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Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells. Recent studies revealed classes of recurrent DNA double-strand breaks (DSBs) in neural stem/progenitor cells, including transcription-associated, promoter-proximal breaks and recurrent DSB clusters in late-replicating, long neural genes that may give rise to somatic brain mosaicism. The mechanistic factors promoting these different classes of DSBs in neural stem/progenitor cells are not understood. Here, we elucidated the genome-wide landscape of RNA:DNA hybrid structures called "R-loops" in primary neural stem/progenitor cells undergoing aphidicolin-induced, mild replication stress to assess the potential contribution of R-loops to the different, recurrent classes of DNA break "hotspots". We find that R-loops in neural stem/progenitor cells undergoing mild replication stress are present primarily in early-replicating, transcribed regions and in genes with promoter GC skew that are associated with cell lineage-specific processes. Surprisingly, most long, neural genes that form recurrent DSB clusters do not show R-loop formation under conditions of mild replication stress. Our findings are consistent with a role of R-loop-associated processes in promoter-proximal DNA break formation in highly transcribed, early replicating regions but suggest that R-loops do not drive replication stress-induced, recurrent DSB cluster formation in most long, neural genes.
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Impact of RNA degradation on next-generation sequencing transcriptome data. RNA sequencing is an innovative technology to study transcriptomes in both biological and clinical research. However, clinical specimens from patients undergoing surgical operations have a major challenge due to sample degradation. This study replicated the process of RNA degradation by maintaining cells at room temperature to achieve none, slight, middle, and high levels of RNA degradation with decreasing RNA integrity numbers (RIN) of approximately 9.8, 6.7, 4.4, and 2.5, respectively. Next, the differential expression of mRNA and long non-coding RNA (lncRNA) was analyzed in the four degradation groups along with pathway enrichment analysis. The results showed that the similarity of lncRNAs exhibited significant differences even for a slight level of RNA degradation compared with the non-degraded RNA sample. Also, the RNA degradation process was found to be universal, global, and random; the differentially expressed genes increased with an increase in degradation but the pathway enrichment phenomenon was not significantly observed.
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Determinants of Postoperative Abdominal Wound Dehiscence among Patients Operated in a Tertiary Hospital. Abdominal wound dehiscence is one of the dreadful complications for surgeons in their daily activities.The Objective of this study was to identify determinants of abdominal would dehiscence among patients operated at Saint Paul hospital millennium medical college.
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The Detrimental Role of Intraluminal Thrombus Outweighs Protective Advantage in Abdominal Aortic Aneurysm Pathogenesis: The Implications for the Anti-Platelet Therapy. Abdominal aortic aneurysm (AAA) is a common cardiovascular disease resulting in morbidity and mortality in older adults due to rupture. Currently, AAA treatment relies entirely on invasive surgical treatments, including open repair and endovascular, which carry risks for small aneurysms (diameter < 55 mm). There is an increasing need for the development of pharmacological intervention for early AAA. Over the last decade, it has been increasingly recognized that intraluminal thrombus (ILT) is involved in the growth, remodeling, and rupture of AAA. ILT has been described as having both biomechanically protective and biochemically destructive properties. Platelets are the second most abundant cells in blood circulation and play an integral role in the formation, expansion, and proteolytic activity of ILT. However, the role of platelets in the ILT-potentiated AAA progression/rupture remains unclear. Researchers are seeking pharmaceutical treatment strategies (e.g., anti-thrombotic/anti-platelet therapies) to prevent ILT formation or expansion in early AAA. In this review, we mainly focus on the following: (a) the formation/deposition of ILT in the progression of AAA; (b) the dual role of ILT in the progression of AAA (protective or detrimental); (c) the function of platelet activity in ILT formation; (d) the application of anti-platelet drugs in AAA. Herein, we present challenges and future work, which may motivate researchers to better explain the potential role of ILT in the pathogenesis of AAA and develop anti-platelet drugs for early AAA.
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Prior SARS-CoV-2 Infection Is Associated With Coronary Vasomotor Dysfunction as Assessed by Coronary Flow Reserve From Cardiac Positron Emission Tomography. Background Cardiovascular complications from COVID-19 contribute to its high morbidity and mortality. The effect of COVID-19 infection on the coronary vasculature is not known. The objective of this study was to investigate the prevalence of coronary vasomotor dysfunction identified by coronary flow reserve from cardiac positron emission tomography in patients with previous COVID-19 infection. Methods and Results All patients who had polymerase chain reaction-confirmed SARS-CoV-2 infection referred for myocardial stress perfusion positron emission tomography imaging at Brigham and Women's Hospital from April 2020 to July 2021 were compared with a matched control group without prior SARS-CoV-2 infection imaged in the same period. The main outcome was the prevalence of coronary vasomotor dysfunction. Myocardial perfusion and myocardial blood flow reserve were quantified using N13-ammonia positron emission tomography imaging. Thirty-four patients with prior COVID-19 were identified and compared with 103 matched controls. The median time from polymerase chain reaction-confirmed SARS-CoV-2 to cardiac positron emission tomography was 4.6 months (interquartile range,1.2-5.6 months). There were 16 out of 34 (47%) patients previously hospitalized for COVID-19 infection. Baseline cardiac risk factors were common, and 18 (53%) patients in the COVID-19 group had abnormal myocardial perfusion. Myocardial blood flow reserve was abnormal (<2) in 44.0% of the patients with COVID-19 compared with 11.7% of matched controls ( P <0.001). The mean myocardial blood flow reserve was 19.4% lower in patients with COVID-19 compared with control patients (2.00±0.45 versus 2.48±0.47, P <0.001). Conclusions Myocardial blood flow reserve was impaired in patients with prior COVID-19 infection compared with cardiovascular risk factor-matched controls, suggesting a relationship between SARS-CoV-2 infection and coronary vascular health. These data highlight the need to assess long-term consequences of COVID-19 on vascular health in future prospective studies.
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A study on the performance and cost-effectiveness of robots in replacing manual nucleic acid collection method: Experience from the COVID-19 pandemic. The COVID-19 pandemic has led nucleic acid collection and detection became a measure to ensure normal life in China. Considering the huge detection demand, it has emerged that robots replace manual sample collection. However, the cost-effectiveness of nucleic acid collection by robots instead of humans remain unknown.
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Fast and non-destructive discriminating the geographical origin of Hangbaiju by hyperspectral imaging combined with chemometrics. Hangbaiju is highly appreciated flower tea for its health benefits, and its quality and price are affected by geographical origin. Fast and accurate identification of the geographical origin of Hangbaiju is very significant for producers, consumers and market regulators. In this work, hyperspectral imaging combined with chemometrics, was used, for the first time, to explore and implement the geographical origin classification of Hangbaiju. The hyperspectral images in the spectral range of 410-2500 nm for 75 samples of five different origins were collected. As a versatile chemometrics tool, bagging classification tree-radial basis function (BAGCT-RBFN), compared with classification tree (CT), radial basis function network (RBFN), was applied to discriminate Hangbaiju samples from different origins. The results showed that BAGCT-RBFN based on optimal wavelengths yielded superior classification performances to CT and RBFN with full wavelengths. The recognition rates (RR) of the training and prediction sets by BAGCT-RBFN were 96.0 % and 92.0 %, respectively. Hyperspectral imaging combined with chemometric can be considered as a powerful, feasible and convenient tool for the classification of Hangbaiju samples from different origins. It promises to be a potential way for origin discriminant analysis and quality monitor in food fields.
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Povidone-Iodine Fails to Eradicate Chronic Suppurative Otitis Media and Demonstrates Ototoxic Risk in Mice. Commercially available povidone-iodine solution can eliminate biofilms and persister cells rapidly in in vivo achievable concentrations without inducing ototoxicity.
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Electric-Field-Based Guidance for Percutaneous Catheter Vessel Crossing. Percutaneous procedures to divert blood flow from one blood vessel to another can be performed with intravascular catheters but demand a method to align a crossing needle from one vessel to another. Fluoroscopic imaging alone is not adequate, and it is preferable to have a sensor on one catheter that detects the correct alignment of an incoming needle. This can be implemented by generating dipole electric fields from the crossing catheter which are detected by a receiving catheter in the target vessel and, thus, can calculate and display the degree of alignment, permitting the operator to rotate the crossing catheter to guarantee alignment when deploying a crossing needle. Catheters were built using this concept and evaluated in vitro. The results show that accurate alignment is achieved, and a successful crossing can be made. The concept is being further developed for further clinical evaluation.
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A Traumatic Intermuscular Hematoma Mimicking a Soft-tissue Tumor: A Case Report and Literature Review. Certain types of soft-tissue tumors are sometimes combined with bleeding, resulting in difficulty distinguishing them from a mere hematoma when patients with unnoticed soft-tissue tumor sustain trauma.
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Effect of Single Housing on Innate Immune Activation in Immunodeficiency Virus-Infected Pigtail Macaques ( Macaca nemestrina ) as a Model of Psychosocial Stress in Acute HIV Infection. Simian immunodeficiency virus (SIV) infection of macaques recapitulates many aspects of HIV pathogenesis and is similarly affected by both genetic and environmental factors. Psychosocial stress is associated with immune system dysregulation and worse clinical outcomes in people with HIV. This study assessed the impact of single housing, as a model of psychosocial stress, on innate immune responses of pigtailed macaques ( Macaca nemestrina ) during acute SIV infection.
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Simple synthesis of PtRu nanoassemblies as signal amplifiers for electrochemical immunoassay of carbohydrate antigen 19-9. In clinical analysis, carbohydrate antigen 19-9 (CA199) is a gold standard for pancreatic cancer diagnosis. Herein, PtRu nanoassemblies (NAs) were synthesized via a facile one-step solvothermal approach, with the help of octylphenoxypolye thoxyethanol (NP-40) acted as a growth-directing molecule, and triethylene glycol (TEG) worked as a reductant and solvent. During the assembly process of small particles, a large number of voids were formed, which significantly increase the specific surface area of the PtRu NAs exhibiting excellent electrocatalytic performance. Incorporating the PtRu NAs as signal amplifiers for potassium ferrocyanide oxidation into the specific molecular recognition of proteins, a facile signal-enhanced electrochemical (EC) immunosensor was developed. Verified by a series of experiments, the proposed immunosensor presented a wide linear range (10 -4 -70 U mL -1 ) and a low detection limit (3.3 × 10 -5 U mL -1 ), accompanied by good reproducibility, selectivity, and stability, which could be applied in human serum samples for the determination of CA199, and was comparable to commercial electrochemiluminescence (ECL) immunoassay. Feasibility of batch fabrication of PtRu NAs makes nanomaterial-based EC immunoassay promising for the determination of similar cancer markers in future.
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Maternal obesity and acute lymphoblastic leukemia risk in offspring: A summary of trends, epidemiological evidence, and possible biological mechanisms. Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented.
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xImpact : Intelligent Wireless System for Cost-Effective Rapid Condition Assessment of Bridges under Impacts. Bridge strikes by over-height vehicles or ships are critical sudden events. Due to their unpredictable nature, many events go unnoticed or unreported, but they can induce structural failures or hidden damage that accelerates the bridge's long-term degradation. Therefore, always-on monitoring is essential for deployed systems to enhance bridge safety through the reliable detection of such events and the rapid assessment of bridge conditions. Traditional bridge monitoring systems using wired sensors are too expensive for widespread implementation, mainly due to their significant installation cost. In this paper, an intelligent wireless monitoring system is developed as a cost-effective solution. It employs ultralow-power, event-triggered wireless sensor prototypes, which enables on-demand, high-fidelity sensing without missing unpredictable impact events. Furthermore, the proposed system adopts a smart artificial intelligence (AI)-based framework for rapid bridge assessment by utilizing artificial neural networks. Specifically, it can identify the impact location and estimate the peak force and impulse of impacts. The obtained impact information is used to provide early estimation of bridge conditions, allowing the bridge engineers to prioritize resource allocation for the timely inspection of the more severe impacts. The performance of the proposed monitoring system is demonstrated through a full-scale field test. The test results show that the developed system can capture the onset of bridge impacts, provide high-quality synchronized data, and offer a rapid damage assessment of bridges under impact events, achieving the error of around 2 m in impact localization, 1 kN for peak force estimation, and 0.01 kN·s for impulse estimation. Long-term deployment is planned in the future to demonstrate its reliability for real-life impact events.
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Research Progress on Hypoglycemic Mechanisms of Resistant Starch: A Review. In recent years, the prevalence of diabetes is on the rise, globally. Resistant starch (RS) has been known as a kind of promising dietary fiber for the prevention or treatment of diabetes. Therefore, it has become a hot topic to explore the hypoglycemic mechanisms of RS. In this review, the mechanisms have been summarized, according to the relevant studies in the recent 15 years. In general, the blood glucose could be regulated by RS by regulating the intestinal microbiota disorder, resisting digestion, reducing inflammation, regulating the hypoglycemic related enzymes and some other mechanisms. Although the exact mechanisms of the beneficial effects of RS have not been fully verified, it is indicated that RS can be used as a daily dietary intervention to reduce the risk of diabetes in different ways. In addition, further research on hypoglycemic mechanisms of RS impacted by the RS categories, the different experimental animals and various dietary habits of human subjects, have also been discussed in this review.
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ARPC1A is regulated by STAT3 to inhibit ferroptosis and promote prostate cancer progression. The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT-qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.
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Developing a professional competence framework for the master of nursing specialist degree program in China: A modified Delphi study. The urgency of ensuring adequate professional competence in clinical nursing practice is evident. However, there is little formal professional competence framework for the education of master's degree students in nursing specialist programs in China.
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Seven days of ischemic preconditioning augments hypoxic exercise ventilation and muscle oxygenation in recreationally trained males. This investigation sought to assess whether single or repeated bouts of ischemic preconditioning (IPC) could improve oxyhemoglobin saturation ([Formula: see text]) and/or attenuate reductions in muscle tissue saturation index (TSI) during submaximal hypoxic exercise. Fifteen healthy young men completed submaximal graded exercise under four experimental conditions: <i>1</i>) normoxia (NORM), <i>2</i>) hypoxia (HYP) [oxygen fraction of inspired air ([Formula: see text]) = 0.14, ∼3,200 m], <i>3</i>) hypoxia preceded by a single session of IPC (IPC1-HYP), and <i>4</i>) hypoxia preceded by seven sessions of IPC, one a day for 7 consecutive days (IPC7-HYP). IPC7-HYP heightened minute ventilation (V̇e) at 80% HYP peak cycling power output (<i>W</i><sub>peak</sub>) (+10.47 ± 3.35 L·min<sup>-1</sup>, <i>P</i> = 0.006), compared with HYP, as a function of increased breathing frequency. Both IPC1-HYP (+0.17 ± 0.04 L·min<sup>-1</sup>, <i>P</i> &lt; 0.001) and IPC7-HYP (+0.16 ± 0.04 L·min<sup>-1</sup>, <i>P</i> &lt; 0.001) elicited greater oxygen consumption (V̇o<sub>2</sub>) across exercise intensities compared with NORM, whereas V̇o<sub>2</sub> was unchanged with HYP alone. [Formula: see text] was unchanged by either IPC condition at any exercise intensity, yet the reduction of muscle TSI during resting hypoxic exposure was attenuated by IPC7-HYP (+9.9 ± 3.6%, <i>P</i> = 0.040) compared with HYP, likely as a function of reduced local oxygen extraction. Considering all exercise intensities, IPC7-HYP attenuated reductions of TSI with HYP (+6.4 ± 1.8%, <i>P</i> = 0.001). Seven days of IPC heightens ventilation, posing a threat to ventilatory efficiency, during high-intensity submaximal hypoxic exercise and attenuates reductions in hypoxic resting and exercise muscle oxygenation in healthy young men. A single session of IPC may be capable of modulating hypoxic ventilation; however, our present population was unable to demonstrate this with certainty.
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Highly selective and sensitive colorimetric detection for glyphosate based on β-CD@DNA-CuNCs enzyme mimics. A colorimetric assay based on an enzyme-inhibition strategy is promising for the on-site detection of pesticide residues. However, very few works of pesticide detection were reported based on the inhibition toward nanozymes although nanozymes have demonstrated many advantages in sensing various targets. Herein, a facile colorimetric detection for Glyp was developed based on β-CD@DNA-CuNCs enzyme mimics. The β-CD@DNA-CuNCs with high peroxidase-like activity was synthesized using random DNA double strands as template and β-CD as surface ligand. β-CD@DNA-CuNCs could catalyze the H 2 O 2 -3,3',5,5'-tetramethylbenzidine (TMB) system. The oxidation product OxTMB with a blue color and presented a large absorption signal at 652 nm. However, Glyp could destroy the synergic effect between redox doublet (Cu 2+ /Cu + ) on the β-CD@DNA-CuNCs surface, resulting in the inhibition of the peroxidase-like activity. Colorimetric detection for Glyp could be established by detecting the changes of absorption signal at 652 nm. The linear range was 0.02-2 μg/mL and the detection limit was 0.85 ng/mL (3δ/s). The method was applied in measuring Glyp spiked in lake water and various food samples. This method had rapidness, high sensitivity, and selectivity advantages, indicating the high application potential in monitoring Glyp residue in food.
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The MdAux/IAA2 Transcription Repressor Regulates Cell and Fruit Size in Apple Fruit. Auxin plays an important role in regulating plant development, and Auxin/indole acetic acid ( Aux/IAA ) is a type of auxin-responsive gene and plays an important role in auxin signaling; to date, although 29 Aux/IAA proteins have been reported in Abrabidopsis thaliana , only parts of the Aux/IAA family gene functions have been identified. We previously reported that a bud sport of 'Longfeng' (LF) apple ( Malus domestica ), named 'Grand longfeng' (GLF), which showed a larger fruit size than LF, has lower expression of MdAux/IAA2 . In this study, we identified the function of the MdAux/IAA2 gene in apple fruit size difference using Agrobacterium -mediated genetic transformation. Overexpression of MdAux/IAA2 decreased the apple flesh callus increment and caused a smaller globular cell size. In addition, overexpression of MdAux/IAA2 in GLF fruit resulted in the reduction of apple fruit size, weight, and cell size, while silencing MdAux/IAA2 in LF apple fruit resulted in an increase in apple fruit weight and cell size. We suggest that the high auxin content depressed the expression of MdAux/IAA2 , and that the downregulated expression of MdAux/IAA2 led to the formation of GLF. Our study suggests a mechanism for fruit size regulation in plants and we will explore the transcription factors functioning in this process in the future.
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Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells. Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation.
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Comparison of thicknesses of talar cartilage, tibialis anterior, and gastrocnemius muscles between high-activity patients with unilateral traumatic transtibial amputation and nonamputated individuals: A clinical and sonographic study. The aim of this study was to compare the thicknesses of intact talar cartilage, tibialis anterior (TA), gastrocnemius medialis (GCM), and gastrocnemius lateralis (GCL) muscles of traumatic unilateral transtibial amputees with that of nonamputated individuals by ultrasound and to investigate the relationship between cartilage and muscle thickness measurements with clinical parameters.
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Shoulder-Touch test to reveal incongruencies in persons with functional motor disorders. Clinical experience suggests that many patients with functional motor disorders (FMD), despite reporting severe balance problems, typically do not fall frequently. This discrepancy may hint towards a functional component. Here, we explored the role of the Shoulder-Touch test, which features a light touch on the patient's shoulders, to reveal a possible functional etiology of postural instability.
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Data-driven monitoring in patients on left ventricular assist device support. Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.
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Neuroprotective effects of Lasmiditan and Sumatriptan in an experimental model of post-stroke seizure in mice: Higher effects with concurrent opioid receptors or K ATP channels inhibitors. Early post-stroke seizure frequently occurs in stroke survivors within the first few days and is associated with poor functional outcomes. Therefore, efficient treatments of such complications with less adverse effects are pivotal. In this study, we investigated the possible beneficial effects of lasmiditan and sumatriptan against post-stroke seizures in mice and explored underlying mechanisms in their effects.
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Platelet function testing using the Multiplate analyzer after administration of aspirin in Aachen minipigs. Knowledge of platelet function in pigs and the effectiveness of antiplatelet therapy is important to ensure proper transferability from animal studies to humans. Our aim was to (1) characterize baseline platelet function of Aachen minipigs using the bedside Multiplate analyzer, (2) compare baseline platelet function with Göttingen minipigs, and (3) characterize platelet inhibition within the first 5 minutes after intravenous administration of acetylsalicylic acid (ASA). We characterized the baseline platelet function and hematological parameters in 9 Aachen minipigs. Historical data of 8 unmedicated Göttingen minipigs were used for comparison of baseline values. Platelet inhibition in Aachen minipigs was tested 1-5 minutes after intravenous administration of 500 mg ASA. Multiplate examinations included the following tests: ASPI test (to assess the effect of ASA), adenosine-diphosphate-test (ADP test) and thrombin receptor activating peptide test (TRAP test). Median values and interquartile range (IQR) of the Multiplate baseline tests in Aachen minipigs were as follows: ASPI: 39 U (IQR = 21-71), ADP: 70 U (IQR = 48-73), and TRAP: 8 U (IQR = 6-9), whereas the values in Göttingen minipigs were as follows: ASPI: 70.5 U (IQR = 60-78), ADP: 51 U (IQR = 45-66), and TRAP: 6.5 U (IQR = 4-8). ASPI values of Göttingen minipigs were significantly higher than those of Aachen minipigs (p = 0.046). Intravenous administration of ASA in Aachen minipigs resulted in significant platelet inhibition after 1 minute, which remained stable over a period of 5 minutes (p≤0.038). Aachen minipigs appeared to have a high variance in arachidonic acid-mediated platelet aggregation. In Aachen minipigs, intravenous ASA administration resulted in immediate platelet inhibition.
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Recurrent Iliopsoas Abscesses Due to Migrated Appendicular Fecalith: A Case Report and Review of the Literature. Appendicular fecaliths have been reported to migrate to nearby organs before or during surgical treatment and become a late source of infection. We report an extremely rare case of recurrent iliopsoas abscesses caused by appendicular fecaliths that have migrated to the psoas muscle before or during the previous appendicectomy for acute appendicitis. In this case, surgical removal of fecaliths cured the iliopsoas abscess.
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Knowledge transfer of eLearning objects: Lessons learned from an intercontinental capacity building project. Effective knowledge transfer of eLearning objects can hasten the adoption and dissemination of technology in teaching and learning. However, challenges exist which hinder inter-organisational knowledge transfer, particularly across continents. The ACoRD project aimed to transfer knowledge on digital learning development from UK/EU (provider) to Malaysian (receiver) higher education institutions (HEIs). This study explores the challenges encountered during the knowledge transfer process and lessons learned.
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A comprehensive study of alternative splicing in malignant pleural mesothelioma identifies potential therapeutic targets in a new cluster with poor survival. Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM.
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Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome. Breathing disturbances are often a primary clinical concern especially during wakefulness of the classic form of Rett syndrome, but data for atypical forms are lacking.
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Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice. Impairment in neurogenesis correlates with memory and  cognitive dysfunction in AD patients. In the recent decade, therapies with stem cell bases are growing and proved to be efficient. This study is a preliminary attempt to explore the impact of NTF-SCs on hippocampal neurogenesis mediated by the Wnt/β-catenin signaling cascade in AD-like mouse brain parenchyma.
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From concepts to treatment: a dialog between a preclinical researcher and a clinician in addiction medicine. The debate surrounding the brain disease model and the associated questioning of the relevance of animal models is polarizing the field of addiction, and tends to widen the gap between preclinical research and addiction medicine. Here, we aimed at bridging this gap by establishing a dialog between a preclinical researcher and a clinician in addiction medicine. Our objective was to evaluate animal models and the neuroscientific conceptualization of addiction in light of alcohol or drug dependence and treatment in patients struggling with an addiction. We sought to determine how preclinical research influenced addiction medicine over past decades, and reciprocally, what can preclinical researchers learn from addiction medicine that could lead to more effective approaches. In this dialog, we talk about the co-evolution of addiction concepts and treatments from neuroscientific and medical perspectives. This dialog illustrates the reciprocal influences and mutual enrichment between the two disciplines and reveals that, although preclinical research might not produce new pharmacotherapies, it does shape the theoretical conceptualization of addiction and could thereby contribute to the implementation of therapeutic approaches.
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Clinical Features, Antimicrobial Resistance, and Serogroups of Nontyphoidal Salmonella Isolated From Infants Less Than 3 Months Old in the Recent Decade. Antibiotic treatment is indicated for infants with nontyphoidal Salmonella (NTS) enterocolitis. However, whether antimicrobial resistance (AMR) is a problem among young infants is unknown. This study investigated the characteristics of NTS infections in young infants.
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Management of Necrotizing Pancreatitis. Necrotizing pancreatitis affects 10% to 15% of all patients with acute pancreatitis. Despite improved understanding of this complex disease, it is still attended by up to 15% mortality. Necrotizing pancreatitis provides the clinical challenges of working in a multi-disciplinary group, determining proper timing for intervention, and identifying appropriate intervention approaches. The step-up approach consists of supportive care initially. When there is documented infected necrosis, treatment begins with antibiotics, progressing to minimally invasive mechanical necrosis intervention, and reserving surgery as the final treatment modality. However, treatment must be tailored to the individual patient. This article provides an overview of necrotizing pancreatitis.
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Predation of ant species Lasius alienus on tick eggs: impacts of egg wax coating and tick species. Several animal species, including ants, have been reported to be capable of predation on ticks. However, determining factors in most interactions between ticks and predators have not yet been fully deciphered. We hypothesized that the ant species Lasius alienus, which is unknown whether it has any impact on ticks, may exhibit predation on the eggs of tick species Hyalomma marginatum, H. excavatum, and Rhipicephalus bursa, and that the tick egg wax can be the main determinant in possible predation. In the study, 6300 tick eggs with the natural wax coating (waxed/untreated) and 2700 dewaxed tick eggs, the wax of which was removed in the laboratory, were repeatedly presented to the foraging workers belonging to three different ant nests in their natural habitat. Depending on the tick species and trials, the rate of the eggs carried by the ants ranged from 12.8 to 52.1% in the waxed and from 59.8 to 78.4% in the dewaxed eggs. It was observed that the dewaxing process both increased the interest of the ants in the eggs and resulted in a reduction in the variation associated with tick species. This study showed that L. alienus has a predatory effect on tick eggs, the severity of this impact is closely associated with the tick species, the tick-associated difference is caused by the species-specific property of the egg wax, and the variety in the protective effects of the wax seems to be an evolutional result of the biological and ecological adaptation process of the species.
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Decreased level of soluble receptor activator of nuclear factor-κβ ligand (sRANKL) in overweight and obese children. Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway - receptor activator of nuclear factor-κβ ligand (RANKL), its receptor RANK and osteoprotegerin (OPG) - takes part not only in bone metabolism but is also involved in the atherosclerosis process. RANKL stimulates osteogenic differentiation and calcification of vascular smooth cells. The associations between the OPG-sRANKL system and various cardiovascular risk factors were displayed. We aimed to evaluate the relationships between serum sRANKL (soluble RANKL) levels and the OPG/sRANKL ratio with cardiometabolic risk factors in overweight and obese children.
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Uni- and multivariate bias adjustment methods in Nordic catchments: Complexity and performance in a changing climate. For climate-change impact studies at the catchment scale, meteorological variables are typically extracted from ensemble simulations provided by global and regional climate models, which are then downscaled and bias-adjusted for each study site. For bias adjustment, different statistical methods that re-scale climate model outputs have been suggested in the scientific literature. They range from simple univariate methods that adjust each meteorological variable individually, to more complex and more demanding multivariate methods that take existing relationships between meteorological variables into consideration. Over the past decade, several attempts have been made to evaluate such methods in various regions. There is, however, still no guidance for choosing appropriate bias adjustment methods for a study at hand. In particular, the question whether the benefits of potentially improved adjustments outweigh the cost of increased complexity, remains unanswered. This paper presents a comprehensive evaluation of the performance of two commonly used univariate and two multivariate bias adjustment methods in reproducing numerous univariate, multivariate and temporal features of precipitation and temperature series in different catchments in Sweden. The paper culminates in a discussion on trade-offs between the potential benefits (i.e., skills and added value) and disadvantages (complexity and computational demand) of each method to offer plausible, defensible and actionable insights from the standpoint of climate-change impact studies in high latitudes. We concluded that all selected bias adjustment methods generally improved the raw climate model simulations, but that not a single method consistently outperformed the other methods. There were, however, differences in the methods' performance for particular statistical features, indicating that other practical aspects such as computational time and heavy theoretical requirements should also be taken into consideration when choosing an appropriate bias adjustment method.
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Knowledge, Attitude and Practices Toward Coronavirus Disease (COVID- 19) in Southeast and South Asia: A Mixed Study Design Approach. Coronavirus has spread to almost every country since its emergence in Wuhan, China and countries have been adopted an array of measures to control the rapid spread of the epidemic. Here, we aimed to assess the person's knowledge, attitude and practices (KAP) toward the COVID-19 epidemic in Southeast and South Asia applying the mixed study design (cross-sectional and systematic review).
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Systematic investigation of the prognostic impact of clonal status of somatic mutations across multiple cancer types. Tumors are genetically heterogeneous and many mutations are actually present in subclonal populations. The clonal status of mutations is valuable for accurate prognosis, clinical management. The aim of this study was to identify the clonal status of somatic mutations and systematically evaluate their prognostic values across various cancer types. We totally identified 227 clonal and 432 subclonal mutations contributed to prognosis and demonstrated the importance of clonal status in improving mutation-related clinical guidance. We further developed a customized multi-step approach to identify gene-specific prognostic patterns of clonal status at pan-cancer level and found some cancer-specific prognostic patterns. The 'subclonal-dependent risk' subpattern was one of the most common subpatterns, it usually accompanied by high genomic in-stability and high extent of intra-tumor heterogeneity and could be used to improve the accuracy of prognostic analysis. Our results revealed the importance of clonal status, especially subclonal mutation in clinical survival.
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Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis. People with HIV (PWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of clonal hematopoiesis and its association with chronic inflammation and CVD in PWH.
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Introduction to the Special Focus: The Affective Neuroscience of Poverty. Growing up in poverty is associated with a heightened risk for mental and physical health problems across the life span, and there is a growing recognition of the role that social determinants of health play in driving these outcomes and inequities. How do the social conditions of poverty get under the skin to influence biology, and through what mechanisms do the stressors of poverty generate risk for a broad range of health problems? The growing field examining the neuroscience of socioeconomic status (SES) proposes that the brain is an entry point or pathway through which poverty and adversity become embedded in biology to generate these disparities. To date, however, the majority of research on the neuroscience of SES has focused on cognitive or executive control processes. However, the relationship between SES and brain systems involved in affective or emotional processes may be especially important for understanding social determinants of health. Accordingly, this Special Focus on The Affective Neuroscience of Poverty invited contributions from authors examining the relationship between SES and brain systems involved in generating and regulating emotions. In this editorial introduction, we (a) provide an overview of the neuroscience of SES; (b) introduce each of the articles in this Special Focus; and (c) discuss the scientific, treatment, and policy implications of studying the affective neuroscience of poverty.
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Construction of a mutant Bacillus subtilis strain for high purity poly-γ-glutamic acid production. To construct a Bacillus subtilis strain for improved purity of poly-γ-glutamic acid.
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Solving the Location Selection Problem of Self-Service Stores from the Perspectives of Sustainability and Uncertainty. This paper presents an improved method for selecting a specific location in the development of convenience stores in municipal areas. This method solves the problem of self-service store location from the perspective of sustainability and uncertainty and adequately considers the characteristics of individual locations with the proposition of an improved grey wolf optimization algorithm. The example presented shows that the improved algorithm has obvious advantages in facilitating the selection of convenience stores with respect to the search precision, stability, and convergence. Based on the macroenvironment, income, and cost, this work establishes a relatively complex, complete, and targeted mathematical model. Finally, taking the Xiaonanzhuang area of Suzhou Street in Beijing as an example, the scientificity, feasibility, and sustainability of the location model are verified.
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Comparative transcriptome analysis of resistant and susceptible Kentucky bluegrass varieties in response to powdery mildew infection. Poa pratensis is one of the most common cold-season turfgrasses used for urban turf building, and it is also widely used in ecological environment management worldwide. Powdery mildew is a common disease of P. pratensis. To scientifically and ecologically control lawn powdery mildew, the molecular mechanism underlying the response of P. pratensis to powdery mildew infection must better understood.
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Fe 2 O 3 -modified graphene oxide mitigates nanoplastic toxicity via regulating gas exchange, photosynthesis, and antioxidant system in Triticum aestivum. The ever-increasing plastic pollution in soil and water resources raises concerns about its effects on terrestrial plants and agroecosystems. Although there are many reports about the contamination with nanoplastics on plants, the presence of magneto-assisted nanomaterials enabling the removal of their adverse impacts still remains unclear. Therefore, the purpose of the current study is to evaluate the potential of nanomaterial Fe 2 O 3 -modified graphene oxide (FGO, 50-250 mg L -1 ) to eliminate the adverse effects of nanoplastics in plants. Wheat plants exposed to polystyrene nanoplastics concentrations (PS, 10, 50 and 100 mg L -1 ) showed decreased growth, water content and loss of photosynthetic efficiency. PS toxicity negatively altered gas exchange, antenna structure and electron transport in photosystems. Although the antioxidant system was partially activated (only superoxide dismutase (SOD), NADPH oxidase (NOX) and glutathione reductase (GR)) in plants treated with PS, it failed to prevent PS-triggered oxidative damage, as showing lipid peroxidation and hydrogen peroxide (H 2 O 2 ) levels. FGOs eliminated the adverse impacts of PS pollution on growth, water status, gas exchange and oxidative stress markers. In addition, FGOs preserve the biochemical reactions of photosynthesis by actively increasing chlorophyll fluorescence parameters in the stressed-wheat leaves. The activities of all enzymatic antioxidants increased, and the H 2 O 2 and TBARS contents decreased. GSH-mediated detoxifying antioxidants such as glutathione S-transferase (GST) and glutathione peroxidase (GPX) were stimulated by FGOs against PS pollution. FGOs also triggered the enzymes and non-enzymes related to the Asada-Halliwell cycle and protected the regeneration of ascorbate (AsA) and glutathione (GSH). Our findings indicated that FGO had the potential to mitigate nanoplastic-induced damage in wheat by regulating water relations, protecting photosynthesis reactions and providing efficient ROS scavenging with high antioxidant capacity. This is the first report on removing PS-induced damage by FGO applications in wheat leaves.
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Photocatalytic Cleavage of C(sp 3 )-N Bond in Trialkylamines to Dialkylamines and Olefins. Development of a new and green strategy for C(sp 3 )-N bond cleavage is very interesting. Herein, photocatalytic cleavage of the C(sp 3 )-N bond of trialkylamines was achieved, with concurrent formation of dialkylamines and olefins. It was found that a rationally designed 2D-Bi 2 WO 6 @1D-LaPO 4 heterostructure was very efficient for the reaction due to its high light collection efficiency and unique catalytic properties. The strategy could be used for different trialkylamines, including triethylamine, tri-n-propylamine, and ethyl-di-isopropylamine. The mechanistic investigation indicated that the catalyst with heterostructure was not only favorable for charge carrier separation but also rendered excited electrons with high reduction capacity. This work opens a way for C(sp 3 )-N bond cleavage of trialkylamines.
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Towards automatic waste containers management in cities via computer vision: containers localization and geo-positioning in city maps. This paper describes the scientific achievements of a collaboration between a research group and the waste management division of a company. While these results might be the basis for several practical or commercial developments, we here focus on a novel scientific contribution: a methodology to automatically generate geo-located waste container maps. It is based on the use of Computer Vision algorithms to detect waste containers and identify their geographic location and dimensions. Algorithms analyze a video sequence and provide an automatic discrimination between images with and without containers. More precisely, two state-of-the-art object detectors based on deep learning techniques have been selected for testing, according to their performance and to their adaptability to an on-board real-time environment: EfficientDet and YOLOv5. Experimental results indicate that the proposed visual model for waste container detection is able to effectively operate with consistent performance disregarding the container type (organic waste, plastic, glass and paper recycling,…) and the city layout, which has been assessed by evaluating it on eleven different Spanish cities that vary in terms of size, climate, urban layout and containers' appearance.
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Trichoderma Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A. The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22's ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T. afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products.
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Efficacy and safety of monoclonal antibody against calcitonin gene-related peptide or its receptor for migraine patients with prior preventive treatment failure: a network meta-analysis. The relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients.
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Synthesis, characterization, and thermal and computational investigations of the L-histidine bis(fluoride) crystal. Nonlinear optical materials have been investigated recently due to their potential technological applications in information storage and communications. In this context, semi-organic crystals can effectively combine the desired nonlinear optical properties of amino acids with the promising mechanical and thermal properties of inorganic materials. In this work, we have synthesized and characterized a semi-organic crystal of the amino acid L-histidine and hydrofluoric acid and investigated the chemical interactions between the organic and inorganic moieties. The crystal of L-histidine bis(fluoride) has been produced by slow solvent evaporation and characterized by X-ray diffraction (XRD) crystallography and thermogravimetric and differential thermal analyses. The XRD conducted using the Rietveld method shows that the unit cell is orthorhombic with the P2 1 2 1 2 space group and contains four L-histidine bis(fluoride) units. Both differential thermal analysis and temperature-dependent XRD show that the crystals are thermally stable up to 191°C and do not undergo phase transition. The computational Hirshfeld surface analysis of the crystal structure reveals the main intermolecular interactions. Density functional theory has been employed to calculate the ionic interaction energy and electrostatic potential maps and confirm the spontaneity of ionic association at 191°C. The combined experimental and computational results show that the thermal stability of the semi-organic L-histidine bis(fluoride) crystal makes it suitable for nonlinear optical applications in optical sensing and communication systems.
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Association between air pollution and CSF sTREM2 in cognitively normal older adults: The CABLE study. Ambient air pollution aggravates the process of Alzheimer's disease (AD) pathology. Currently, the exact inflammatory mechanisms underlying these links from clinical research remain largely unclear.
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Spillover effect of psychological distress from distressed to non-distressed spouse: A cohort study for midlife married couples in Japan. Few studies have evaluated the impact of spousal psychological distress on an individual's distress over time based on detailed measurements of mental status. Hence, we investigate the spillover effect of spousal psychological distress.
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Advances in immunotherapy for glioblastoma multiforme. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor of the central nervous system and has a very poor prognosis. The current standard of care for patients with GBM involves surgical resection, radiotherapy, and chemotherapy. Unfortunately, conventional therapies have not resulted in significant improvements in the survival outcomes of patients with GBM; therefore, the overall mortality rate remains high. Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer and has shown success in different types of aggressive cancers. Recently, healthcare providers have been actively investigating various immunotherapeutic approaches to treat GBM. We reviewed the most promising immunotherapy candidates for glioblastoma that have achieved encouraging results in clinical trials, focusing on immune checkpoint inhibitors, oncolytic viruses, nonreplicating viral vectors, and chimeric antigen receptor (CAR) immunotherapies.
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Optimal Design of Language Teaching Strategy System Based on Smart Video Mode. The accuracy of video and goal enables students to learn and strengthen their ability constantly. Strengthening our country's study initiative degree can promote student study more effectively. As a new teaching method, students can not only obtain the basic knowledge, learning priorities, and difficulties needed for learning through video, but also understand the content of the text, the content of the article, and even cultivate students' interest in many related languages, such as writing, text, sound, image, color, and video, which can be displayed, clarified, and displayed intuitively, creating a free and relaxed learning environment, an interesting background teaching process, encouraging students to experience emotion, including physical experience, and being open and open. Establishing a complete and comprehensive ideological channel to further improve students' acceptance of information is helpful for students' analysis and training, understanding, and evaluation. Therefore, this paper first identifies video and excavates the intrinsic value of video application. This can provide technical and methodological support for the design of video teaching system.
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Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia. Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.
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Factors Related to Omalizumab Drug Survival and Treatment Responses in Chronic Urticaria. This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice.
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Prevalence of Post-Traumatic Stress Disorder (PTSD) in Healthcare Workers following the First SARS-CoV Epidemic of 2003: A Systematic Review and Meta-Analysis. The world is still in the grip of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with putative psychological consequences for healthcare workers (HCWs). Exploring the prevalence of post-traumatic stress disorder (PTSD) during the first SARS-CoV-1 epidemic in 2003 may inform us of the long-term effects of the actual pandemic, as well as putative influencing factors such as contact with the virus, time effects, or the importance of some sociodemographic data. This information may help us develop efficient preventive strategies. Therefore, we conducted a systematic review and meta-analysis on the prevalence of PTSD in HCWs following the SARS-CoV-1 in 2003. PubMed, Embase, Google Scholar, Psychinfo, and Web of Science were searched until September 2022. Random-effects meta-analyses were stratified by the time of follow-up. We included 14 studies: 4842 HCWs (32.0 years old, 84% women). The overall prevalence of PTSD was 14% (95CI 10 to 17%). The prevalence of PTSD was 16% (8 to 24%) during the epidemic, 19% (16 to 22%) within 6 months after the epidemic, and 8% (4 to 13%) more than one year after the end of the epidemic. The longest follow-up was three years after the epidemic, with 10% of HCWs with PTSD. Nevertheless, the prevalence of PTSD was significantly lower more than one year after the end of the epidemic than the first six months after the epidemic (Coefficient -10.4, 95CI -17.6 to -3.2, p = 0.007). In conclusion, the prevalence of PTSD in HCWs was high during the first epidemic of SARS-CoV in 2003 and remained high in the long term. The lessons from the SARS-CoV-1 epidemic may help prevent a wave of PTSD following the latest COVID-19 pandemic.
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Improvements in malaria surveillance through the electronic Integrated Disease Surveillance and Response (eIDSR) system in mainland Tanzania, 2013-2021. Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas.
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Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome. There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2 years of age.
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Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection. SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases.
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Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival. SUMOylation is one of the post-translational modifications that have recently been described as a key regulator of various cellular, nuclear, metabolic, and immunological processes. The process of SUMOylation involves the modification of one or more lysine residues of target proteins by conjugation of a ubiquitin-like, small polypeptide known as SUMO for their degradation, stability, transcriptional regulation, cellular localization, and transport. Herein, for the first time, we report the involvement of the host SUMOylation pathway in the process of infection of Leishmania donovani , a causative agent of visceral leishmaniasis. Our data revealed that infection of L. donovani to the host macrophages leads to upregulation of SUMOylation pathway genes and downregulation of a deSUMOylating gene, SENP1. Further, to confirm the effect of the host SUMOylation on the growth of Leishmania , the genes associated with the SUMOylation pathway were silenced and parasite load was analyzed. The knockdown of the SUMOylation pathway led to a reduction in parasitic load, suggesting the role of the host SUMOylation pathway in the disease progression and parasite survival. Owing to the effect of the SUMOylation pathway in autophagy, we further investigated the status of host autophagy to gain mechanistic insights into how SUMOylation mediates the regulation of growth of L. donovani . Knockdown of genes of host SUMOylation pathway led to the reduction of the expression levels of host autophagy markers while promoting autophagosome-lysosome fusion, suggesting SUMOylation-mediated autophagy in terms of autophagy initiation and autophagy maturation during parasite survival. The levels of reactive oxygen species (ROS) generation, nitric oxide (NO) production, and pro-inflammatory cytokines were also elevated upon the knockdown of genes of the host SUMOylation pathway during L. donovani infection. This indicates the involvement of the SUMOylation pathway in the modulation of protective immune responses and thus favoring parasite survival. Taken together, the results of this study indicate the hijacking of the host SUMOylation pathway by L. donovani toward the suppression of host immune responses and facilitation of host autophagy to potentially facilitate its survival. Targeting of SUMOylation pathway can provide a starting point for the design and development of novel therapeutic interventions to combat leishmaniasis.
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PPSV-23 recommendation and vaccination coverage in China: a cross-sectional survey among healthcare workers, older adults and chronic disease patients. 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is crucial to protecting high-risk groups. This study aimed to investigate the influencing factors of PPSV-23 recommendation among healthcare workers, and PPSV-23 coverage among Chinese older adults and chronic disease patients.
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Integrated electro-coagulation and gravity driven ceramic membrane bioreactor for roofing rainwater purification: Flux improvement and extreme operating case. The collected roofing rainwater with high water quality and large water volume, can alleviate the crisis of water resources and fit the Low-Impact Development (LID) concept. In this work, a novel water purification technology, Electro-Coagulation coupled with Gravity-Driven Ceramic Membrane Bio-Reactor (EC-GDCMBR) was developed for the roofing rainwater purification under long-term operation (136 days). EC-GDCMBR system not only exhibited the better effluent quality, but also obtained the greater flux (~32 LMH). The reason contributed to the high permeability of ceramic membrane and large porosity of biofilm formed by floc growth (~36 μm) during the EC process, which was also proved by SEM image. The coagulation, adsorption, biodegradation, and coprecipitation of EC-GDCMBR was able to synergistically remove the particulate matter, ammonia nitrogen (NH 3 -N), Total Phosphorus (TP), organic substances, and heavy metal (i.e., Cr, Zn, and Cu). In particular, via the analysis of bacterial abundance, Extracellular Polymeric Substances (EPS), Assimilable Organic Carbon (AOC), Adenosine Tri-Phosphate (ATP) and Confocal Laser Scanning Microscopy (CLSM), EC could sweep most free bacteria on the ceramic membrane surface, enhancing the biological purification efficiency. Furthermore, a large amount of Pseudomonas (12.4 %-66.7 %) and Nitrospira (1.46 %-3.16 %) in the aggregates formed the biofilms, improved the NH 3 -N removal. During the long-term operation, there are some unavoidable problems, such as the thick and ripened biofilm of EC-GDCMBR would crack and fall off. Based on this, the current work also studied the reliability of GDCMBR under "extreme operating case", and the results showed that neither the biofilm detachment nor the biofilm breakup had a significant impact on the effluent quality. Overall, the findings of this study suggest the reliability of EC-GDCMBR for the sustainable operation of roofing rainwater purification and improve the application value of decentralized rainwater harvest device.
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Variations in Epidural Steroid Injection Practice Patterns by Pain Medicine Physicians in the United States. Epidural steroid injections (ESI) are one of the most commonly performed pain procedures; however, there has been variation in techniques and approaches amongst pain physicians in the United States. The formation of a multidisciplinary working group was made with considerations to help guide ESI practice.
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A real-world retrospective study of safety, efficacy, compliance and cost of combination treatment with rush immunotherapy plus one dose of pretreatment anti-IgE in Chinese children with respiratory allergies. The efficacy of allergen immunotherapy (AIT) in treating pediatric allergy has been clearly demonstrated, however, many patients hesitate to initiate AIT due to weekly hospital visits during the 3-4 months up-dosing phase. Meanwhile, rush immunotherapy (RIT) shortens the duration of the up-dosing phase to 7 days. However, considering that patients receiving RIT are exposed to the allergens during a much shorter period of time and thus may be at a greater risk of systemic reactions, RIT is currently underused, especially in children. This study investigated the utility of combination treatment with RIT plus 1 dose of pretreatment anti-IgE in children with respiratory allergies.
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Giving Back: The Heart of a Nurse. Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely-and often more personal-perspectives on professional, policy, and clinical issues. Best of the Blog is a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.
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NURF301 contributes to gypsy chromatin insulator-mediated nuclear organization. Chromatin insulators are DNA-protein complexes that can prevent the spread of repressive chromatin and block communication between enhancers and promoters to regulate gene expression. In Drosophila, the gypsy chromatin insulator complex consists of three core proteins: CP190, Su(Hw), and Mod(mdg4)67.2. These factors concentrate at nuclear foci termed insulator bodies, and changes in insulator body localization have been observed in mutants defective for insulator function. Here, we identified NURF301/E(bx), a nucleosome remodeling factor, as a novel regulator of gypsy insulator body localization through a high-throughput RNAi imaging screen. NURF301 promotes gypsy-dependent insulator barrier activity and physically interacts with gypsy insulator proteins. Using ChIP-seq, we found that NURF301 co-localizes with insulator proteins genome-wide, and NURF301 promotes chromatin association of Su(Hw) and CP190 at gypsy insulator binding sites. These effects correlate with NURF301-dependent nucleosome repositioning. At the same time, CP190 and Su(Hw) both facilitate recruitment of NURF301 to chromatin. Finally, Oligopaint FISH combined with immunofluorescence revealed that NURF301 promotes 3D contact between insulator bodies and gypsy insulator DNA binding sites, and NURF301 is required for proper nuclear positioning of gypsy binding sites. Our data provide new insights into how a nucleosome remodeling factor and insulator proteins cooperatively contribute to nuclear organization.
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Does donor conception violate human dignity? The moral acceptability of anonymous gamete donation remains contested. Although the view that the value of parent-child relationships should not depend on genetic ties is "nearly axiomatic" among philosophers and bioethicists, one well-known dissenter remains: David Velleman. I argue that most rebuttals to Velleman have simply talked past him because they have failed to understand his fundamental point-that donor conception is a violation of human dignity and as such is wrong even if it does not harm individuals. I challenge Velleman on his own terms by endorsing his metaphysical picture before showing that donor conception is not necessarily a violation of human dignity. I show this by arguing that gamete donation is held to a double standard of self-knowledge. I develop an account of the self that recognizes that certain kinds of challenges to one's flourishing can contribute to an individual's strength and self-knowledge. I defend my view against objections that genetic knowledge is categorically different from other ways of knowing oneself and I show that donor conception can respect human dignity as long as it meets certain conditions.
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Prognosis of Patients with 1-4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles. This study was designed to evaluate the prognostic implication of gross extrathyroidal extension (ETE) invading the strap muscles after thyroid lobectomy in patients with 1-4 cm papillary thyroid cancer (PTC).
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Immunogenicity, effectiveness, safety and psychological impact of COVID-19 mRNA vaccines. In December 2019, a new single-stranded RNA coronavirus, SARS-CoV-2, appeared in China and quickly spread around the world leading to a pandemic. Infection with SARS-CoV-2 generates symptoms ranging from asymptomatic to severe, occasionally requiring hospitalization in intensive care units, and, in more severe cases, leading to death. Scientists and researchers around the world have made a real race against time to develop various vaccines to slow down and stop the spread of the virus. In addition to conventional viral vector vaccines, new generation mRNA vaccines, BNT152b2 (Comirnaty) and mRNA-1273 (Spikevax), have been developed respectively by Pfizer/BioNTech and Moderna. These vaccines act on immune cells to induce an immune response with the production of specific antibodies against Spike protein of SARS-CoV-2, and to stimulate the differentiation of T and B memory cells. The objective of this review is to provide a detailed picture of the validity of these new vaccines and the safety of vaccination. Not only was the immunogenic effect of mRNA vaccines evaluated, but also the psychosocial impact they had on the population. The data collected show that this type of vaccine can also be an excellent candidate for future treatment and eradication of possible new pathologies with viral and non-viral etiology.
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Effects of risk factors for ovarian cancer in women with and without endometriosis. To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.
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Covalent docking in CDOCKER. Targeted covalent inhibitors (TCIs) are considered to be an important component in the toolbox of drug discovery and about 30% of currently marketed drugs are TCIs. Although these drugs raise concerns about toxicity, their high potencies and prolonged effects result in less-frequent drug dosing and wide therapeutic margins for patients. This leads to increased interests in developing new computational methods to identify novel covalent inhibitors. The implementation of successful in silico docking algorithms have the potential to provide significant savings of time and money in the discovery of lead compounds. In this paper, we describe the implementation and testing of a covalent docking methodology in Rigid CDOCKER and the optimization of the corresponding physics-based scoring function with an additional customizable covalent bond grid potential which represents the free energy change of bond formation between the ligand and the receptor. We optimize the covalent bond grid potential for different common covalent bond formation reaction in TCIs. The average runtime for docking one covalent compound is 15 minutes which is comparable or faster than other well-established covalent docking methods. We demonstrate comparable top rank accuracy compared with other covalent docking algorithms using the pose prediction benchmark dataset for covalent docking algorithms developed by the Keserű group. Finally, we construct a retrospective virtual screening benchmark dataset containing 8 different receptor targets with different covalent bond formation reactions. To our knowledge, this is the largest dataset for benchmarking covalent docking methods. We show that our new covalent docking algorithm has the ability to identify lead compounds among a large chemical space. The largest AUC value is 0.909 for the target receptor CATK and the warhead chemistry of the covalent inhibitors is addition to the aldehyde functionality.
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Perioperative anticoagulation recommendations for cutaneous oncologic surgery: a review of the literature. Consistent perioperative management is important to the practice of dermatologic surgery. With the widespread use of anticoagulant medications, such as aspirin, warfarin, clopidogrel, factor Xa inhibitors, and thrombin inhibitors for a number of cardiovascular indications, it is important to standardize the use of these drugs in the setting of skin cancer surgery. Limited literature is available, however, regarding recommendations for dermatological perioperative anticoagulation management. Most published manuscripts involving anticoagulation and skin cancer surgery focus on complications and outcomes rather than providing guidelines for decision-making. In addition, survey studies have largely shown that even with existing recommendations in the literature, many dermatologists continue to have varying management of these medications. Overall, this review finds compelling evidence to support the safety of continuing anticoagulation therapy, such as warfarin, aspirin, and clopidogrel throughout treatment for cutaneous malignancies. It is important that dermatologists, while having primary care and cardiology available for consultation, are aware of the safety data and feel comfortable managing their patients perioperatively.
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Challenges and opportunities in the application of bioinspired engineered nanomaterials for the recovery of metal ions from mining industry wastewater. Heavy-metal-bearing wastewater is among the most formidable challenges the mining industry currently faces in maintaining its social license to operate. Amongst the technologies available for metal ion adsorption, bioinspired engineering nanomaterials have emerged as one which exhibits great promise. However, current processes used for the preparation of adsorbents (including nanoscale activated carbon and biochar) represent a source of adverse impacts on the environment. In contrast, the application of biogenic-nanoparticles, i.e., those derived from processes catalysed by microbiota, has received significant attention in the last few years. Coupled with this, the use of naturally occurring reagents is of major importance for the sustainability of this emerging industry. This paper analyses the life cycle assessment (LCA) of the synthesis of adsorbents derived from agricultural wastes. Moreover, rather than simply recovering the ecotoxic metals from wastewater, the potential to valorise dissolved metals into high-value metallic nanoparticle products is discussed. LCA analysis revealed that the adsorbent had some adverse impact on the environment. The agricultural wastes contributed 27.86% to global warming, 54.64% to ozone formation, 33.06% to fine particles, and 98.24% to marine eutrophication. Mining wastewater is an important, and largely currently unexploited, source of metal value. However, the often-low concentration of such metals dictates that their conversion into high-value products (such as engineered nanoparticles) is an important new research frontier. Within this the use of biosynthesis methods has emerged as having great potential due to a range of beneficial attributes, including low cost, high efficacy and/or environmental compatibility.
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Omega-3 and cardiovascular prevention - Is this still a choice? There is currently growing attention being paid to the role of elevated triglycerides (TGs) as important mediators of residual atherosclerotic cardiovascular disease (ASCVD) risk. This role is supported by genetic studies and by the persistent residual risk of ASCVD, even after intensive statin therapy. Although TG lowering drugs have shown conflicting results when tested in cardiovascular outcome trials, data from the REDUCE-IT study with the ethyl ester of ω-3 eicosapentaenoic acid (EPA) have revived hope in this area of research. The aim of the present review is to critically discuss the most recent large trials with ω-3 fatty acids (FAs) trying to elucidate mechanistic and trial-related differences, as in the case of REDUCE-IT and STRENGTH studies. The ω-3 FAs may lower cardiovascular risk through a number of pleiotropic mechanisms, e.g., by lowering blood pressure, by mediating antithrombotic effects, by providing precursors for the synthesis of specialized proresolving mediators that can inhibit inflammation or by modulating the lipid rafts enriched in cholesterol and sphingolipids. In conclusion, in a field fraught with uncertainties, the ω-3 FAs and especially high dose icosapent ethyl (the ethyl ester of EPA) are at present a most valuable therapeutic option to reduce the ASCVD risk.
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[Postdural puncture headache in obstetrics : Pathogenesis, diagnostics and treatment]. Postdural puncture headache (PDPH) is one of the most important complications of peripartum neuraxial analgesia. Loss of cerebrospinal fluid volume and pressure as well as compensatory intracranial vasodilation are assumed to be responsible. Potentially severe long-term sequelae necessitate the correct diagnosis of PDPH, exclusion of relevant differential diagnoses (with atypical symptoms and when indicated via imaging techniques) and rapid initiation of effective treatment. Nonopioid analgesics, caffeine and occasionally theophylline, gabapentin and hydrocortisone are the cornerstones of pharmacological treatment, while the timely placement of an autologous epidural blood patch (EBP) represents the gold standard procedure when symptoms persist despite the use of analgesics. Procedures using neural treatment are promising alternatives, especially when an EBP is not desired by the patient or is contraindicated. Interdisciplinary and interprofessional consensus standard procedures can contribute to optimization of the clinical management of this relevant complication.
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New hope for Parkinson's disease treatment: Targeting gut microbiota. There might be more than 10 million confirmed cases of Parkinson's disease (PD) worldwide by 2040. However, the pathogenesis of PD is still unclear. Host health is closely related to gut microbiota, which are affected by factors such as age, diet, and exercise. Recent studies have found that gut microbiota may play key roles in the progression of a wide range of diseases, including PD. Changes in the abundance of gut bacteria, such as Helicobacter pylori, Enterococcus faecalis, and Desulfovibrio, might be involved in PD pathogenesis or interfere with PD therapy. Gut microbiota and the distal brain achieve action on each other through a gut-brain axis composed of the nervous system, endocrine system, and immune system. Here, this review focused on the current understanding of the connection between Parkinson's disease and gut microbiota, to provide potential therapeutic targets for PD.
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Prevent Problematic Missing Data. Over the course of 2022, we have encouraged our community to adopt increasingly effective methods of mitigating the harm missing data poses to a valid science of nursing education. With our last column entry for the year, we conclude our emphasis by looking at a few approaches to the prevention of problematic missingness that can be implemented prior to collecting data. [J Nurs Educ. 2022;61(11):657-658.] .
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Understanding the transmission dynamics of a large-scale measles outbreak in Southern Vietnam. Southern Vietnam experienced a large measles outbreak of over 26,000 cases during 2018-2020. We aimed to understand and quantify the measles spread in space-time dependence and the transmissibility during the outbreak.
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Simulation of Pressure-Driven and Channel-Based Microfluidics on Different Abstract Levels: A Case Study. A microfluidic device, or a Lab-on-a-Chip (LoC), performs lab operations on the microscale through the manipulation of fluids. The design and fabrication of such devices usually is a tedious process, and auxiliary tools, such as simulators, can alleviate the necessary effort for the design process. Simulations of fluids exist in various forms and can be categorized according to how well they represent the underlying physics, into so-called abstraction levels. In this work, we consider simulation approaches in 1D, which are based on analytical solutions of simplified problems, and approaches in 2D and 3D, for which we use two different Computational Fluid Dynamics (CFD) methods-namely, the Finite Volume Method (FVM) and the Lattice-Boltzmann Method (LBM). All these methods come with their pros and cons with respect to accuracy and required compute time, but unfortunately, most designers and researchers are not aware of the trade-off that can be made within the broad spectrum of available simulation approaches for microfluidics and end up choosing a simulation approach arbitrarily. We provide an overview of different simulation approaches as well as a case study of their performance to aid designers and researchers in their choice. To this end, we consider three representative use cases of pressure-driven and channel-based microfluidic devices (namely the non-Newtonian flow in a channel, the mixing of two fluids in a channel, and the behavior of droplets in channels). The considerations and evaluations raise the awareness and provide several insights for what simulation approaches can be utilized today when designing corresponding devices (and for what they cannot be utilized yet).
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Chemical and Synthetic Biology Approaches for Cancer Vaccine Development. Cancer vaccines have been considered promising therapeutic strategies and are often constructed from whole cells, attenuated pathogens, carbohydrates, peptides, nucleic acids, etc. However, the use of whole organisms or pathogens can elicit unwanted immune responses arising from unforeseen reactions to the vaccine components. On the other hand, synthetic vaccines, which contain antigens that are conjugated, often with carrier proteins, can overcome these issues. Therefore, in this review we have highlighted the synthetic approaches and discussed several bioconjugation strategies for developing antigen-based cancer vaccines. In addition, the major synthetic biology approaches that were used to develop genetically modified cancer vaccines and their progress in clinical research are summarized here. Furthermore, to boost the immune responses of any vaccines, the addition of suitable adjuvants and a proper delivery system are essential. Hence, this review also mentions the synthesis of adjuvants and utilization of biomaterial scaffolds, which may facilitate the design of future cancer vaccines.
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Asymmetric Synthesis of Spiro[Azetidine-3,3'-Indoline]-2,2'-Diones via Copper(I)-Catalyzed Kinugasa/C-C Coupling Cascade Reaction. Spiro[azetidine-indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine-indolines] are limited to chiral spiro[azetidine-2,3'-indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine-3,3'-indolines] remains unexplored. In this work, the first copper(I)-catalyzed asymmetric Kinugasa/aryl C-C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine-3,3'-indoline]-2,2'-diones in good yields and with high enantioselectivity.
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Dithiol Based on l-Cysteine and Cysteamine as a Disulfide-Reducing Agent. We report the synthesis, chemical properties, and disulfide bond-reducing performance of a dithiol called NACMEAA, conceived as a hybrid of two biologically relevant thiols: cysteine and cysteamine. NACMEAA is conveniently prepared from inexpensive l-cystine in an efficient manner. As a nonvolatile, highly soluble, and neutral compound at physiological pH with the first thiol p K a value of 8.0, NACMEAA is reactive and user-friendly. We also demonstrate that NACMEAA reduces disulfide bonds in GSSG and lysozyme.
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Enhanced cadmium phytoremediation capacity of poplar is associated with increased biomass and Cd accumulation under nitrogen deposition conditions. Nitrogen (N) deposition plays a significant role in soil cadmium (Cd) phytoremediation, and poplar has been considered for the remediation of contaminated soil because of its enormous biomass and strong Cd resistance. To reveal the underlying physiological and root phenotypic mechanisms of N deposition affecting Cd phytoextraction in poplar, we assessed root phenotypic characteristics, Cd absorption and translocation, chlorophyll fluorescence performance, and antioxidant enzyme activities of a clone of Populus deltoides × P. nigra through combined greenhouse Cd and N experiments. Our results showed that Cd significantly changed the root phenotype by reducing root length, tip number, and diameter. Cd also caused the peroxidation of lipids, damaged the photosystem II (PSII) reaction centre, and reduced photosynthetic capacity, resulting in a decrease in biomass accumulation in poplar. The N60 (60 kg N·ha -1 ·yr -1 ) and N90 (90 kg N·ha -1 ·yr -1 ) treatments promoted the net photosynthetic rate of poplar by increasing the activity of antioxidant enzymes and proline content and repairing the PSII reaction centre, thus increasing the biomass accumulation of poplar exposed to Cd stress. Simultaneously, the N60 and N90 treatments might have increased Cd uptake from the soil by upregulating total root length, root tips, and fine root length. Cd mainly accumulated in roots and stems but not in leaves. The N30 (30 kg N·ha -1 ·yr -1 ) treatment had no obvious effects on these parameters compared with the single Cd treatment. Consequently, our study suggested that adequate N can improve biomass and Cd accumulation to enhance the phytoremediation capacity of poplar for Cd, which might be related to the improvement of leaf physiological defence and the change in root phenotypic characteristics.
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Protocol of an iterative qualitative study to develop a molecular testing decision aid for shared decision-making in patients with lung cancer after surgery. Although molecular testing is crucial for many patients with lung cancer, the decision to carry out molecular testing is not easy to make in actual clinical scenarios. Using a specific decision aid (DA) to conduct shared decision-making (SDM) may help ameliorate this problem. However, no DA currently exists for lung cancer molecular testing (DA_LCMT). We aim to develop an evidence-based, iteratively refined DA, which may facilitate SDM and improve the quality of SDM.
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Parallelization with Dual-Trap Single-Column Configuration Maximizes Throughput of Proteomic Analysis. Proteomic analysis on the scale that captures population and biological heterogeneity over hundreds to thousands of samples requires rapid mass spectrometry methods, which maximize instrument utilization (IU) and proteome coverage while maintaining precise and reproducible quantification. To achieve this, a short liquid chromatography gradient paired to rapid mass spectrometry data acquisition can be used to reproducibly quantify a moderate set of analytes. High-throughput profiling at a limited depth is becoming an increasingly utilized strategy for tackling large sample sets but the time spent on loading the sample, flushing the column(s), and re-equilibrating the system reduces the ratio of meaningful data acquired to total operation time and IU. The dual-trap single-column configuration (DTSC) presented here maximizes IU in rapid analysis (15 min per sample) of blood and cell lysates by parallelizing trap column cleaning and sample loading and desalting with the analysis of the previous sample. We achieved 90% IU in low microflow (9.5 μL/min) analysis of blood while reproducibly quantifying 300-400 proteins and over 6000 precursor ions. The same IU was achieved for cell lysates and over 4000 proteins (3000 at CV below 20%) and 40,000 precursor ions were quantified at a rate of 15 min/sample. Thus, DTSC enables high-throughput epidemiological blood-based biomarker cohort studies and cell-based perturbation screening.
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Synthetic gRNA/Cas9 Ribonucleoprotein Inhibits HIV Reactivation and Replication. The current antiretroviral therapy (ART) for human immunodeficiency virus (HIV) can halt viral replication but cannot eradicate HIV infection because proviral DNA integrated into the host genome remains genetically silent in reservoir cells and is replication-competent upon interruption or cessation of ART. CRISPR/Cas9-based technology is widely used to edit target genes via mutagenesis (i.e., nucleotide insertion/deletion and/or substitution) and thus can inactivate integrated proviral DNA. However, CRISPR/Cas9 delivery systems often require viral vectors, which pose safety concerns for therapeutic applications in humans. In this study, we used synthetic guide RNA (gRNA)/Cas9-ribonucleoprotein (RNP) as a non-viral formulation to develop a novel HIV gene therapy. We designed a series of gRNAs targeting different HIV genes crucial for HIV replication and tested their antiviral efficacy and cellular cytotoxicity in lymphoid and monocytic latent HIV cell lines. Compared with the scramble gRNA control, HIV-gRNA/Cas9 RNP-treated cells exhibited efficient viral suppression with no apparent cytotoxicity, as evidenced by the significant inhibition of latent HIV DNA reactivation and RNA replication. Moreover, HIV-gRNA/Cas9 RNP inhibited p24 antigen expression, suppressed infectious viral particle production, and generated specific DNA cleavages in the targeted HIV genes that are confirmed by DNA sequencing. Because of its rapid DNA cleavage, low off-target effects, low risk of insertional mutagenesis, easy production, and readiness for use in clinical application, this study provides a proof-of-concept that synthetic gRNA/Cas9 RNP drugs can be utilized as a novel therapeutic approach for HIV eradication.
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Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways. Osteosarcoma (OS) is the most prevalent malignant bone tumor with poor prognosis. Developing new drugs for the chemotherapy of OS has been a focal point and a major obstacle of OS treatment. Nitazoxanide (NTZ), a conventional anti-parasitic agent, has got increasingly noticed because of its favorable antitumor potential. Herein, we investigated the effect of NTZ on human OS cells in vitro and in vivo . The results obtained in vitro showed that NTZ inhibited the proliferation, migration and invasion, arrested cell cycle at G1 phase, while induced apoptosis of OS cells. Mechanistically, NTZ suppressed the activity of AKT/mTOR and Wnt/β-catenin signaling pathways of OS cells. Consistent with the results in vitro , orthotopic implantation model of 143B OS cells further confirmed that NTZ inhibited OS cells growth and lung metastasis in vivo . Notably, NTZ caused no apparent damage to normal cells/tissues. In conclusion, NTZ may inhibit tumor growth and metastasis of human OS cells through suppressing AKT/mTOR and Wnt/β-catenin signaling pathways.
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Prevalence and predictors of urine culture contamination in primary care: A cross-sectional study. Antimicrobial resistance is a global health threat. To slow resistance and preserve antibiotics, stewardship interventions are increasingly promoted and mandated. Urine cultures are the most common microbiological test in the outpatient setting. Contamination most likely occurs during urine collection from surrounding vaginal, perineal, and epidermal flora. Sample contamination can lead to incorrect diagnosis, unnecessary or inappropriate treatment, poor patient outcomes, and higher costs. Therefore, ensuring proper collection of urinary samples serves as a prime diagnostic stewardship target, one that international nursing societies increasingly endorse as an opportunity for nurse involvement.
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An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes. Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses.
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GAIN: A Gated Adaptive Feature Interaction Network for Click-Through Rate Prediction. CTR (Click-Through Rate) prediction has attracted more and more attention from academia and industry for its significant contribution to revenue. In the last decade, learning feature interactions have become a mainstream research direction, and dozens of feature interaction-based models have been proposed for the CTR prediction task. The most common approach for existing models is to enumerate all possible feature interactions or to learn higher-order feature interactions by designing complex models. However, a simple enumeration will introduce meaningless and harmful interactions, and a complex model structure will bring a higher complexity. In this work, we propose a lightweight, yet effective model called the Gated Adaptive feature Interaction Network (GAIN). We devise a novel cross module to drop meaningless feature interactions and preserve informative ones. Our cross module consists of multiple gated units, each of which can independently learn an arbitrary-order feature interaction. We combine the cross module with a deep module into GAIN and conduct comparative experiments with state-of-the-art models on two public datasets to verify its validity. Our experimental results show that GAIN can achieve a comparable or even better performance compared to its competitors. Furthermore, in order to verify the effectiveness of the feature interactions learned by GAIN, we transfer learned interactions to other models, such as Logistic Regression (LR) and Factorization Machines (FM), and find out that their performance can be significantly improved.
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Mucoepidermoid carcinoma of the breast: A case report and literature review focused on radiological findings. Mucoepidermoid carcinoma (MEC) of the breast is a rare entity, with an estimated incidence of only 0.2% to 0.3% of all primary breast tumors. The radiological features of breast MEC have scarcely been investigated mainly because of its rarity. In this article, we present a case of breast MEC diagnosed at our hospital and review the literature, focusing on radiological findings and radiologic-pathologic correlations that could improve clinical management of this entity. To the best of our knowledge, our study is the first review of the literature that focuses on the radiological features of breast MEC.
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Land-atmosphere coupling speeds up flash drought onset. Flash drought is a type of drought with rapid onset and great destructiveness, which poses a serious threat to agriculture, ecosystem, and environment without sufficient early warning. The rapid onset is a unique feature that distinguishes flash drought from conventional dry conditions, but its underlying mechanism remains unclear. With the 42-years reanalysis data, we compared the differences in convective triggering potential and atmospheric humidity indices between flash drought onset and conventional dry conditions over China. We found that the dry land-atmospheric coupling can speed up flash drought onset by suppressing precipitation and increasing evapotranspiration. Results show that the increase of sensible heat transport during flash drought onset can intensify the heating of atmosphere, and enhance the lifting condensation level deficit which efficiently inhibits the convective precipitation. Meanwhile, the atmospheric drying significantly increases the evapotranspiration demand and decreases soil moisture, thus speeds up the drought onset. In this regard, the drier land surface makes the atmosphere drier through land-atmosphere coupling, and the rapid drought onset can be maintained via the positive feedback. Although the contribution of precipitation deficit averaged over China is 92 %, the evapotranspiration excess is also critical for increasing the onset speed especially over South China where the flash drought hotspot exists. With the contribution of evapotranspiration increased by about 26 %, the flash drought onset speed over China almost doubled. This study highlights the importance of dry land-atmospheric coupling for speeding up flash drought onset and provides insights for flash drought diagnosis and prediction.
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[Research progress of induced pluripotent stem cells in promoting wound healing of diabetic foot ulcers]. Chronic wounds such as diabetic foot ulcers are epidemic, which bring huge burdens to both the patients and the society. However, with current treatment methods, diabetic foot ulcers often heal poorly and recur frequently, so it is urgent and important to find new and advanced therapies. Stem cell therapy has been proved by a large number of pre-clinical and clinical studies as a potential treatment for chronic wounds. However, the acquisition of stem cells often depends on invasive techniques, and immunogenicity and limited cell survival in vivo also limit the large-scale application and promotion of stem cell therapy. In the recent years, with the development and advance of induced pluripotent stem cell (iPSC) technology, it has shown a strong translational potential in the treatment of chronic wounds such as diabetic foot ulcers. This article reviews the applications and prospect of iPSCs in animal wound healing models including diabetic ulcers and limb ischemia, the limitations of their clinical application, and the methods to improve their safety.
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Sustainable Data-Driven Secured Optimization Using Dynamic Programming for Green Internet of Things. The development of smart applications has benefited greatly from the expansion of wireless technologies. A range of tasks are performed, and end devices are made capable of communicating with one another with the support of artificial intelligence technology. The Internet of Things (IoT) increases the efficiency of communication networks due to its low costs and simple management. However, it has been demonstrated that many systems still need an intelligent strategy for green computing. Establishing reliable connectivity in Green-IoT (G-IoT) networks is another key research challenge. With the integration of edge computing, this study provides a Sustainable Data-driven Secured optimization model (SDS-GIoT) that uses dynamic programming to provide enhanced learning capabilities. First, the proposed approach examines multi-variable functions and delivers graph-based link predictions to locate the optimal nodes for edge networks. Moreover, it identifies a sub-path in multistage to continue data transfer if a route is unavailable due to certain communication circumstances. Second, while applying security, edge computing provides offloading services that lower the amount of processing power needed for low-constraint nodes. Finally, the SDS-GIoT model is verified with various experiments, and the performance results demonstrate its significance for a sustainable environment against existing solutions.
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Dissecting the intracellular pancreatic tumor microbiome at single-cell level. Microorganisms play a role in the progression of various cancers. In this issue of Cancer Cell, Ghaddar et al. traced bacteria in pancreatic tumors at single-cell resolution and associated their intracellular presence with cell-type-specific transcriptional shifts, with links to clinical prognosis.
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National Trends in the Achievement of Recommended Strategies for Stroke Prevention in U.S. Adults With Type 2 Diabetes, 2001-2018. To assess the national prevalence of and trends in achieving current guideline-recommended treatment goals and pharmacotherapies for primary and secondary prevention of stroke among U.S. adults with type 2 diabetes (T2D).
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Emotional salience but not valence impacts anterior cingulate cortex conflict processing. Stimuli that evoke emotions are salient, draw attentional resources, and facilitate situationally appropriate behavior in complex or conflicting environments. However, negative and positive emotions may motivate different response strategies. For example, a threatening stimulus might evoke avoidant behavior, whereas a positive stimulus may prompt approaching behavior. Therefore, emotional stimuli might either elicit differential behavioral responses when a conflict arises or simply mark salience. The present study used functional magnetic resonance imaging to investigate valence-specific emotion effects on attentional control in conflict processing by employing an adapted flanker task with neutral, negative, and positive stimuli. Slower responses were observed for incongruent than congruent trials. Neural activity in the dorsal anterior cingulate cortex was associated with conflict processing regardless of emotional stimulus quality. These findings confirm that both negative and positive emotional stimuli mark salience in both low (congruent) and high (incongruent) conflict scenarios. Regardless of the conflict level, emotional stimuli deployed greater attentional resources in goal directed behavior.
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Advanced unified monophasic lipid extraction protocol with wide coverage on the polarity scale optimized for large-scale untargeted clinical lipidomics analysis of platelets. Lipid extraction is a critical step in sample preparation of lipidomics studies. Biphasic liquid-liquid extraction protocol with methyl tert-butyl ether (MTBE)/methanol (MeOH) as organic solvents are widely adopted by researchers nowadays as an eco-friendly replacement of classic Folch, and Bligh&Dyer protocols. Yet, it has some limitations such as suboptimal performance for the most polar lipids (e.g. acylcarnitines), complicated handling as it requires phase separation, and is therefore non-ideal for large-scale clinical studies. To advance the extraction protocol for large-scale clinical lipidomics, in this study we explored i) 6 different extraction solvent systems, ii) distinct processing procedures (sonication, mechanical cell lysis and bead homogenizer), and iii) also 7 different reconstitution solvents. The extraction systems investigated included biphasic systems MTBE/MeOH/H 2 O and Hexane/2-propanol (IPA)/1 M acetic acid, and monophasic systems MTBE/MeOH/CHCl 3 , IPA/H 2 O (90% IPA), MeOH/MTBE/IPA, and IPA/H 2 O/MTBE as solvent system for lipid extraction of human platelets. Extraction recovery was investigated by repeated extraction cycles. Subcellular extraction efficiency was assessed by the mitochondria-specific cardiolipins. It turned out that monophasic extraction with MeOH/MTBE/IPA (1.3:1:1, v/v/v), bead homogenizer for cell disruption and MeOH/MTBE (1:1, v/v) as reconstitution solvent provide optimal cellular and subcellular extraction efficiencies for both polar (e.g. acylcarnitines) and apolar lipids (e.g. triglycerides). It is simplified (no phase separation), eco-friendly (reduced solvent consumption and no halogenated ones), fast (5 min for 24 samples in parallel), and can be easily adapted for cells, plasma, and tissue. Therefore, it has great potential for large-scale clinical lipidomics studies.
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Prevalence of long COVID in a national cohort: longitudinal measures from disease onset until 8 months' follow-up. Persistence of COVID-19 symptoms in nonhospitalized individuals beyond a few months has not been well characterized. In this longitudinal study from the Faroe Islands, we present prevalence of long COVID in mainly nonhospitalized patients who were followed up for up to 8 months.
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