 °C). However, when the same solutions were exposed to wet-dry cycles at 80 °C, we observed what appeared to be true polymers. Their thickness was consistent with RNA-like products composed of covalently bonded monomers, while irregular strings and crystal segments of mononucleotides dried or cycled at room temperature were consistent with structures assembled and stabilized by weak hydrogen bonds. In a few instances we observed rings with short polymer attachments. These observations are consistent with previous claims of polymerization during wet-dry cycling. We conclude that RNA-like polymers and rings could have been synthesized non-enzymatically in freshwater hot springs on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Intraoral Styloidectomy Using an Endoscope With Tissue Retractor. The extraoral approach with the risk of facial nerve injury and the visible scar is commonly performed for an elongated styloid process, because intraoral styloidectomy is challenging for the deep and limited surgical field. The authors report minimally invasive intraoral styloidectomy using an endoscope with tissue retractor. A 57-year-old female was referred to our department with a left pharyngeal foreign body sensation and pharyngeal pain after head turning and neck compression. Clinical and radiological diagnosis was an elongated styloid process (Eagle syndrome). Because the styloid process could be palpated intraorally, the patient underwent endoscopically-assisted intraoral styloidectomy without tonsillectomy under general anesthesia as minimally invasive surgery. The styloid process was resected safely with a piezoelectric surgical device under endoscopic guidance. The postoperative course was uneventful without complications.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Accurate measurements of self-diffusion coefficients with benchtop NMR using a QM model-based approach. The measurement of self-diffusion coefficients using pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) spectroscopy is a well-established method. Recently, benchtop NMR spectrometers with gradient coils have also been used, which greatly simplify these measurements. However, a disadvantage of benchtop NMR spectrometers is the lower resolution of the acquired NMR signals compared to high-field NMR spectrometers, which requires sophisticated analysis methods. In this work, we use a recently developed quantum mechanical (QM) model-based approach for the estimation of self-diffusion coefficients from complex benchtop NMR data. With the knowledge of the species present in the mixture, signatures for each species are created and adjusted to the measured NMR signal. With this model-based approach, the self-diffusion coefficients of all species in the mixtures were estimated with a discrepancy of less than 2 % compared to self-diffusion coefficients estimated from high-field NMR data sets of the same mixtures. These results suggest benchtop NMR is a reliable tool for quantitative analysis of self-diffusion coefficients, even in complex mixtures.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. With the introduction of immunotherapy, significant improvement has been made in the treatment of head and neck squamous cell carcinoma (HNSCC). However, only a small subset of patients with HNSCC benefit from immunotherapy. The current biomarker, a programmed cell death protein ligand 1 (PD-L1) expression that is widely used in treatment decision making for advanced HNSCC, has only a moderate predictive value. Additionally, PD-L1-based assay has critical inherent limitations due to its highly dynamic nature and lack of standardization. With the advance in molecular techniques and our understanding of biology, more reliable, reproducible, and practical novel biomarkers are being developed. These include but are not limited to neoantigen/mutation characteristics, immune transcriptomes, tumor-infiltrating immune cell composition, cancer epigenomic, proteomics and metabolic characteristics, and plasma-based and organoid assays.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Roles of estrogens, estrogen-like compounds, and endocrine disruptors in adipocytes. Women are subject to constitutional changes after menopause, which increases conditions and diseases prone to cardiovascular risks such as obesity and diabetes mellitus. Both estrogens and androgens influence the individual's metabolic mechanism, which controls the fat distribution and the hypothalamic organization of the regulatory centers of hunger and satiety. While androgens tend to accumulate fat in the splanchnic and the visceral region with an increase in cardiovascular risk, estrogens generate more subcutaneous and extremity distribution of adipose tissue. The absence of estrogen during menopause seems to be the main factor that gives rise to the greater predisposition of women to suffer cardiovascular alterations. However, the mechanisms by which estrogens regulate the energy condition of people are not recognized. Estrogens have several mechanisms of action, which mainly include the modification of specific receptors that belong to the steroid receptor superfamily. The alpha estrogen receptors (ERα) and the beta receptors (ERβ) have a fundamental role in the metabolic control of the individual, with a very characteristic corporal distribution that exerts an influence on the metabolism of lipids and glucose. Despite the significant amount of knowledge in this field, many of the regulatory mechanisms exerted by estrogens and ER continue to be clarified. This review will discuss the role of estrogens and their receptors on the central regulation of caloric expenditure and the influence they exert on the differentiation and function of adipocytes. Furthermore, chemical substances with a hormonal activity that cause endocrine disruption with affectation on estrogen receptors will be considered. Finally, the different medical therapies for the vasomotor manifestations of menopause and their role in reducing obesity, diabetes, and cardiovascular risk will be analyzed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0
Fall-from-Height Detection Using Deep Learning Based on IMU Sensor Data for Accident Prevention at Construction Sites. Workers at construction sites are prone to fall-from-height (FFH) accidents. The severity of injury can be represented by the acceleration peak value. In the study, a risk prediction against FFH was made using IMU sensor data for accident prevention at construction sites. Fifteen general working movements (NF: non-fall), five low-hazard-fall movements, (LF), and five high-hazard-FFH movements (HF) were performed by twenty male subjects and a dummy. An IMU sensor was attached to the T7 position of the subject to measure the three-axis acceleration and angular velocity. The peak acceleration value, calculated from the IMU data, was 4 g or less in general work movements and 9 g or more in FFHs. Regression analysis was performed by applying various deep learning models, including 1D-CNN, 2D-CNN, LSTM, and Conv-LSTM, to the risk prediction, and then comparing them in terms of their mean absolute error (MAE) and mean squared error (MSE). The FFH risk level was estimated based on the predicted peak acceleration. The Conv-LSTM model trained by MAE showed the smallest error (MAE: 1.36 g), and the classification with the predicted peak acceleration showed the best accuracy (97.6%). This study successfully predicted the FFH risk levels and could be helpful to reduce fatal injuries at construction sites.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort. Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Acid-sensing ion channel 1: potential therapeutic target for tumor. Acidic extracellular pH is a major characteristic of tumor tissue, studies suggest that the local pH value of malignant tumor tissues is between 6.0 and 6.9. Acid-sensing ion channel 1 (ASIC1) is proton-gated cation channel activated by low extracellular pH, recently an increasing number of studies have suggested that ASIC1 is involved in different kinds of tumors, which plays an important role in the occurrence and development of tumors. Therefore, this review will summarize studies involved in ASIC1 on tumors and discuss the effect and mechanism of ASIC1 in numerous related tumors, which will provide new perspectives for tumor therapeutic targets.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0
Long-Term Follow-Up on Morbidity Among Women With a History of Gestational Diabetes Mellitus: A Systematic Review. Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A new chiral stationary phase based on noscapine: Synthesis, enantioseparation, and docking study. Noscapine is an isolated compound from the opium poppy, with distinctive chiral structure and chemistry, interacts with other compounds due to having multiple π-acceptors, hydrogen bond acceptors, and ionic sites. Therefore, it has promising applicability for the enantioselective separation of a wide range of polar, acidic, basic, and neutral compounds. A new noscapine derivative chiral stationary phase (ND-CSP) has been synthesized by consecutive N-demethylation, reduction, and N-propargylation of noscapine followed by attachment of a solid epoxy-functionalized silica bed through the 1,3-dipolar Huisgen cycloaddition. The noscapine derivative-based stationary phase provides a considerable surface coverage, which is greater than some commercial CSPs and can validate better enantioresolution performance. The major advantages inherent to this chiral selector are stability, reproducibility after more than 200 tests, and substantial loading capacity. The characterization by Fourier transform infrared (FTIR) spectroscopy and elemental analysis indicated successful functionalization of the silica surface. Chromatographic method conditions like flow rate and mobile phase composition for enantioseparation of various compounds such as warfarin, propranolol, mandelic acid, and a sulfanilamide derivative were optimized. Comparing the experimental results with docking data revealed a clear correlation between the calculated binding energy of ND-CSP and each enantiomer with the resolution of enantiomer peaks.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic. As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
: Short-term effects of exposure to particulate matter on hospital admissions for asthma and chronic obstructive pulmonary disease. We investigated the effects of particulate matter (PM) factors on hospitalization rates for asthma and chronic obstructive pulmonary disease (COPD). We obtained data on pollutants-PM10, PM2.5-in Seoul, South Korea. We also investigated data for asthma and COPD exacerbation that required hospitalization from 2006 to 2016. We used a time-stratified case-crossover design and generalized additive models with log transformation to assess adjusted risk, and conditional logistic regression was performed to analyze these data. Our study showed that PM10 and PM2.5, on different best lag days, were associated with increased risks of COPD or asthma hospitalization. The odds ratios (ORs) for each per-unit increase in PM10 and PM2.5 were higher in patients with male asthma (PM10: OR, 1.012; 95% confidence interval [CI], 1.008-1.016 and PM2.5: OR, 1.015; 95% CI, 1008-1.023), preschool asthma (PM10: OR, 1.015; 95% CI, 1.006-1.015 and PM2.5: OR, 1.015; 95% CI, 1.009-1.024), male COPD (PM10: OR, 1.012; 95% CI, 1.005-1.019 and PM2.5: OR, 1.013; 95% CI, 1.000-1.026), and senior COPD (PM10: OR, 1.016; 95% CI, 1.008-1.024 and PM2.5: OR, 1.022; 95% CI, 1.007-1.036). Increasing PM levels increased hospitalizations for asthma and COPD. Additionally, the consequences may be different according to age and sex, and PM2.5 may have a more significant effect on airway disease patients than PM10.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Adherence to Mediterranean Diet in Croatia: Lessons Learned Today for a Brighter Tomorrow. Non-communicable diseases (NCD) and lifestyle, particularly diet, have a close relationship. Based on the recent statistics, Croatian men and women lead in European overweight lists, which implies pessimistic prognosis in terms of incidence and prevalence of NCDs in the future. One of the possible solutions to overcome weight problems is turn to traditional balanced and sustainable diets, such as the Mediterranean diet. In this study, we assessed adherence towards Mediterranean diet using a validated questionnaire in an online survey and associated adherence scores with several demographic and anthropometric data. Based on the results of a validated Mediterranean Diet Adherence Screener (N = 3326), we assessed the adherence score to be 7.6 ± 2.5. The score tended to depend on sex, residence, age, education, income, and body mass index (BMI); indeed, women, residents of a coastal part of the country, older volunteers, those possessing a higher education degree, those with higher income, and those with lower BMI were associated with higher scores. As income was one of the significant findings related to higher adherence scores, we developed a dietary plan complying with Mediterranean diet principles that, on average, costed less than the average traditional balanced diet menu. Taken together, this study brought new findings regarding target groups who need to be encouraged to make lifestyle changes, and highlighted the first steps on how to make them.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Intelligent Reconstruction Algorithm-Based Computed Tomography Images for Automatic Detection of Gastric Tumor. The aim of this study was to explore the application of computed tomography (CT) images in the diagnosis of gastric tumor under the intelligent reconstruction algorithm (IRA). 120 patients with gastric cancer were selected and all the patients underwent CT scanning, and CT images were analyzed based on the Feldkamp-Davis-Kress algorithm (FDK algorithm) to evaluate the imaging features of gastric lesions. According to biopsy or surgical pathology, the detection rate of CT images was calculated. The results showed that there were three pathological types of benign tumors (polyps, leiomyomas, and mesenchymomas) and three pathological types of malignant tumors (mesenchymomas, adenomas, and lymphomas). In addition, the detection rates of CT scans were different, reaching 94.2% on different orientations of the stomach, 90.7% of benign tumors, and 90.9% of malignant tumors, so the detection rate of different orientations was relatively high. CT images based on the FDK IRA could realize a high detection rate in diagnosis, accurately locate the lesion, and display the characteristics of the lesion and the metastasis of surrounding tissues; there were significant differences between benign and malignant gastric tumors in CT images, and the detection effect was obvious, which is worthy of clinical application and promotion.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Uncovering the dynamic effects of DEX treatment on lung cancer by integrating bioinformatic inference and multiscale modeling of scRNA-seq and proteomics data. Lung cancer is one of the leading causes of cancer-related death, with a five-year survival rate of 18%. It is a priority for us to understand the underlying mechanisms affecting lung cancer therapeutics' implementation and effectiveness. In this study, we combine the power of Bioinformatics and Systems Biology to comprehensively uncover functional and signaling pathways of drug treatment using bioinformatics inference and multiscale modeling of both scRNA-seq data and proteomics data. Based on a time series of lung adenocarcinoma derived A549 cells after DEX treatment, we first identified the differentially expressed genes (DEGs) in those lung cancer cells. Through the interrogation of regulatory network of those DEGs, we identified key hub genes including TGFβ, MYC, and SMAD3 varied underlie DEX treatment. Further gene set enrichment analysis revealed the TGFβ signaling pathway as the top enriched term. Those genes involved in the TGFβ pathway and their crosstalk with the ERBB pathway presented a strong survival prognosis in clinical lung cancer samples. With the basis of biological validation and literature-based curation, a multiscale model of tumor regulation centered on both TGFβ-induced and ERBB-amplified signaling pathways was developed to characterize the dynamic effects of DEX therapy on lung cancer cells. Our simulation results were well matched to available data of SMAD2, FOXO3, TGFβ1, and TGFβR1 over the time course. Moreover, we provided predictions of different doses to illustrate the trend and therapeutic potential of DEX treatment. The innovative and cross-disciplinary approach can be further applied to other computational studies in tumorigenesis and oncotherapy. We released the approach as a user-friendly tool named BIMM (Bioinformatic Inference and Multiscale Modeling), with all the key features available at https://github.com/chenm19/BIMM.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pazopanib restricts small cell lung cancer proliferation via reactive oxygen species-mediated endoplasmic reticulum stress. Pazopanib is an approved multitarget anticancer agent for soft tissue sarcoma (STS) and renal cell carcinoma (RCC), which is also under clinical investigation for other malignancies, including small cell lung cancer (SCLC). However, the potential anti-SCLC mechanisms of pazopanib remain unclear.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Co-Infection of Oral Candida albicans and Porphyromonas gingivalis Is Associated with Active Periodontitis in Middle-Aged and Older Japanese People. Background and Objectives: Candida albicans can be detected in subgingival sites of patients with periodontitis. However, the association between oral Candida albicans and periodontitis has not been fully elucidated in Japanese adults. The aim of this study is to clarify the relationship between oral Candida albicans infection/co-infection of oral C. albicans and Porphyromonas gingivalis and periodontitis among middle-aged and older Japanese people. Materials and Methods: Eighty-six patients (mean age 70.4 years) who visited the Hiroshima University Hospital from April to September 2021 were investigated in this study. Oral swab samples were collected from the tongue surface. C. albicans and P. gingivalis DNA was detected by real-time PCR using specific DNA primer sets. C. albicans -positive participants were classified into two groups according to the presence or absence of intron insertion of C. albicans DNA by PCR analysis. Results: C. albicans was detected in 22 (25.6%) of the 86 patients. Patients in their 80s recorded a higher C. albicans -positive rate (35.3%) compared with other participants. However, there was no significant association between the C. albicans positivity rate and clinical parameters such as sex, age, systemic disease, denture use, or oral health status. Of the 22 C. albicans -positive participants, 10 participants (45.5%) had C. albicans with intron insertion; 70% of participants who had C. albicans with intron insertion exhibited ≥6 mm probing depth. C. albicans / P. gingivalis co-infection was found in 12 patients (14%). Importantly, binomial logistic regression analysis revealed that C. albicans / P. gingivalis co-infection was significantly associated with ≥6 mm periodontal pockets with bleeding on probing ( p = 0.02). Conclusions: Co-infection of C. albicans and P. gingivalis is involved in active periodontitis in middle-aged and older people.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Efficacy and Safety of Apatinib plus Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cancer: A Phase II Trial. Evidence for neoadjuvant chemotherapy combined with targeted therapy for locally advanced esophageal squamous cancer (ESCC) is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of apatinib combined with taxol and cisplatin (ATP) for locally advanced ESCC. All patients were cT3-4aN0-3 M0 (IIIb-IVa) stage, which were confirmed by histopathology. Apatinib was taken orally (425 mg/d) for two cycles, followed by one cycle of rest. Taxol was administered at 135 mg/m 2 intravenously on day 1, and cisplatin was administered at 20 mg/m 2 intravenously on day 1 to day 3. Radical ESCC resection was performed 4 weeks after ATP. The primary endpoint was pathological response rate (pCR). Secondary endpoints were pathologic response rate (MPR), disease-free survival (DFS), overall survival (OS), R0 resection rate, and safety profile. This trial was registered. We evaluated 41 patients for screening from Oct 2018 to July 2020, of whom 39 were enrolled in the study, with a median age of 65 years (range 49-75 years), and 29 (74.4%) were male. Among the 39 patients, 1 was considered unresectable by the multidisciplinary team due to tumor progression, and 38 patients underwent surgery eventually. The median follow-up was 22 months (range 5-29 months), and the follow-up rate was 100%. The 1-year and 2-year OS was 95% and 95%, and the 1-year and 2-year DFS was 85% and 82%, respectively. Thirty-eight (97.3%) successfully underwent R0 resection. Of the 38 evaluable patients, 9 (23.6%) were pCR, and 15 (39.5%) were MPR. The most common ATP-related AEs were nausea (76.9%), leucopenia (53.8%), neutropenia (51.2%) and vomit (51.2%), anemia (41.0%), and hypertension (25.6%). The most frequent grade 3-4 events included leucopenia (15.3%), neutropenia (15.3%), nausea (12.8%), vomit (12.8%), and hypertension (10.2%). No treatment-related death occurred. Neoadjuvant apatinib combined with taxol and cisplatin for locally advanced ESCC showed favorable activity and manageable safety.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Amyloid β, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer's Disease. The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aβ peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of corn distillers grains with yeast bodies and manipulation of dietary cation and anion difference on production, nutrient digestibility, and gas emissions from manure in lactating cows. In a randomized complete block design, 40 lactating Holstein cows (average 98 d in milk and 41 kg/d of milk yield) were randomly assigned to 1 of 4 diets: (1) containing soybean meal as the major protein supplement (CON diet); (2) CON diet with high-protein dried corn distillers grains at 20% on a dry matter (DM) basis by replacing mainly soybean meal (DG diet); (3) DG diet except that high-protein dried corn distillers grains with yeast bodies (extracted after corn ethanol production) was used (DGY diet); or (4) DG diet supplemented with sodium bicarbonate and potassium carbonate to elevate the dietary cation and anion difference (DCAD; DG-DCAD diet). The DCAD of CON, DG, DGY, and DG-DCAD were 185, 62, 67, and 187 mEq/kg of DM, respectively. The experiment began with a 10-d covariate period and then cows were fed the experimental diets for 5 wk (2-wk diet adaptation and 3-wk data collection periods). Dry matter intake and milk yield were measured daily, and spot urine and fecal samples were collected in the last week of the experiment to measure nutrient digestibility; N, S, and P utilization and excretion; and in vitro NH 3 and H 2 S emissions from manure. All data were analyzed using the MIXED procedure of SAS (random effect: block; fixed effects: diets, repeated week, and interactions). During data collection, DM intake was not different among treatment groups, but milk yield tended to be lower (42.4 vs. 39.9 kg/d) for DG, DGY, and DG-DCAD versus CON, which could have been caused by decreases in organic matter and neutral detergent fiber digestibility. Milk protein yield tended to be lower (1.33 vs. 1.24 kg/d) for DG, DGY, and DG-DCAD versus CON. Milk fat yield was lower (1.26 vs. 1.55 kg/d) for DG and DGY versus CON, but that for DG-DCAD (1.43 kg/d) did not differ from CON. Similarly, energy-corrected milk was lower (38.0 vs. 43.3 kg/d) for cows on DG and DGY versus those on CON, but it did not differ between DG-DCAD (40.7 kg/d) and CON. Urinary and fecal N excretion were greater for DG, DGY, and DG-DCAD compared with CON due to greater dietary crude protein content and N intake. However, NH 3 emissions did not differ across treatments. Intakes of dietary P and S were greater for DG, DGY, and DG-DCAD, resulting in greater excretion of those in manure and greater H 2 S emissions from manure compared with CON. These data suggest that the negative effects of feeding distillers grains on production of lactating cows can be partly explained by a decrease in nutrient digestibility (milk yield) and excessive anion load (milk fat). The milk fat response to DG-DCAD suggests that milk fat depression observed with a diet with high content of distillers grains can be partially alleviated by supplementation of cations. In the current study, we observed no beneficial effects of DG containing yeast bodies.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0