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Novel Imidazole Liquid Crystals; Experimental and Computational Approaches. The liquid crystalline materials named ( E )-4-(2-(4-oxo-5,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)hydrazineylidene)methyl)phenyl and 4-(alkoxy)benzoate, In , were synthesized and their mesomorphic behaviors were examined. The chemical structures of the produced compounds were confirmed by Fourier-transform infrared spectroscopy (FT-IR), NMR, and elemental analysis. Differential scanning calorimetry (DSC) and polarized optical microscopy were used to investigate the mesomorphic properties of designed heterocyclic derivatives. All the compounds tested had suitable thermal stability and enantiotropic behavior of smectogenic temperature ranges. Furthermore, the enantiotropic smectic C phases were observed to cover all the homologues. Moreover, computational investigations corroborated the experimental findings of the mesomorphic behavior. The reactivity parameters were computed for the derivatives and linked with the experimental data. Theoretical calculations revealed that the polarizability of the studied series increases with the chain length, whereas the HOMO-LUMO energy gap or other reactivity descriptors were less sensitive to the size of the system. On the other hand, the predicted thermodynamic parameters revealed the size dependence of thermal stability of the compounds.
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Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential. Tacrine is a drug used in the treatment of Alzheimer's disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca 2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer's disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers' interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer's disease, as well as other neurological disorders like Parkinson's disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
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Switching from Tenofovir-Based Combination Therapy to Tenofovir Monotherapy in Multidrug-Experienced Chronic Hepatitis B Patients: a 5-Year Experience at Two Centers. Patients with chronic hepatitis B (CHB) who were administered tenofovir disoproxil fumarate (TDF)-based combination therapy after receiving multiple drugs are frequently switched to TDF monotherapy in South Korea. We evaluated the efficacy and safety of switching to TDF monotherapy from TDF-based combination therapy over 5 years. This was a retrospective study of multidrug-experienced CHB patients who switched from TDF-based combination therapy to TDF monotherapy after achieving a virologic response (VR; <20 IU/mL) at Konkuk University Hospital and Sanggye Paik Hospital. The biochemical response was defined as a normalized serum ALT level during follow-up. Each patient was assessed from the date of switching to TDF monotherapy to the date of the last follow-up over 5 years. A total of 39 patients who received at least one antiviral therapy before TDF-based combination therapy were analyzed. The median duration of VR before switching to TDF monotherapy was 18 months and the median duration of TDF monotherapy was 55 months. In this study, except for one patient who had poor compliance, all patients maintained a VR. Three patients had a temporarily increased HBV DNA level and 91.2% of the patients showed a biochemical response. Switching multidrug-experienced patients to TDF monotherapy is generally safe and effective.
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Prevalence and Correlates of Metabolic Syndrome and Its Components in Chinese Children and Adolescents Aged 7-17: The China National Nutrition and Health Survey of Children and Lactating Mothers from 2016-2017. This descriptive study aimed to determine the prevalence of metabolic syndrome (MetS) and its components among Chinese children and adolescents aged 7-17 from 2016-2017 according to the Cook's criteria modified for age on the basis of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and to evaluate the associations between the factors of interest (especially vitamin A, vitamin D and hyperuricemia) of MetS and its components, using data from the China National Nutrition and Health Survey of Children and Lactating Mothers from 2016-2017. A total of 54,269 school-aged children and adolescents were ultimately included in this study. Anthropometric measurements and laboratory examinations of the subjects and their relevant information were also collected. A multivariate logistic regression analysis model was applied to analyze the relationships between relevant factors associated with MetS and its components. In the present study, the prevalence of MetS in children and adolescents was 5.98%. Among the five components of MetS, elevated blood pressure (BP) and abdominal obesity were the most prevalent (39.52% and 17.30%), and 58.36% of the subjects had at least one of these components. In the multivariate logistic regression, an overweight condition, obesity and hyperuricemia were positively correlated with the incidence of MetS and all five components. There was also a positive association observed between vitamin A and the risk of MetS and some components of MetS (abdominal obesity and high triglycerides (TG)) and vitamin A was negatively associated with the risk of low high-density lipoprotein cholesterol (HDL-C). Subjects with vitamin D inadequacy had a higher risk of MetS (OR = 1.364, 95%CI: 1.240-1.500) and four of its components, excepting elevated FBG (fast blood glucose). Vitamin D deficiency was positively associated with MetS (OR = 1.646, 95%CI: 1.468-1.845) and all five of its components. Well-designed, large-scale prospective studies are also needed in the future.
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The therapeutic role of mesenchymal stem cell-derived exosomes in the autoimmune diseases. Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.
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The role of kappa opioid receptors in immune system - An overview. Opioids are one of the most effective anti-nociceptive agents used in patients with cancer pain or after serious surgery in most countries. The endogenous opioid system participates in pain perception, but recently its role in inflammation was determined. κ-opioid receptors (KOP receptors), a member of the opioid receptor family, are expressed in the central and peripheral nervous system as well as on the surface of different types of immune cells, e.g. T cells, B cells and monocytes. In this review, we focused on the involvement of KOP receptors in the inflammatory process and described their function in a number of conditions in which the immune system plays a key role (e.g. inflammatory bowel disease, arthritis, subarachnoid hemorrhage, vascular dysfunction) and inflammatory pain. We summed up the application of known KOP ligands in pathophysiology and we aimed to shed new light on KOP receptors as important elements during inflammation.
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continu medic educ question septemb articl titl efficaci safeti infliximab retreat crohn diseas multicent prospect observ cohort regain studi
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Disconjugacy of Eye Movements during Attempted Fixation: A Sufficient Marker for Amblyopia? To investigate whether detection of disconjugacy of eye movements during attempted fixation, or interocular position instability, may serve as a single sensitive test for amblyopia.
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The Association between Survivorship Care Plans and Patient-Reported Satisfaction and Confidence with Follow-Up Cancer Care Provided by Primary Care Providers. Survivorship care plans aim to facilitate a smooth transition from tertiary to primary care settings after primary cancer treatment is completed. This study sought to identify the sociodemographic factors associated with receiving a survivorship care plan and examine the relationship between receiving a plan and confidence in follow-up care delivered by primary care providers. A cross-sectional analysis of the Canadian Partnership Against Cancer's Experiences of Cancer Patients in Transition Study was conducted (n = 9970). Separate adjusted multinomial logistic regression models assessed the relationship between survivorship care plans and follow-up care outcomes. Proportion of survivors more likely to receive a survivorship care plan varied by numerous sociodemographic and medical factors, such as cancer type (colorectal and prostate), gender (male), and education (high school or less). In unadjusted and adjusted models, individuals who received a Survivorship Care Plan had significantly higher odds of: having felt their primary care providers were involved; agreeing that their primary care providers understood their needs, knew where to find supports and services, and were able to refer them directly to services; and were confident that their primary care provider could meet their follow-up care needs.
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Physico-chemical parameters of phase separation of the mixture of BSA and triton X 100 in aqueous solutions of monohydroxy compounds. Clouding behavior and thermodynamic properties for the TX 100 + BSA mixture were investigated in aqueous and aq. alcoholic media. In an aqueous environment, the values of cloud point (CP), at which a clear solution becomes cloudy, for TX 100 decreases with augmentation of the concentration of BSA. The reverse result was obtained in the aq. alcoholic media. In this study, we have used ethanol (EtOH), 1-propanol (1-PrOH), and 2-butanol (2-BuOH) as alcohols. The changes of CP values in alcoholic media have been obtained in the following order: CP H2O+EtOH > CP H2O+2-BuOH > CP H2O+1-PrOH . The standard free energy (∆G c o ), standard enthalpy (∆H c o ), and standard entropy (∆S c o ) changes of clouding were derived at CP. The ΔG c 0 values of TX 100 + BSA decreases in the aqueous and alcoholic media with increasing the concentration of BSA and alcohol. This process becomes endothermic in the aq. alcoholic media. Different thermodynamic properties of transfer and entropy-enthalpy compensation parameters for the phase partitioning of the TX 100 + BSA mixture have been calculated and assessed properly.
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Advances in Waveguide Bragg Grating Structures, Platforms, and Applications: An Up-to-Date Appraisal. A Bragg grating (BG) is a one-dimensional optical device that may reflect a specific wavelength of light while transmitting all others. It is created by the periodic fluctuation of the refractive index in the waveguide (WG). The reflectivity of a BG is specified by the index modulation profile. A Bragg grating is a flexible optical filter that has found broad use in several scientific and industrial domains due to its straightforward construction and distinctive filtering capacity. WG BGs are also widely utilized in sensing applications due to their easy integration and high sensitivity. Sensors that utilize optical signals for sensing have several benefits over conventional sensors that use electric signals to achieve detection, including being lighter, having a strong ability to resist electromagnetic interference, consuming less power, operating over a wider frequency range, performing consistently, operating at a high speed, and experiencing less loss and crosstalk. WG BGs are simple to include in chips and are compatible with complementary metal-oxide-semiconductor (CMOS) manufacturing processes. In this review, WG BG structures based on three major optical platforms including semiconductors, polymers, and plasmonics are discussed for filtering and sensing applications. Based on the desired application and available fabrication facilities, the optical platform is selected, which mainly regulates the device performance and footprint.
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Isotope tracing in health and disease. Biochemical characterization of metabolism provides molecular insights for understanding biology in health and disease. Over the past decades, metabolic perturbations have been implicated in cancer, neurodegeneration, and diabetes, among others. Isotope tracing is a technique that allows tracking of labeled atoms within metabolites through biochemical reactions. This technique has become an integral component of the contemporary metabolic research. Isotope tracing measures substrate contribution to downstream metabolites and indicates its utilization in cellular metabolic networks. In addition, isotopic labeling data are necessary for quantitative metabolic flux analysis. Here, we review recent work utilizing metabolic tracing to study health and disease, and highlight its application to interrogate subcellular, intercellular, and in vivo metabolism. We further discuss the current challenges and opportunities to expand the utility of isotope tracing to new research areas.
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An investigation into the detection of the pulse in conscious and anaesthetized dogs. To record the success rate of veterinary professionals and students at identifying the pulse in conscious and anaesthetized dogs. To explore the influence of clinical experience, pulse location, anaesthesia and likely confounding variables on the success of pulse palpation.
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Vasodilation of Pre-contracted Porcine Retinal Arteries by Carbonic Anhydrase Inhibitors with Enhanced Lipophilicity. In this study, we investigated the vasodilation properties on pre-contracted retinal arteries of a restricted series of carbonic anhydrase inhibitors (CAIs) of the sulfonamide type with enhanced lipophilicity, to assess if it affects the potency of CAIs as vasodilators.
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Spontaneous large liver haematoma with extensive intraperitoneal bleeding in a patient with COVID-19 infection. Thrombotic complications during COVID-19 infections occur frequently, and anticoagulants to prevent and treat deep vein thrombosis appear to have a good safety profile in these patients. In addition, haemorrhagic complications during COVID-19 infections have also been reported. Hepatic inflammation can occur in COVID-19 infections as a direct consequence of cellular infection and cytopathy. Spontaneous subcapsular hepatic haematoma is extremely rare and can be life-threatening.A woman in her 40s presented to the hospital with fever and shortness of breath and was diagnosed with COVID-19 infection with respiratory failure requiring intubation. On day 49 of hospitalisation, she developed melena and acute anaemia; her haemoglobin dropped from 97g/L (9.7g/dL) to 56g/L (5.6g/dL). Abdominal and pelvic CT scans showed a large subcapsular liver haematoma with retroperitoneal extension. The patient received blood transfusions and remained haemodynamically stable. She was eventually extubated and discharged home.
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Combined procedure with radial probe and convex probe endobronchial ultrasound. Concurrent bronchoscopy using radial probe and convex endobronchial ultrasound (RP- and CP-EBUS) is used to simultaneously evaluate both peripheral lung lesions for the histological diagnosis of the primary tumor and mediastinal lymph nodes for mediastinal staging. So far, little is known about the combined procedure with RP- and CP-EBUS.
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Assessment of Bacterial Isolates from the Urine Specimens of Urinary Tract Infected Patient. Urinary tract infections (UTIs) maintained a serious public health concern, as did the growth in antibiotic resistance both between uropathogenic microorganisms. A regular assessment of the microbiological agents that cause UTIs, as well as their antimicrobial resistance, is essential for a tailored empirical antibiotic response. Knowing the variables that cause UTIs can help you intervene quickly and simply to get the condition under control. The most common infecting species in acute infection is Escherichia coli (E. coli). To strengthen infection control strategies, it is necessary to know the prevalence and location of UTI. The goal of this research is to measure the frequency of microorganisms isolated from patients with UTIs as well as the antimicrobial sensitivity characteristics of Gram-negative bacteria. The purpose of this research has been to evaluate the frequency of UTIs by extracting and characterizing the various bacterial etiological organisms, as well as to assess the factors linked to UTIs. The goal of this research is to identify, characterize, and establish the antibiotic susceptibility patterns of bacteria linked to urinary tract infections. Fresh collected urine specimen was taken from inpatients or outpatients in UTI cases and bacteriologically tested using conventional microbiological methods. The Kirby-Bauer disc diffusion method was used to create the antibiogram. Staphylococcus saprophyticus, Staphylococcus aureus (28%), and Escherichia coli (24.6%) were the most common isolates (20%). The evaluated agents' antibacterial activity was all in the following order: cefixime, ciprofloxacin, augmentin, gentamicin, ceftazidime, nitrofurantoin, ofloxacin, and cefuroxime. It was discovered that each and every one of the microbes exhibited varied degrees of resistance to the antibiotics nitrofurantoin, ciprofloxacin, and ofloxacin. Every type of bacteria, with the exception of those belonging to the genus Streptococcus, has a Multiple Antibiotic Resistance Index (MARI) that is more than 0.2. The first-line therapies for urinary tract infections (UTIs) in the region would consist of ciprofloxacin, ofloxacin, and nitrofurantoin. Lower urinary tract infections almost never result in problems if they are diagnosed and treated as soon as possible and in the correct manner. However, if treatment is not sought, a urinary tract infection can lead to serious complications.
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People with COPD have greater participation restrictions than age-matched older adults without respiratory conditions assessed during the COVID-19 pandemic. Participation restriction has detrimental effects for older adults but it is unknown how participation differs for people with chronic obstructive pulmonary disease (COPD) compared to older adults of the same age without respiratory conditions. We compared scores on the Late Life Disability Instrument (LLDI) between people with COPD (study group) and a random sample of older adults (control group).
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Young Women Are Protected Against Vascular Insulin Resistance Induced by Adoption of an Obesogenic Lifestyle. Vascular insulin resistance is a feature of obesity and type 2 diabetes that contributes to the genesis of vascular disease and glycemic dysregulation. Data from preclinical models indicate that vascular insulin resistance is an early event in the disease course, preceding the development of insulin resistance in metabolically active tissues. Whether this is translatable to humans requires further investigation. To this end, we examined if vascular insulin resistance develops when young healthy individuals (n = 18 men, n = 18 women) transition to an obesogenic lifestyle that would ultimately cause whole-body insulin resistance. Specifically, we hypothesized that short-term (10 days) exposure to reduced ambulatory activity (from >10 000 to <5000 steps/day) and increased consumption of sugar-sweetened beverages (6 cans/day) would be sufficient to prompt vascular insulin resistance. Furthermore, given that incidence of insulin resistance and cardiovascular disease is lower in premenopausal women than in men, we postulated that young females would be protected against vascular insulin resistance. Consistent with this hypothesis, we report that after reduced ambulation and increased ingestion of carbonated beverages high in sugar, young healthy men, but not women, exhibited a blunted leg blood flow response to insulin and suppressed skeletal muscle microvascular perfusion. These findings were associated with a decrease in plasma adropin and nitrite concentrations. This is the first evidence in humans that vascular insulin resistance can be provoked by short-term adverse lifestyle changes. It is also the first documentation of a sexual dimorphism in the development of vascular insulin resistance in association with changes in adropin levels.
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Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma (PDAC) is a multifactorial disease, the molecular profile of which remains unclear. This study aimed at unveiling the disease-related protein networks associated with different outcomes of resectable, node-positive PDAC cases. We assessed laser-microdissected cancerous cells from PDAC tissues of a poor outcome group (POG; n = 4) and a better outcome group (BOG; n = 4). Noncancerous pancreatic duct tissues (n = 5) were used as the reference. We identified four representative network modules by applying a weighted network correlation analysis to the obtained quantitative PDAC proteome datasets. Two network modules that were significant for POG were associated with the heat shock response to hypoxia-related stress; in the latter, a large involvement of the non-canonical Hedgehog pathway (regulated by GLI1), the internal ribosome entry site-mediated cap-independent translation, the inositol requiring enzyme 1-alpha (IRE1α)/X-box binding protein 1 pathway of the unfolding protein response (UPR), and the aerobic glycolysis was observed. By contrast, the BOG characteristic module was involved in the inactivation of the UPR pathway via the synoviolin 1-dependent proteasomal degradation of IRE1α, the activation of SOX2, and the loss of PALB2 (partner and localizer of BRCA2) function, all potentially suppressing malignant tumor development. Our findings might facilitate future therapeutic strategies for PDAC.
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Prognosis of patients with cardiogenic shock following acute myocardial infarction: The difference between ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. Acute myocardial infarction (AMI) complicated by cardiogenic shock has high mortality and remains challenging even in the revascularization era. We conducted this study to understand patients' outcomes. We retrospectively analyzed electronic medical records data from 1175 patients with AMI complicated by cardiogenic shock that developed within 3 days of admission to a multicenter medical care system between January 1, 2000, and July 31, 2018. Patients with AMI were classified into the ST-segment elevation MI (STEMI) group or the non-ST-segment elevation MI (NSTEMI) group. The short-term and 1-year mortality and adverse events after index admission were analyzed via logistic regression and a Cox proportional hazards model. When compared with NSTEMI, patients with STEMI tended to be younger (65.68 ± 14.05 years vs 70.70 ± 12.99 years, P < .001), men (73.29% vs 60.87%, P < .001), and have fewer underlying chronic diseases. Short-term mortality at index hospitalization was 14.83% in the STEMI group and 21.30% in the NSTEMI group; long-term mortality was 17.06% for the STEMI group and 24.13% for the NSTEMI group. No difference was observed between the 2 groups for patients who developed a cerebral vascular accident during the admission period. However, the major and gastrointestinal bleeding rates were higher in the STEMI group (2.66% vs 0.22%, P = .014; 3.36% vs 0.22%, P = .007, respectively). Age and respiratory failure were the most significant risk factors for short-term mortality. Revascularization may be beneficial for the short-term outcome but did not reach significance in multivariable analysis. In patients with AMI with cardiogenic shock, NSTEMI was associated with a significantly higher mortality rate in short-term results.
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Diurnal Variation of Corneal Hysteresis in Patients With Untreated Primary Open Angle Glaucoma and Normal Individuals. Corneal hysteresis in both patients with untreated open angle glaucoma and normal individuals demonstrated significant diurnal variation independent of confounding factors and was higher in the nighttime than in the daytime.
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MD Simulation Studies for Selective Phytochemicals as Potential Inhibitors against Major Biological Targets of Diabetic Nephropathy. Diabetes is emerging as an epidemic and is becoming a public health concern worldwide. Diabetic nephropathy is one of the serious complications of diabetes, and about 40% of individuals with diabetes develop diabetic nephropathy. The consistent feature of diabetes and its associated nephropathy is hyperglycemia, and in some cases, hyperamylinemia. Currently, the treatment includes the use of medication for blood pressure control, sugar control, and cholesterol control, and in the later stage requires dialysis and kidney transplantation, making the management of this complication very difficult. Bioactive compounds, herbal medicines, and extracts are extensively used in the treatment and prevention of several diseases, and some are reported to be efficacious in diabetes too. Therefore, in this study, we tried to identify the therapeutic potential of phytochemicals used in in silico docking and molecular dynamic simulation studies using a library of 5284 phytochemicals against the two potential targets of type 2 diabetes-associated nephropathy. We identified two phytochemicals (i.e., gentisic acid and michelalbine) that target human amylin peptide and dipeptidyl peptidase-4, respectively, with good binding affinity. These phytochemicals can be further evaluated using in vitro and in vivo studies for their anti-hyperglycemia and anti-hyperamylinemia effects.
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Environmental enrichment: dissociated effects between physical activity and changing environmental complexity on anxiety and neurogenesis in adult male Balb/C mice. Several factors, including environmental modifications, stimulate neuroplasticity. One type of neuroplasticity consists in the generation of new neurons in the dentate gyrus of the hippocampus. Neurogenesis is modulated by environmental enrichment (ENR, tunnels plus running wheel) and affected by the time of exposure to ENR. Despite the wide use of ENR to stimulate neuroplasticity, the degree to which ENR variations modeled by temporally changing the level of environmental complexity affect hippocampal neurogenesis and anxiety is still unclear. Thus, we investigated the effects of five housing conditions on young adult male Balb/C mice exposed for 42 days. The groups were as follows: standard conditions without ENR, constant ENR complexity, gradual increase of ENR complexity followed by a gradual decrease of ENR complexity, gradual increase of ENR complexity followed by constant ENR complexity, and constant ENR complexity followed by a gradual decrease of ENR complexity. On day 44, mice were exposed to the elevated plus-maze to evaluate anxiety. Further, we analyzed neurogenesis and quantified corticosterone levels. In an additional experiment, we explored the effect of voluntary physical activity on anxiety, neurogenesis, and corticosterone during the variations in ENR complexity. Our results showed that any change in ENR complexity over time reduced anxiety. Also, voluntary physical activity alone or in the context of a complex environment increased doublecortin cell maturation in the granular cell layer of the hippocampus. Finally, our study supports that physical activity acts proneurogenic, whereas any change in environmental complexity decreases anxiety-like behavior. However, the decrease in corticosterone levels elicited by physical activity was lower than the decrease produced by the decrement in environmental complexity.
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Meeting report - Cell size and growth: from single cells to the tree of life. In April 2022, The Company of Biologists hosted their first post-pandemic in-person Workshop at Buxted Park Country House in the Sussex countryside. The Workshop, entitled 'Cell size and growth: from single cells to the tree of life', gathered a small group of early-career and senior researchers with expertise in cell size spanning a broad range of organisms, including bacteria, yeast, animal cells, embryos and plants, and working in fields from cell biology to ecology and evolutionary biology. The programme made ample room for fruitful discussions and provided a much-needed opportunity to discuss the most recent findings relating to the regulation of cell size and growth, identify the emerging challenges for the field, and build a community after the pandemic.
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Pilot Influenza Syndromic Surveillance System Based on Absenteeism and Temperature in China: Development and Usability Study. Shortcomings of the current school-based infectious disease syndromic surveillance system (SSS) in China include relying on school physicians to collect data manually and ignoring the health information of students in attendance.
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Dissonance in Young Adult Cigarillo Users' Categorization of Concept Flavored and Unflavored Products. This study asks young adult cigarillo users to categorize their preferred flavor in order to examine user consensus and potential methodological and regulatory implications of flavor name-based categorization systems. Young adult (21-28 years) cigarillo users ( n = 426) named and categorized their favorite cigarillo flavor into one of seven categories: Fruit, Sweet and Candy, Mint, Alcohol, Menthol, Tobacco, and Other. Flavor responses were coded as characterizing (ex: Grape, Wine) or concept (ex: Jazz, Diamond) flavors. Variation within and between categories was assessed, including the presence of concept flavors and the placement of flavors in multiple categories. Of the 66 unique flavor names provided, participants placed 20 (30.1%) in more than one flavor category. Most of the Tobacco (76.9%) and Other (69.2%) flavor names appeared in multiple categories. The majority of flavor names in the Tobacco (69.2%) and Other (61.5%) categories were concept flavors. Concept flavors were placed in multiple categories (45.0%) twice as often as characterizing flavors (23.9%). This study has identified dissonance among cigarillo users' flavor categorizations, particularly for concept flavored and unflavored products. Flavor names may obscure how and whether a product is flavored. Research on and regulation of flavored tobacco products should classify products by flavor additives rather than by name alone.
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Regulation of heme utilization and homeostasis in Candida albicans. Heme (iron-protoporphyrin IX) is an essential but potentially toxic cellular cofactor. While most organisms are heme prototrophs, many microorganisms can utilize environmental heme as iron source. The pathogenic yeast Candida albicans can utilize host heme in the iron-poor host environment, using an extracellular cascade of soluble and anchored hemophores, and plasma membrane ferric reductase-like proteins. To gain additional insight into the C. albicans heme uptake pathway, we performed an unbiased genetic selection for mutants resistant to the toxic heme analog Ga3+-protoporphyrin IX at neutral pH, and a secondary screen for inability to utilize heme as iron source. Among the mutants isolated were the genes of the pH-responsive RIM pathway, and a zinc finger transcription factor related to S. cerevisiae HAP1. In the presence of hemin in the medium, C. albicans HAP1 is induced, the Hap1 protein is stabilized and Hap1-GFP localizes to the nucleus. In the hap1 mutant, cytoplasmic heme levels are elevated, while influx of extracellular heme is lower. Gene expression analysis indicated that in the presence of extracellular hemin, Hap1 activates the heme oxygenase HMX1, which breaks down excess cytoplasmic heme, while at the same time it also activates all the known heme uptake genes. These results indicate that Hap1 is a heme-responsive transcription factor that plays a role both in cytoplasmic heme homeostasis and in utilization of extracellular heme. The induction of heme uptake genes by C. albicans Hap1 under iron satiety indicates that preferential utilization of host heme can be a dietary strategy in a heme prototroph.
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[Analysis of the provision of medical personnel in the subjects of the North Caucasus Federal District]. The article presents the results of a comparative analysis of the provision of medical personnel. Differences in the indicators of provision with specialists of various profiles have been studied. It is noted that in the North Caucasian Federal District the total values ​​of the medical service density indicator are lower than in the Russian Federation by 2.1%. The highest rates of provision with doctors are registered in the republics of Ingushetia with an increase of 32%, and in the republic of North Ossetia. Higher values ​​of the provision indicator with the heads of the organization and their deputies were established in the North Caucasus Federal District than in the Russian Federation. At the same time, in most subjects of the North Caucasus Federal District there is a shortage of specialists in the following specialties: anesthesiologists-resuscitators, pediatric surgeons, neonatologists, pediatricians, psychiatrists, radiologists, epidemiologists. However, the indicator of provision with dentists in the North Caucasus Federal District exceeded the Russian one by 2 times. Based on the analysis, the authors present recommendations, including the need to eliminate the shortage of doctors in a number of specialties, increase the admission to residency in them, strengthen social support measures, temporarily restrict the admission of applicants in the specialty of dentistry, etc.
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Formation and Parallel Manipulation of Gradient Droplets on a Self-Partitioning SlipChip for Phenotypic Antimicrobial Susceptibility Testing. Flexible, robust, and user-friendly screening systems with a large dynamic range are highly desired in scientific research, industrial development, and clinical diagnostics. Droplet-based microfluidic systems with gradient concentrations of chemicals have been demonstrated as promising tools to provide confined microenvironments for screening tests with small reaction volumes. However, the generation and manipulation of gradient droplets, such as droplet merging, generally require sophisticated fluidic manipulation systems, potentially limiting their application in decentralized settings. We present a gradient-droplet SlipChip (gd-SlipChip) microfluidic device that enables instrument-free gradient droplet formation and parallel manipulation. The device can establish a gradient profile by free interfacial diffusion in a continuous fluidic channel. With a simple slipping step, gradient droplets can be generated by a surface tension-driven self-partitioning process. Additional reagents can be introduced in parallel to these gradient droplets with further slipping operations to initiate screening tests of the droplets over a large concentration range. To profile the concentration in the gradient droplets, we establish a numerical simulation model and verify it with hydrogen chloride (HCl) diffusion, as tested with a dual-color pH indicator (methyl orange and aniline blue). As a proof of concept, we tested this system with a gradient concentration of nitrofurantoin for the phenotypic antimicrobial susceptibility testing (AST) of Escherichia coli . The results of our gd-SlipChip-based AST on both reference and clinical strains of E. coli can be indicated by the bacterial growth profile within 3 h and are consistent with the clinical culture-based AST.
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Multiparametric liver MRI for predicting early recurrence of hepatocellular carcinoma after microwave ablation. High early recurrence (ER) of hepatocellular carcinoma (HCC) after microwave ablation (MWA) represents a sign of aggressive behavior and severely worsens prognosis. The aim of this study was to estimate the outcome of HCC following MWA and develop a response algorithmic strategy based on multiparametric MRI and clinical variables.
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Toxicity Analysis of Mesoporous Polydopamine on Intestinal Tissue and Microflora. As a promising therapy, photothermal therapy (PTT) converts near-infrared (NIR) light into heat through efficient photothermal agents (PTAs), causing a rapid increase in local temperature. Considering the importance of PTAs in the clinical application of PTT, the safety of PTAs should be carefully evaluated before their widespread use. As a promising PTA, mesoporous polydopamine (MPDA) was studied for its clinical applications for tumor photothermal therapy and drug delivery. Given the important role that intestinal microflora plays in health, the impacts of MPDA on the intestine and on intestinal microflora were systematically evaluated in this study. Through biological and animal experiments, it was found that MPDA exhibited excellent biocompatibility, in vitro and in vivo. Moreover, 16S rRNA analysis demonstrated that there was no obvious difference in the composition and classification of intestinal microflora between different drug delivery groups and the control group. The results provided new evidence that MPDA was safe to use in large doses via different drug delivery means, and this lays the foundation for further clinical applications.
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Traditional Chinese medicine therapies for patients with knee osteoarthritis: A protocol for systematic review and network meta-analysis. Knee osteoarthritis (KOA) is a common cause of chronic musculoskeletal pain and disability as well as a socioeconomic burden on healthcare services globally. Numerous clinical trials indicated that traditional Chinese medicine (TCM) may effectively improve the clinical symptoms of KOA patients. However, the comparative efficacy and safety of different TCM therapies in patients with KOA is not yet clear. In order to evaluate the efficacy and safety of TCM for KOA, we will conduct a systematic review and network meta-analysis on the existing randomized controlled trials (RCTs).
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The RhoGAP-myosin Myo9b regulates ocular lens pit morphogenesis. During eye development the lens placode invaginates to form the lens pit. Further bending of lens epithelium and separation from ectoderm leads eventually to a spherical lens vesicle with enclosed extracellular fluid. Changes in epithelial morphology involve the actin cytoskeleton and its regulators. The myosin Myo9b is simultaneously an actin-based motor and Rho GTPase-activating protein that regulates actin cytoskeleton organization. Myo9b-deficient adult mice and embryos were analyzed for eye malformations and alterations in lens development.
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Effectiveness of Dry Needling and Ischemic Trigger Point Compression in the Gluteus Medius in Patients with Non-Specific Low Back Pain: A Randomized Short-Term Clinical Trial. The presence of latent myofascial trigger points (MTrPs) in the gluteus medius is one of the possible causes of non-specific low back pain. Dry needling (DN) and ischemic compression (IC) techniques may be useful for the treatment of these MTrPs.
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Pollination syndrome accurately predicts pollination by tangle-veined flies (Nemestrinidae: Prosoeca s.s.) across multiple plant families. The idea that a syndrome of floral traits predicts pollination by a particular functional group of pollinators remains simultaneously controversial and widely used because it allows plants to be rapidly assigned to pollinators. To test the idea requires demonstrating that there is an association between floral traits and pollinator type. I conducted such a test in the Cape Floristic Region of South Africa, by studying the pollination of eight plant species from six families that flower in spring and have scentless, actinomorphic, upwards-facing flowers, with orbicular petals all held in the same plane. The petals are brilliant-white with red-purple nectar guides. The tubes are short and hold small volumes of concentrated nectar, except in the rewardless Disa fasciata (Orchidaceae). Pollinators were photographed and captured, pollen loads were analysed and pollination networks were constructed. Consistent with the pollination syndrome hypothesis, the species with the defined syndrome shared a small group of pollinators. The most frequent pollinators belonged to a clade of four tangle-veined fly species with relatively short proboscises (Nemestrinidae: Prosoeca s.s.), while functionally similar Bombyliidae and Tabanidae played minor roles. Among the four Prosoeca species, only Prosoeca westermanni has been described, a result that highlights our ignorance about pollinators. The demonstration of an association between the syndrome of traits and pollination by this group of flies explains the repeated evolution of the syndrome across multiple plant families, and allows prediction of pollinators in additional species. More generally, the result validates the idea that the traits of organisms determine their ecology.
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Uptake and effects of psychological first aid training for healthcare workers' wellbeing in nursing homes: A UK national survey. Psychological First Aid is a brief intervention based on international guidance from the World Health Organisation. Free to access online training in the intervention was introduced during the COVID-19 pandemic in UK. We aimed to determine the uptake of Psychological First Aid training among healthcare workers in care homes in the UK and to assess its effects on their wellbeing.
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Alterations in bone marrow microRNA expression profiles on infection with avian pathogenic Escherichia coli. Avian pathogenic Escherichia coli (APEC) is one of the most common avian bacterial diseases globally. The bone marrow is a reservoir of immature immune cells. To elucidate the role of bone marrow microRNAs (miRNAs) in regulating the host response to APEC infection, we performed miRNA-seq to investigate alterations in the expression of bone marrow miRNAs in three groups of specific pathogen-free chickens: non-challenged (NC) and challenged with APEC for 12 h (C12) and 24 h (C24). Twenty and 19 differentially expressed miRNAs (fold change >2, P < 0.01) were identified on comparing the NC and C12 and the NC and C24 groups, respectively. On functional annotation analysis of target genes of differentially expressed miRNAs, we found that the gene ontology term "immune system process" was significantly enriched at both 12 h and 24 h; moreover, several important signaling pathways were triggered in response to APEC infection, such as MAPK, cGMP-PKG, Notch, and cAMP pathways. In addition, we performed reverse transcription quantitative real-time PCR (qRT-PCR) to validate the differential expression of miRNAs. qRT-PCR data were similar to the sequencing data. On constructing an miRNA-target gene network, gga-miR-2127, gga-miR-6643-5p, and gga-miR-6567-3p were found to potentially play a vital role in the immune process. Overall, our findings provide deeper insights into miRNA transcriptome changes involved in the immune response of the chicken bone marrow to APEC infection.
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Role of coupling distances in a coupled thalamocortical network in the treatment of epilepsy. The establishment of a recent theoretical model of a coupled cortical thalamic network is an important step in the spatiotemporal dynamics of the brain. However, choosing the coupling distances and parameters for deep brain stimulation remains a very challenging task. This study aimed to establish a coupled cortical thalamic model with uncertain coupling distances. Utilizing different pathways formed by the pyramidal neuronal population, thalamic reticular nucleus, and thalamic relay nucleus, we reduced epileptic seizures with spike-wave discharges (SWDs) at 2-4 Hz. In modelling terms, numerical simulations demonstrated that a combination (1/3, 1/9) of the left and right ventricles is the optimal coupling distance of the proposed model by analyzing the percentage of SWDs. In simulation terms, on the one hand, the number of SWDs is inversely proportional to the amplitude; on the other hand, the number of SWDs shows a U-shaped trend with the change in frequency. The present study provides an important theoretical basis and direction for the future treatment of absence epilepsy. In brief, our simulation results will hopefully provide some help to patients.
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First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Kuwait and evaluation of REBA MTB-MDR assay for rapid detection of MDR-TB. Early detection of Mycobacterium tuberculosis (Mtb) in clinical specimens, its susceptibility to anti-TB drugs and disruption of infection transmission to new hosts are essential components for global tuberculosis (TB) control efforts. This study investigated major Mtb genotypes circulating in Kuwait and evaluated the performance of REBA MTB-MDR (REBA) test in comparison to GenoType MTBDRplus (gMTBDR+) assay for rapid detection of resistance of Mtb to isoniazid and rifampicin (MDR-TB). M. tuberculosis isolates (n = 256) originating predominantly from expatriate patients during a 6-month period were tested by spoligotyping and a dendrogram was created by UPGMA using MIRU-VNTRplus software. Phenotypic drug susceptibility testing (DST) was performed by MGIT 960 system. Genotypic DST for isoniazid and rifampicin was done by REBA and gMTBDR+ assays. Spoligotyping assigned 188 (73.4%) isolates to specific spoligotype international type (SIT) while 68 isolates exhibited orphan patterns. All major M. tuberculosis lineages were detected and EAI, CAS and Beijing families were predominant. Phylogenetic tree showed 131 patterns with 105 isolates exhibiting a unique pattern while 151 isolates clustered in 26 patterns. Fifteen isolates were resistant to one/more drugs. REBA and gMTBDR+ detected isoniazid resistance in 11/12 and 10/12 and rifampicin resistance in 4/5 and 4/5 resistant isolates, respectively. The diversity of SIT patterns are highly suggestive of infection of most expatriate patients with unique Mtb strains, likely acquired in their native countries before their arrival in Kuwait. Both, REBA and gMTBDR+ assays performed similarly for detection of resistance of Mtb to isoniazid and rifampicin for rapid detection of MDR-TB.
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Novel Insights on Dietary Polyphenols for Prevention in Early-Life Origins of Hypertension: A Review Focusing on Preclinical Animal Models. Polyphenols are the largest group of phytochemicals with health benefits. Early life appears to offer a critical window of opportunity for launching interventions focused on preventing hypertension, as increasing evidence supports the supposition that hypertension can originate in early life. Although polyphenols have antihypertensive actions, knowledge of the potential beneficial action of the early use of polyphenols to avert the development of hypertension is limited. Thus, in this review, we first provide a brief summary of the chemistry and biological function of polyphenols. Then, we present the current epidemiological and experimental evidence supporting the early-life origins of hypertension. We also document animal data on the use of specific polyphenols as an early-life intervention to protect offspring against hypertension in adulthood and discuss underlying mechanisms. Continued research into the use of polyphenols to prevent hypertension from starting early in life will have far-reaching implications for future health.
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Influence of Dietary Salt Intake on T2D Treatment. To what extent patients undergoing long-term T2D treatment are affected by dietary salt intake has not been completely investigated.
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Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study. General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia.
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Single-frame 3D lensless microscopic imaging via deep learning. Since the pollen of different species varies in shape and size, visualizing the 3-dimensional structure of a pollen grain can aid in its characterization. Lensless sensing is useful for reducing both optics footprint and cost, while the capability to image pollen grains in 3-dimensions using such a technique could be truly disruptive in the palynology, bioaerosol sensing, and ecology sectors. Here, we show the ability to employ deep learning to generate 3-dimensional images of pollen grains using a series of 2-dimensional images created from 2-dimensional scattering patterns. Using a microscope to obtain 3D Z-stack images of a pollen grain and a 520 nm laser to obtain scattering patterns from the pollen, a single scattering pattern per 3D image was obtained for each position of the pollen grain within the laser beam. In order to create a neural network to transform a single scattering pattern into different 2D images from the Z-stack, additional Z-axis information is required to be added to the scattering pattern. Information was therefore encoded into the scattering pattern image channels, such that the scattering pattern occupied the red channel, and a value indicating the position in the Z-axis occupied the green and blue channels. Following neural network training, 3D images were formed from collated generated 2D images. The volumes of the pollen grains were generated with a mean accuracy of ∼84%. The development of airborne-pollen sensors based on this technique could enable the collection of rich data that would be invaluable to scientists for understanding mechanisms of pollen production climate change and effects on the wider public health.
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Photoelectron Storages in Functionalized Carbon Nitrides for Colorimetric Sensing of Oxygen. Colorimetric sensors have been widely used for centuries across diverse fields, thanks to their easy operation and uncompromisingly high sensitivity with no need for electricity. However, it is still a great challenge for conventional chromogenic systems to perform multiple measurements meanwhile maintaining high robustness. Here, we reported that carbon nitrides (CNs), the raw materials that are abundant, structure-tunable, and stable semiconductors with photoelectron storage capability, can be developed as a chromogenic system for colorimetric sensors. Beyond conventional metal oxides that only demonstrated a single blue-color switch after photoelectron storage, CN exhibited a multicolor switch under identical conditions owing to the unusual multiple photoelectron storage pathways. Mechanism studies revealed cyano and carbonyl groups in CN crucially elongated the centroid distance of electrons/holes, which exclusively stabilized the specific excited states that have different light absorption; meanwhile, the counter cations strengthened these processes. As a result, O 2 , a proof-of-concept analyte, was quantitatively detected by the CN-derived colorimetric sensor, showing high reversibility in hundreds of cycles and adaptable sensitivity/detection range, outperforming most reported and commercial oxygen sensors. These intriguing features of CN are highly envisioned for the next generation of colorimetric sensors, especially in developing countries or fieldworks, to improve the detection reliability and lower the sensing cost.
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On the choice of reference orbitals for linear-response calculations of solution-phase K-edge X-ray absorption spectra. The simplest response theory methods for computing vertical excitation spectra in condensed-phase are configuration interaction with single excitations (CIS) and linear-response time-dependent density functional theory (TDDFT) within the Tamm-Dancoff approximation. In applications to X-ray absorption spectroscopy (XAS), methods like CIS and TDDFT that codify only single excitations into the wave function are prone to catastrophic errors in main-edge and post-edge features whose shapes act as a crucial fingerprint in structural analyses of liquids. We show that these errors manifest primarily due to a lack of orbital relaxation in conventional linear-response theories and that core-ionized ( n - 1-electron) references, like those of electron-affinity TDDFT, can eliminate the errors in the spectral profile, even in the highest-energy parts of the post-edge. Crucially, we find that single excitations atop core-ionized references are sufficient to elucidate liquid-phase XAS spectra with semi-quantitative accuracy, opening the door for methods like electron-affinity CIS/TDDFT to be used as efficient alternatives to higher-order wave function approaches.
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Occupational exposure to particles and biomarkers of cardiovascular disease-during work and after vacation. Ambient particle matter is a risk factor for cardiovascular disease (CVD). However, little is known about associations between particles in occupational settings and risk of CVD. We investigated associations between occupational dust exposure and biomarkers of CVD, and potential recovery effects after vacation.
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3D-RISM-AI: A Machine Learning Approach to Predict Protein-Ligand Binding Affinity Using 3D-RISM. Hydration free energy (HFE) is a key factor in improving protein-ligand binding free energy (BFE) prediction accuracy. The HFE itself can be calculated using the three-dimensional reference interaction model (3D-RISM); however, the BFE predictions solely evaluated using 3D-RISM are not correlated to the experimental BFE for abundant protein-ligand pairs. In this study, to predict the BFE for multiple sets of protein-ligand pairs, we propose a machine learning approach incorporating the HFEs obtained using 3D-RISM, termed 3D-RISM-AI. In the learning process, structural metrics, intra-/intermolecular energies, and HFEs obtained via 3D-RISM of ∼4000 complexes in the PDBbind database (ver. 2018) were used. The BFEs predicted using 3D-RISM-AI were well correlated to the experimental data (Pearson's correlation coefficient of 0.80 and root-mean-square error of 1.91 kcal/mol). As important factors for the prediction, the difference in the solvent accessible surface area between the bound and unbound structures and the hydration properties of the ligands were detected during the learning process.
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Underweight and its associated factors among pediatrics attending HIV Care in South Gondar Zone public health facilities, Northwest Ethiopia, 2021. Malnutrition associated with HIV infection is a complex condition, with HIV-positive children having a higher mortality rate than HIV-negative children, resulting in significant morbidity and mortality in children. Data from a variety of situations are needed to counter this, but the evidence is limited, especially for the nutritional status of HIV-infected children. Therefore, this study aims to assess the magnitude of underweight and factors associated with it in children receiving antiretroviral therapy.
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Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study. The pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects.
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LGLNN: Label Guided Graph Learning-Neural Network for few-shot learning. Graph Neural Networks (GNNs) have been employed for few-shot learning (FSL) tasks. The aim of GNN based FSL is to transform the few-shot learning problem into a graph node classification or edge labeling tasks, which can thus fully explore the relationships among samples in support and query sets. However, existing works generally consider the graph learned by node features which ignore the initial pairwise label constraints and thus are generally not guaranteed to be optimal for FSL tasks. Also, existing works generally learn graph edges independently based on node's own features which lack of considering the consistent relationships among different edges. To address these issues, we propose a novel Label Guided Graph Learning-Neural network (LGLNN) model for FSL tasks. The aim of LGLNN is to incorporate the label information to learn an optimal metric graph for GNN by employing the pairwise constraint propagation. The main advantage of LGLNN is that it can learn the metrics (both similarity and dissimilarity) for each graph edge by aggregating the metric information from its neighboring edges and thus can conduct metric learning of all edges cooperatively and consistently. Experimental results demonstrate the effectiveness and better performance of the proposed LGLNN method.
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Medical students' perceptions and performance in an online regional anatomy course during the Covid-19 pandemic. The present study evaluated the students' psychological well-being, experiences, performance, and perception of learning regional anatomy remotely. A regional anatomy remote learning curriculum was designed and learning materials were delivered virtually to 120 undergraduate medical students at Jinan University, China. All the students consented and voluntarily participated in this study by completing self-administered online questionnaires including the Zung's Self-Rating Anxiety and Depression Scales at the beginning and end of the learning session. A subset participated in focus group discussions. Most of the students (90.0%) positively evaluated the current distance learning model. More than 80% were satisfied with the content arrangement and coverage. Many students preferred virtual lectures (68.2%) and videos showing dissections (70.6%) during the distance learning sessions. However, writing laboratory reports and case-based learning were the least preferred modes of learning as they were only preferred by 23.2% and 14.1% of the students, respectively. There was no significant lockdown-related anxiety or depression reported by students using depression and anxiety scales as well as feedback from focus group discussions. The surveyed students' confidence scores in distance learning were significantly higher after 5 weeks than at the beginning of the session (3.05 ± 0.83 vs. 3.70 ± 0.71, P < 0.05). Furthermore, the present results showed no significant differences between the current group's academic performance in the unit tests as well as the final overall evaluation for different parts of the course compared to that of the previous year's cohort. The findings above were congruent with focus group discussion data that the use of the online teaching platform for regional anatomy significantly improved the students' confidence in virtual and self-directed learning and did not negatively affect their academic performance.
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Accuracy of Brain Computed Tomography Diagnosis by Emergency Medicine Physicians. The objective of this study is to prospectively analyze emergency physicians' (EP's) abilities to interpret noncontrast computed tomography (NCCT) brain images in a blinded fashion and assess whether they can make medical decisions solely based on their interpretations.
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Whole-Body MRI in Limb Girdle Muscular Dystrophy Type R1/2A: Correlation With Clinical Scores. The most common limb girdle muscular dystrophy (LGMD) worldwide is LGMD type R1 (LGMDR1). The aim of this study was to correlate the MRI findings with functional scores and to describe the whole-body MRI (WBMRI) pattern in a LGMDR1 Brazilian cohort.
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Pharmacogenetic testing in pediatric neurology: a pragmatic study evaluating clinician and patient perceptions. Aim: To evaluate clinicians' and patients' perceptions of pharmacogenetic testing in a clinical setting. Materials & methods: This is a pragmatic mixed-method prospective observational study. Hospital pharmacists and neurologists participated in focus groups regarding pharmacogenetic testing; patients who received pharmacogenetic testing and their community pharmacists completed surveys to assess their perception of these tests. Results: Most study participants had a positive view of pharmacogenetic testing. Three major themes were identified from the focus groups: receptiveness to pharmacogenetic testing, pharmacogenetic test characteristics and integrating pharmacogenetic tests into practice. Conclusion: The views reported are encouraging for the eventual implementation of pharmacogenetics in practice. Local integration of these tests is an essential step to improve patient care through personalized medicine.
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Genomic analysis of single nucleotide polymorphisms in malaria parasite drug targets. Malaria is a life-threatening parasitic disease caused by members of the genus Plasmodium. The development and spread of drug-resistant strains of Plasmodium parasites represent a major challenge to malaria control and elimination programmes. Evaluating genetic polymorphism in a drug target improves our understanding of drug resistance and facilitates drug design. Approximately 450 and 19 whole-genome assemblies of Plasmodium falciparum and Plasmodium vivax, respectively, are currently available, and numerous sequence variations have been found due to the presence of single nucleotide polymorphism (SNP). In the study reported here, we analysed global SNPs in the malaria parasite aminoacyl-tRNA synthetases (aaRSs). Our analysis revealed 3182 unique SNPs in the 20 cytoplasmic P. falciparum aaRSs. Structural mapping of SNPs onto the three-dimensional inhibitor-bound complexes of the three advanced drug targets within aaRSs revealed a remarkably low mutation frequency in the crucial aminoacylation domains, low overall occurrence of mutations across samples and high conservation in drug/substrate binding regions. In contrast to aaRSs, dihydropteroate synthase (DHPS), also a malaria drug target, showed high occurrences of drug resistance-causing mutations. Our results show that it is pivotal to screen potent malaria drug targets against global SNP profiles to assess genetic variances to ensure success in designing drugs against validated targets and tackle drug resistance early on.
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Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient. Valproic acid (VPA) is an effective first-line anticonvulsant that is associated with several side effects including bone marrow suppression and subsequent cytopenia. However, VPA associated myelodysplasia is not a well described entity that can be seen in patients on VPA treatment.
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Comparison of the push-out bond strength of AH Plus sealer to dentin after using different herbal irrigation solutions as the final rinse. The aim of the present study was to evaluate the push-out bond strength of AH Plus sealer to dentin treated with the essential oils of Cumimum cyminum and Cinnamomum zeylanicum as herbal final irrigants. Forty human mandibular first premolars were selected. After smear layer removal, the samples were divided into 4 groups and irrigated with experimental solutions for 1 min and later with distilled water. G1: Cinnamomum zeylanicum (CZ) in minimum inhibitory concentration (MIC); G2: Sodium hypochlorite 2.5%; G3: Sodium hypochlorite in MIC; G4: Cuminum cyminum (CC) in MIC. After obturation, the roots were sectioned in order to obtain 1-mm discs for push-out assessment. The push-out test was performed using a universal testing machine. The slices were examined using a stereomicroscope at 30× to determine the mode of failure. The data were analyzed using one-way analysis of variance and Tukey's post-hoc test. The teeth irrigated with CZ showed significantly lower push-out resistance than those irrigated with NaOCl 2.5% and NaOCl at MIC. The other groups had no significant difference. The modes of failure were predominantly mixed. Under the limitations of the present study, CC does not have adverse effects on the bond strength of AH Plus and can be used as a good alternative for currently used final irrigants.
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Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling. Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.
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Non-canonical EphA2 activation underpins PTEN-mediated metastatic migration and poor clinical outcome in prostate cancer. The key process of mesenchymal to amoeboid transition (MAT), which enables prostate cancer (PCa) transendothelial migration and subsequent development of metastases in red bone marrow stroma, is driven by phosphorylation of EphA2 S897 by pAkt, which is induced by the omega-6 polyunsaturated fatty acid arachidonic acid. Here we investigate the influence of EphA2 signalling in PCa progression and long-term survival.
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Religious and Non-Religious Workplace Mobbing Victims: When Do People Turn to Religious Organisations? Researchers' interest in the impact of religious-spiritual assistance on victims of violence has increased in recent decades; however, factors that are relevant to workplace mobbing victims who seek such assistance remain poorly investigated. The purpose of this study is to highlight the factors that make spiritual assistance of religious organizations acceptable to religious and non-religious workplace mobbing victims. The study involved 463 adults working in Lithuanian organizations, of whom 79.5 per cent indicated that they were religious. ANOVA and Chi-square tests revealed that the significant factors were similarity of personal and religious values, the relation with the person providing assistance, and the circumstances characterising assistance. This study promotes further scientific discussion on the involvement of religious organizations in helping victims of workplace mobbing and explains why religious and non-religious individuals seeking assistance turn to religious organizations. The article presents only a part of the research results of the implemented project.
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Photothermal nanofibrillar membrane based on hyaluronic acid and graphene oxide to treat Staphylococcus aureus and Pseudomonas aeruginosa infected wounds. Here we reported the fabrication of an electrospun membrane based on a hyaluronic acid derivative (HA-EDA) to be used as a bandage for the potential treatment of chronic wounds. The membrane, loaded with graphene oxide (GO) and ciprofloxacin, showed photothermal properties and light-triggered drug release when irradiated with a near-infrared (NIR) laser beam. Free amino groups of HA-EDA derivative allowed autocrosslinking of the electrospun membrane; thus, a substantial enhancement in the hydrolytic resistance of the patch was obtained. In vitro antibacterial activity studies performed on Staphylococcus aureus and Pseudomonas aeruginosa revealed that such electrospun membranes, due to the synergistic effect of the antibiotic and NIR-mediated hyperthermia, reduced the viability of both pathogens. Specific in vitro experiment demonstrated also that is possible to disrupt, through laser irradiation, the biofilms formed onto the membrane.
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"I had so many life-changing decisions I had to make without support": a qualitative analysis of women's pregnant and postpartum experiences during the COVID-19 pandemic. The COVID-19 pandemic has posed profound challenges for pregnant patients and their families. Studies conducted early in the pandemic found that pregnant individuals reported increased mental health concerns in response to pandemic-related stress. Many obstetric practices changed their healthcare delivery models, further impacting the experiences of pregnant patients. We conducted a survey study to explore the ways in which COVID-19 impacted the lives of pregnant and newly postpartum people.
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Changes in litter input exert divergent effects on the soil microbial community and function in stands of different densities. Soil microbial communities influence soil biogeochemical cycling by affecting the production of extracellular enzymes and the release of carbon dioxide. Changes in litter input or stand density due to thinning can affect soil microbial communities and their function by altering soil biochemical properties. However, it is unclear how or to what extent different amounts of litter input affect soil microbial communities and their function in forest stands with different densities. Therefore, we simulated litter removal, 50 % litter reduction, normal litter input, and double litter increase under field conditions by applying different amounts of litter to soils with different stand densities in the laboratory. We then measured soil biochemical properties, microbial communities, enzyme activity, and respiration rate. Our results revealed that the responses of soil dissolved organic carbon and total nitrogen to litter input were more pronounced in the high-density forest stand with poor soil than in the low-density forest stand with nutrient-rich soil, which was mainly reflected in that the addition of litter significantly decreased the concentration of dissolved organic carbon while increasing the content of total nitrogen in the soil of the high-density forest stand. In comparison to the soil carbon component, the nitrogen component of the soil was more affected by stand density. The responses of soil fungal and bacterial communities to leaf litter treatment varied with stand density, as reflected primarily in changes in the relative abundances of Ascomycota, unclassified_K_fungi, and Proteobacteria, and changes in the relative abundances of their functional groups (ectomycorrhizal fungi, saprophytic fungi, pathogens, parasites, and bacteria involved in the nitrogen cycle). Soil fungal community responses to changes in litter input are more sensitive in the high-density forest with nutrient-poor soil than in the low-density forest stand. Furthermore, litter input inhibited the activities of soil β-glucuronidase, N-acetyl-β-d-glucosaminidase, and acid phosphatase more strongly in the low-density forest stand. Litter manipulation primarily affected enzymatic activity in the high-density forest stand by changing the diversity and composition of the soil fungal community. However, in the low-density forest stand, litter treatment affected soil enzyme activity, primarily through changes in soil bacterial and fungal community composition, as well as soil respiration through changes in bacterial richness (Chao 1) and community composition. We conclude that how the change in litter input impacts the soil microbial community and its function, or the magnitude of the effects, is largely dependent on soil quality. Relationships among soil variables, microbial communities, and function differ between stand densities. Our study contributes to an enhanced understanding of the impact of changes in litter input due to climate change or anthropogenic activities on soil biogeochemical cycles and can also guide rationally formulating forest management approaches to improve microbial function under climate change.
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Identification and molecular characterization of penicillin-nonsusceptible Streptococcus pneumoniae isolates recovered from invasive infections in a pre-pneumococcal vaccine era. Given the significant role of penicillin-nonsusceptible Streptococcus pneumoniae in inducing severe infectious diseases, identifying serotypes and genotypes that can mediate antimicrobial resistance has become a pillar of treatment strategies. This study aims to determine the correlation between the minimum inhibitory concentration of antimicrobial agents and amino acid mutations in penicillin-binding proteins. Moreover, molecular serotyping and multiple-locus variable number tandem repeat analysis typing were first-ever performed to characterize the invasive penicillin-nonsusceptible S. pneumoniae isolates in Iran.
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Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal cancer by regulating inflammation. Ulcerative colitis-associated colorectal cancer (UC-CRC) is an important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is a critical regulator for developmental events and cellular biological processes. However, the role of Pou3f1 in the development of UC-CRC is unclear.
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Porphyrin COF and its mechanical pressing-prepared carbon fiber hybrid membrane for ratiometric detection, removal and enrichment of Cd 2 . A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd 2+ due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cd 2+ coordination, and the resulting optical signal changes make the ratiometric detection of Cd 2+ possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd 2+ removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd 2+ removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd 2+ , and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs.
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Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis <em>via</em> NF-κB signaling pathway. HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive feedback loop for synovial inflammation and cartilage degradation. The aim of this study was to explore the role of HMGB1 in inflammation and catabolism of temporomandibular joint osteoarthritis (TMJOA) and whether inhibition of HMGB1 affects TMJOA. Human synovial fibroblasts were incubated with HMGB1, the expression of pro-inflammatory cytokines and catabolic mediators were measured by Western blot and ELISA. NF-κB signaling pathway involvement was studied by the NF-κB inhibitor and detected by Western blotting and immunofluorescence staining. TMJOA was induced by an injection of Complete Freund's adjuvant (CFA) into anterosuperior compartment of rat's joint. An anti-HMGB1 antibody was used to assess the effect to HMGB1 in the synovium and cartilage of the CFA-induced TMJOA rats by H&E, Safranin O, Masson trichrome staining, immunohistochemistry and immunofluorescence. HMGB1 markedly increased the production of MMP13, ADAMTS5, IL-1β and IL-6 through activating NF-κB signaling pathway in human synovial fibroblasts. In vivo, application of the HMGB1 neutralizing antibody effectively ameliorated the detrimental extent of TMJOA. Furthermore, the HMGB1 neutralizing antibody reduced the expression of NF-κB, pro-inflammatory cytokines and catabolic mediators in the synovium and cartilage of CFA-induced TMJOA rats. HMGB1 inhibition alleviates TMJOA by reducing synovial inflammation and cartilage catabolism possibly through suppressing the NF-κB signaling pathway and may become a therapeutic method against TMJOA.
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Payments for environmental services strategy for transboundary air pollution: A stochastic differential game perspective. Air pollution has become a global threat to societal development. The main challenges of transboundary air pollution control include two perspectives: uneven socioeconomic development of regions and the diffusion of air pollution. This paper proposes an PES strategy to alleviate transboundary air pollution by coordinating regional economic interests and environmental preferences within the joint prevention and control of air pollution region. To make the model design more realistic, we introduce the stochastic differential game model to characterize the diffusion and uncertainty of air pollution. The optimal feedback Nash equilibrium is derived in three PES scenarios (no PES, dynamic PES, and fixed-fee PES) by using the Hamilton-Jacobi-Bellman equation. Numerical simulations and sensitivity analysis are implemented to compare the optimal strategies under the three PES scenarios. The dynamic PES strategy is shown to outperform the no PES strategy and the fixed-fee PES strategy by encouraging the backward region to cut more emissions. Besides, the confidence interval theory is used to estimate the variation range of air pollution stocks, which provides a powerful diagnostic tool for policy-makers.
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Epimesatines A-I, nine undescribed prenylated flavonoids with SPHK1 inhibitory activities from Epimedium sagittatum maxim. Epimesatines A-I, nine undescribed prenylated flavonoids, along with ten known analogues, were isolated from the aerial parts of Epimedium sagittatum Maxim. The structures and absolute configurations of epimesatines A-I were determined using a combination of spectroscopic data, Rh 2 (OCOCF 3 ) 4 -induced electronic circular dichroism (ECD) experiments, ECD comparisons, and X-ray crystallography analysis. Epimesatines A and I displayed notable activities on the viabilities of human non-small cell lung cancer (NSCLC) A549 cells with IC 50 values of 1.77 and 9.97 μM, respectively. Furthermore, epimesatines A and I significantly inhibited the expression of sphingosine kinase 1 (SPHK1) in A549 cells. In addition, none of these compounds showed obvious toxicity on normal human lung bronchial epithelial BEAS-2B cells.
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Sexual Communication between Adolescent Partners: A Scoping Review and Directions for Future Research. Sexual communication between adolescent partners is an important component of sexual health and wellbeing. Over 40 years of research on adolescent sexual communication has yielded rich information, yet there remain gaps in our understanding of the communication process. The purpose of this scoping review was to synthesize the body of research on adolescent sexual communication to identify how communication has been conceptualized, how researchers have measured communication, and what theoretical frameworks have been applied across the literature. We identified 198 assessments of sexual communication across 119 quantitative studies. This work included 127,489 adolescents (<i>M</i><sub>age</sub> = 15.97) from 15 countries (81.5% U.S.-based). Most studies relied on self-reports (93.4%) and surveyed only one member of a couple (97.5%). The definition of sexual communication was highly varied across the literature: in half of assessments (52.0%) sexual communication was operationalized as a behavior-the verbal or nonverbal exchange of messages about sex-whereas the remaining half of assessments captured social-cognitive aspects of communication (e.g., communication self-efficacy, fear/anxiety). There was also a tendency for investigators to create their own idiosyncratic instruments: half of studies (48.9%) used instruments created by the research team with limited or no discussion of reliability/validity. Regarding the topic of communication, a third of assessments (33.8%) focused exclusively on condom communication and another quarter (24.0%) focused on other safer-sex issues (e.g., STDs, abstinence). Notably absent were studies focused on communication surrounding consent or sexual pleasure. Also absent was a guiding conceptual model or theory that could unify this body of work. Overall, results highlight gaps and inconsistencies in how partner sexual communication has been conceptualized, measured, and theorized about in previous work. We provide several recommendations for future theory-building efforts as well as rigorous, multimethod empirical investigations of adolescent sexual communication that would further our understanding of this important aspect of adolescent sexual wellbeing.
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STIM Proteins and Regulation of SOCE in ER-PM Junctions. ER-PM junctions are membrane contact sites formed by the endoplasmic reticulum (ER) and plasma membrane (PM) in close apposition together. The formation and stability of these junctions are dependent on constitutive and dynamic enrichment of proteins, which either contribute to junctional stability or modulate the lipid levels of both ER and plasma membranes. The ER-PM junctions have come under much scrutiny recently as they serve as hubs for assembling the Ca 2+ signaling complexes. This review summarizes: (1) key findings that underlie the abilities of STIM proteins to accumulate in ER-PM junctions; (2) the modulation of Orai/STIM complexes by other components found within the same junction; and (3) how Orai1 channel activation is coordinated and coupled with downstream signaling pathways.
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Microinvasive breast cancer and the role of sentinel lymph node biopsy. Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making. Our study included 72 MIBC patients with a mean patient follow-up time of 55 months. Three patients with MIBC had recurrence, and two deceased, leaving five patients in total with poor long-term outcomes and a DFS rate of 93.1%. Performing mastectomy, high nuclear grade, and negativity for ER and HER-2 were found to be associated with the use of SLNB, although none of these variables were found to be associated with DFS. One positive lymph node case was discovered following SLNB in our study. This suggests the use of SLNB may provide diagnostic information to some patients, although these are the anomalies. When comparing patients who had undergone SLNB to those which had not there was no difference in DFS. Certainly, the use of SLNB in MIBC is quite the conundrum. It is important to acknowledge that surgical complications have been reported, and traditional metrics used for risk assessment in invasive breast cancer may not hold true in the setting of microinvasion.
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Mutation spectrum in a cohort with familial exudative vitreoretinopathy. To expand the mutation spectrum of patients with familial exudative vitreoretinopathy (FEVR) disease.
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[Impacts of biochar and phosphorus application on soil phosphorus availability and soybean phosphorus uptake]. Biochar is beneficial to soil phosphorus (P) availability and crop growth, but the effects vary greatly across different soil types. We investigated the effects of rice straw biochar (4% of total mass) and P application (0, 30, and 90 kg P·hm -2 ) on soil P availability, phosphomonoesterase activity, and soybean P uptake by using lateritic red soil (pH 4.91) and cinnamon soil (pH 7.24) as test materials. The results showed that biochar application at different P levels significantly increased available P and total P in both soils. Biochar application with 30 kg P·hm -2 increased soil available P with maxima at 192.6% and 237.1% in lateritic red soil and cinnamon soil, respectively. Biochar application with 30 kg P·hm -2 in lateritic red soil significantly increased the activity of alkaline phosphomonoesterase by 78.9%, decreased the content of active organic P by 39.3%, and subsequently stimulated soybean P absorption and growth. Biochar amendment significantly reduced active organic P content in cinnamon soil, but did not affect soil phosphomonoesterase activity and plant growth. The content of active organic P was significantly negatively correlated with soil available P content. In summary, the effect of biochar on soil P availability varied across different soil types (lateritic red soil > cinnamon soil) and P levels (better at 30 kg P·hm -2 ). Our results could provide scientific basis for a promising application of biochar in reducing the amount of P fertilizer and increasing soybean P uptake, especially in lateritic red soil.
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Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines. Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines.
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Phylogenomic analysis of the bowfin (Amia calva) reveals unrecognized species diversity in a living fossil lineage. The Bowfin (Amia calva), as currently recognized, represents the sole living member of the family Amiidae, which dates back to approximately 150 Ma. Prior to 1896, 13 species of extant Bowfins had been described, but these were all placed into a single species with no rationale or analysis given. This situation has persisted until the present day, with little attention given to re-evaluation of those previously described nominal forms. Here, we present a phylogenomic analysis based on over 21,000 single nucleotide polymorphisms (SNPs) from 94 individuals that unambiguously demonstrates the presence of at least two independent evolutionary lineages within extant Amia populations that merit species-level standing, as well as the possibility of two more. These findings not only expand the recognizable species diversity in an iconic, ancient lineage, but also demonstrate the utility of such methods in addressing previously intractable questions of molecular systematics and phylogeography in slowly evolving groups of ancient fishes.
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Associations between cardiorespiratory fitness, monocyte polarization, and exercise-related changes in mnemonic discrimination performance in older adults. Biological aging is accompanied by a chronic pro-inflammatory state that may facilitate losses in hippocampal-dependent mnemonic discrimination. Aerobic exercise training promotes adaptations that include improved immune competency, higher cardiorespiratory fitness, and maintenance of hippocampal function. However, it is poorly understood whether, in active older adults, baseline immune cell profiles and cardiorespiratory fitness are possible mechanisms that facilitate the long-term benefits to hippocampal dependent mnemonic discrimination performance. This within-subjects study with counterbalanced conditions aimed to investigate whether baseline monocyte polarization and cardiorespiratory fitness influenced performance in the mnemonic similarity task (MST) and related Lure Discrimination Index (LDI) score after an acute bout of exercise. Twenty-one active older adults (M = 68 ± 5 yrs) underwent baseline testing in which blood samples were collected and cardiorespiratory fitness measured. Participants then returned and completed a seated rest or moderate intensity aerobic exercise condition in which the MST was proctored prior to and 5 min after each condition. A linear mixed effects model was used in which Participant ID was a random effect and Condition (rest v. exercise), Time (pre- v post-), and order were fixed main effects. Simple linear regression models were used to determine the variance accounted for by monocyte phenotypes and cardiorespiratory fitness for LDI scores post-condition. Post-rest LDI scores were significantly lower than post-exercise LDI scores (t(20) = -2.65, p < 0.02, d = -0.57). Intermediate monocytes were significant predictors of the change in pre- to post-exercise LDI scores (F(1, 19) = 6.03, p = 0.024, R 2 = 0.24) and cardiorespiratory fitness was a significant predictor of the difference between post-condition LDI scores (F(1, 19) = 6.71, p = 0.018, R 2 = 0.26). Our results suggest baseline cardiorespiratory fitness and intermediate monocytes may relate to the integrity of hippocampal-dependent mnemonic discrimination performance, and possibly the degree of responsiveness to aerobic exercise interventions.
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Microbial community in resistant and susceptible Churra sheep infected by Teladorsagia circumcincta. Gastrointestinal nematodes (GIN) are a major threat to health and welfare in small ruminants worldwide. Teladorsagia circumcincta is a nematode that inhabits the abomasum of sheep, especially in temperate regions, causing important economic losses. Given that T. circumcincta and microbiome share the same niche, interactions between them and the host are expected. Although it is known that within a sheep breed there are animals that are more resistant than others to infection by GIN, it is not known if the microbiome influences the phenotype of these animals. Under this condition, 12 sheep were classified according to their cumulative faecal egg count (cFEC) at the end of a first experimental infection, 6 as resistant group (RG) and 6 as susceptible group (SG) to T. circumcincta infection. Then, all sheep were experimentally infected with 70,000 L3 of T. circumcincta and at day 7 days post-infection were euthanized. At necropsy, gastric mucosa and gastric content from abomasum were collected to extract bacterial DNA and sequence V3-V4 region from 16S rRNA gene using Ilumina technology. After bioanalysis performed, results showed that α-diversity and β-diversity remained similar in both groups. However, resistant phenotype sheep showed a higher number of bacteria butyrate-fermenting species as Clostridium sensu stricto 1 (abundance in RG: 1.29% and in SG: 0.069%; p = 0.05), and Turicibacter (abundance in RG: 0.31% and in SG: 0.027%; p = 0.07) in gastric content but also Serratia spp in gastric mucosa (abundance in RG: 0.12% and in SG: 0.041%; p = 0.07). A trend towards a significant negative correlation between cFEC and Clostridium sensu stricto 1 abundance in gastric content was detected (r = - 0.537; p = 0.08). These data suggest that microbiome composition could be another factor associated with the development of the resistant phenotype modifying the interaction with the host and the in last instance affecting the individual risk of infection.
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Patient-Centred Outcomes Following Open Carpal Tunnel Release: A Systematic Review of the Current Literature. Background: Patients' individual interpretations of their own health outcomes are becoming increasingly important metrics in defining clinical success across all specialties, especially in hand surgery. However, there is a relative paucity of data using validated health-related quality of life (HR-QoL) assessments for carpal tunnel release (CTR). The purpose of this study was to review published outcomes on traditional open CTR to formally assess the current need for more accurate, validated assessment tools to evaluate CTR-specific HR-QoL. Methods: PubMed, MEDLINE and Cochrane Library databases were queried according to PRISMA guidelines for all studies investigating patient-reported outcomes following traditional open CTR. Analysis focused on HR-QoL, symptomatic relief, functional status, overall satisfaction and return to work or activities of daily living (ADLs). Results: In total, 588 unique articles were screened, and 30 studies met selection criteria. HR-QoL was formally assessed in only 3 studies using the validated 36-Item Short Form Survey. Symptomatic relief was measured in 29 (97%) studies, making it the most frequently reported item, whereas functional ability was reported by 19 (63%) studies. The Boston Carpal Tunnel Questionnaire was the most frequently utilised tool to assess symptomatic relief (13/30) and functional improvement (11/30). Using unvalidated custom surveys, 14 studies (47%) reported patient satisfaction and 12 studies (40%) documented time to return to work/ADLs. Conclusion: There is a dearth of studies utilising HR-QoL assessment tools to evaluate outcomes following traditional open CTR. The creation and validation of new CTR-specific HR-QoL tools accounting for both physical and psychological health is warranted. Level of Evidence: Level II (Therapeutic).
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Recovering individual haplotypes and a contiguous genome assembly from pooled long-read sequencing of the diamondback moth (Lepidoptera: Plutellidae). The assembly of divergent haplotypes using noisy long-read data presents a challenge to the reconstruction of haploid genome assemblies, due to overlapping distributions of technical sequencing error, intralocus genetic variation, and interlocus similarity within these data. Here, we present a comparative analysis of assembly algorithms representing overlap-layout-consensus, repeat graph, and de Bruijn graph methods. We examine how postprocessing strategies attempting to reduce redundant heterozygosity interact with the choice of initial assembly algorithm and ultimately produce a series of chromosome-level assemblies for an agricultural pest, the diamondback moth, Plutella xylostella (L.). We compare evaluation methods and show that BUSCO analyses may overestimate haplotig removal processing in long-read draft genomes, in comparison to a k-mer method. We discuss the trade-offs inherent in assembly algorithm and curation choices and suggest that "best practice" is research question dependent. We demonstrate a link between allelic divergence and allele-derived contig redundancy in final genome assemblies and document the patterns of coding and noncoding diversity between redundant sequences. We also document a link between an excess of nonsynonymous polymorphism and haplotigs that are unresolved by assembly or postassembly algorithms. Finally, we discuss how this phenomenon may have relevance for the usage of noisy long-read genome assemblies in comparative genomics.
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Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation. Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.
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Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats. Neuropathic pain (NP) arises as a direct consequence of traumatic spinal cord injury (SCI), which leads to devastating consequences for people suffering from this condition since no specific treatment has been defined. One relevant mechanism in generating painful stimuli involves the direct participation of reactive oxygen species (ROS) at the cellular and subcellular levels. Cannabidiol (CBD) is one of the two most crucial cannabinoid components of the cannabis plant and has been proposed as a potential treatment for NP. Its antioxidant, neuroprotective and anti-inflammatory properties have been documented. However, there is insufficient evidence regarding CBD as treatment of NP induced by SCI or the mechanisms that underlie this effect. In this study, we evaluated the antinociceptive effect of CBD as an acute treatment after the nociceptive behaviors characteristic of NP were established (hypersensitivity threshold and hypersensitivity response). Furthermore, the participation of oxidative stress was determined by lipid peroxidation (LP) and glutathione concentration (GSH) in female Wistar rats with SCI. Acute treatment with CBD (2.5-20 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH concentration in injured tissue 15 days after injury. The findings of this study suggest that the antinociceptive effect induced by CBD is regulated by reducing oxidative stress by decreasing the LP and increasing the concentration of antioxidant (GSH) defenses.
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DNA hypomethylation activation Wnt/TCF7L2/TDRD1 pathway promotes spermatogonial stem cell formation. Detailed analysis of the regulatory mechanism of spermatogonia stem cell (SSCs) genesis can provide a novel strategy for the application of SSCs in the fields of transgenic animal production and regenerative medicine. Previous studies in this study showed that WNT signaling can positively regulate the formation of SSCs, but the exact regulatory mechanism is not clear. Here, we predicted the target gene of the Wnt/TCF7L2 pathway, namely TDRD1, by bioinformatics analysis. Functional studies revealed that overexpression of TDRD1 during RA-induced SSCs formation in vitro significantly upregulated the expression of reproductive marker genes (Integrinβ1 and Integrinα6), and further flow cytometric analysis also confirmed that the formation efficiency of SSCs was significantly increased after overexpression of TDRD1; while interference with TDRD1 showed the exact opposite result. The in vivo experiments were consistent with the results of the in vitro experiments. Interestingly, although Wnt/TCF7L2 can promote the formation of SSCs, its function must be dependent on the expression of TDRD1, which was also repeatedly demonstrated as a target gene of the Wnt/TCF7L2 signaling pathway. Mechanistically, we found a large number of CpG sites in the TDRD1 promoter, and BSP analysis also confirmed that DNA methylation modifications in the TDRD1 promoter were significantly higher in embryonic stem cells than in SSCs, and further dual-luciferase reporter system assays revealed that low DNA methylation modification levels could enhance TDRD1 promoter activity; although previous studies demonstrated that TCF7L2 could enrich in the TDRD1 promoter region, the binding of the two was dependent on low DNA methylation modification. Taken together, we confirmed that low DNA methylation mediates Wnt/TCF7L2 regulation of TDRD1 to promote the formation of SSCs, providing a basis for SSCs in improving animal productivity.
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Could ultrasound midwifery training increase antenatal detection of congenital anomalies in Ghana? As part of World Health Organization (WHO) 2016 updated antenatal care (ANC) guidelines routine ultrasonography is recommended, including to detect congenital anomalies. The Ghana Health Service (GHS) developed an in-service midwifery ultrasound training course in 2017, which includes fetal anomaly detection. Training rollout has been very limited. We sought to determine proportions of anomalies among neonates presenting to Tamale Teaching Hospital (TTH) that should be prenatally detectable by course-trained midwives in order to determine training program potential utility.
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A systematic evaluation of the computational tools for ligand-receptor-based cell-cell interaction inference. Cell-cell interactions (CCIs) are essential for multicellular organisms to coordinate biological processes and functions. One classical type of CCI interaction is between secreted ligands and cell surface receptors, i.e. ligand-receptor (LR) interactions. With the recent development of single-cell technologies, a large amount of single-cell ribonucleic acid (RNA) sequencing (scRNA-Seq) data has become widely available. This data availability motivated the single-cell-resolution study of CCIs, particularly LR-based CCIs. Dozens of computational methods and tools have been developed to predict CCIs by identifying LR-based CCIs. Many of these tools have been theoretically reviewed. However, there is little study on current LR-based CCI prediction tools regarding their performance and running results on public scRNA-Seq datasets. In this work, to fill this gap, we tested and compared nine of the most recent computational tools for LR-based CCI prediction. We used 15 well-studied scRNA-Seq samples that correspond to approximately 100K single cells under different experimental conditions for testing and comparison. Besides briefing the methodology used in these nine tools, we summarized the similarities and differences of these tools in terms of both LR prediction and CCI inference between cell types. We provided insight into using these tools to make meaningful discoveries in understanding cell communications.
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The role of cytokeratin 19 levels in the determination of endometriosis stages. Endometrisosis, one of the most common gynecological disease, is characterized by the presence of endometriotic tissue outside of uterine cavity. The development and the validation of a simple blood biomarker specific and sensitive for endometriosis may facilitate the rapid and the accurate diagnosis of the disease and thus early treatment. Cytokeratin expression changes during epithelial differentiation and this expression is important for the modulation and the control of cell cycle regulation, tumor cell motility and apoptosis. Cytokeratin 19 (CK-19) is expressed in most simple epithelial cells and their malignant counterparts. The aim of this study is to investigate serum CK-19 expression levels in patients with endometriosis and to determine the diagnostic role of CK-19 levels in differentiating various stage of endometriosis.
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The relationship between ultraprocessed food consumption and obesity indicators in Iranian adults. Food processing changes the nature of foods, and it is growing globally due to its availability and affordability and its effects on the palatability of foods. Consumption of ultraprocessed foods (UPFs) may adversely affect weight gain. The purpose of the current study is to examine the association between UPFs consumption and adiposity among Iranian adults.
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Is the Revision Rate for Femoral Neck Fracture Lower for Total Hip Arthroplasty Than for Hemiarthroplasty?: A Comparison of Registry Data for Contemporary Surgical Options. When arthroplasty is indicated for a femoral neck fracture (FNF), it is unclear whether total hip arthroplasty (THA) or hemiarthroplasty (HA) is best. This study compares data from the Australian Orthopaedic Association National Joint Replacement Registry using contemporary surgical options.
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Molecular detection of Mycoplasma wenyonii and its closely related hemotropic Mycoplasma sp. in blood-sucking flies from a buffalo farm in Chachoengsao province, Thailand. Bovine hemoplasmosis is a disease in buffaloes and cattle caused by hemotropic mycoplasmas or hemoplasmas. Only two bovine hemoplasma species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been described in several countries. Hemoplasmas induce acute hemolytic anemia or chronic infection, leading to production loss. Bovine hemoplasma DNA was also detected in blood-sucking arthropods, suggesting vector transmission in farms. To date, no studies of the molecular detection of bovine hemoplasmas in Thai buffaloes and arthropod vectors have been reported. This study aimed to study the 1-year diversity of hematophagous flies in a buffalo farm located in Chachoengsao province, Thailand, and to investigate the molecular occurrence of bovine hemoplasmas in those flies using a polymerase chain reaction (PCR) assay and sequence analyses. A total of 1,488 mosquitoes, 867 stable flies, and 312 tabanid flies were collected during this study. The most abundant mosquitoes, stable flies, and tabanid flies were Culex tritaeniorhynchus, Stomoxys calcitrans, and Tabanus megalops, respectively. A total of 249 genomic DNA samples of flies were tested using a PCR assay based on the 16S rRNA gene; 23.69% (59/249) of the insect samples were positive in this assay. Positive samples (n = 8) were subjected to bidirectional sequencing. The BLAST results showed that only three samples from Stomoxys calcitrans and two samples from Tabanus megalops showed 99.90% and 99.17% similarities to the M. wenyonii isolate B003 (MG948626/Water buffalo/Cuba) and the M. wenyonii isolate C124 (MG948625/Cattle/Cuba), respectively. This molecular occurrence of bovine hemoplasmas in blood-sucking flies suggested that those flies are the mechanical vectors for bovine hemoplasmas in Thailand. Based on the phylogenetic analysis of the 16S rRNA gene, the sequences of M. wenyonii were likely classified into two subgroups (A and B), suggesting closely related bovine hemoplasma species. Finally, the genetic analysis of the 23S rRNA gene from these two subgroups revealed that subgroup A could be M. wenynoii and subgroup B may be a subspecies of M. wenyonii or another putative novel species. However, further investigation should be conducted in buffaloes, cattle, and blood-sucking flies to gain more 16S rRNA and 23 rRNA gene sequences of bovine hemoplasmas.
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Why Give My Surgical Patients Probiotics. Although there are various hypotheses on the health-promoting roles probiotic supplementation play-via targeting the gut microbiota and/or regulating the systemic immune and metabolic responses-the precise nature of this benefit in restitution of health following surgery remains under discussion and in doubt [...].
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Application and prospect of quasi-targeted metabolomics in age-related hearing loss. Age-related hearing loss (ARHL) is a common sensory deficit in the elderly, which seriously affects physical and mental health. Therefore, understanding its underlying molecular mechanisms and taking interventions to treat ARHL are urgently needed. In our study, cochlea of 4-week-old C57BL/6 mice as the Youth group (n = 6) and 48-week-old cochlea as the Old group (n = 6) were subjected to quasi-targeted metabolomics analysis by Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). In total, 208 differential metabolites were identified in 12 cochlea samples, which highlighted the following discriminant compounds: tryptophan, piperidine, methionine, L-arginine, histamine, serotonin, acetylcholine, and 4-aminobutyric acid. Differentially expressed metabolites were identified which were involved in KEGG pathways related to the digestion and absorption of oxidative stress associated amino acids, Synaptic vesicle cycle of serotonin, Pantothenate and CoA Biosynthesis. These findings are a first step toward elucidating the pathophysiological pathways involved in the etiology of ARHL and provide the possibility to further explore the mechanisms of ARHL using metabolomic analysis.
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Review article: obesity and colorectal cancer. Obesity is a growing global public health problem. More than half the European and North American population is overweight or obese. Colon and rectum cancers are still the second leading cause of cancer death worldwide, and epidemiological data support an association between obesity and colorectal cancers (CRCs).
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Cell-in-Cell: From Cell Biology to Translational Medicine. Cell-in-cell structures (CICs) refer to cytoplasmic internalization of a cell by another cell, which are found throughout various biological systems and have been a part of scientific dogma for a long time. However, neither the mechanisms underlying this phenomenon nor their possible roles in disease development have resulted in major breakthroughs until recent years. In view of the ubiquity of CICs in inflammatory tissue and tumors, it is tempting to think that these specific structures could be associated with clinical diagnosis and treatment and thus would become a new hotspot for translational medicine. Translational medicine is a new concept in the field of international biomedical research that appeared in the last 20 years, which transforms basic research into clinical application. With the growing interest in this field, this review addresses recent research on CICs and their potential clinical implications in cytomorphological diagnosis and the pathology of human diseases, while discussing as yet unanswered questions. We also put forward future directions to reduce the gap in our knowledge caused by our currently limited understanding of CICs.
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Phage Resistance Reduced the Pathogenicity of Xanthomonas oryzae pv. oryzae on Rice. Plants grow together with microbes that have both negative and positive impacts on the host, while prokaryotes are in turn also hosts for viruses, co-evolving together in a complex interrelationship. Most research focuses on the interaction of either bacterial pathogens interacting with the plant host, or the impact on viruses on their pathogenic bacterial hosts. Few studies have investigated the co-evolution of bacterial pathogens with their host plants as well as with their bacterial viruses. In this work, we aimed to identify the genes that were associated with both phage sensitivity and host pathogenicity of the bacterium Xanthomonas oryzae pv. oryzae (Xoo), which is the most important bacterial rice pathogen. Using the Tn5 transposon mutation technology, we created a library of Xoo strain C2 comprising 4524 mutants, which were subsequently tested for phage infectability. The phage infection tests showed that less than 1% of the mutants ( n = 36) were resistant to phage infection, which was attributed to the Tn5 insertion in 19 genes. Interestingly, three out of 19 genes that conveyed resistance to the phage resulted in reduced pathogenicity to rice seedlings compared to the wild type. We identified three genes involved in both phage infection and bacterial virulence, which were studied by knockout mutants and complementation experiments. All of the three knockout mutants were resistant to infection by phage X2, while the complemented strains restored the susceptibility to the bacterial virus. Surprisingly, the genes are also essential for pathogenicity, which we confirmed by single knockout mutants corresponding to the Tn5 mutants. All three genes are involved in lipopolysaccharide synthesis, thus changing the cell envelope surface molecule composition. Our work shows a possible balance in terms of the connection between bacterial virulence and phage resistance, supporting the deployment of phages for the biocontrol of plant pathogens.
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Lactobacillus plantarum ST-III modulates abnormal behavior and gut microbiota in a mouse model of autism spectrum disorder. Probiotic treatment might improve autism spectrum disorder (ASD) behavior. In this study, we investigated the improvement effects of Lactobacillus plantarum ST-III on a mouse model of ASD, which was constructed using triclosan. After two weeks of L. plantarum ST-III oral feeding, autism-like social deficits in male mouse models were ameliorated. L. plantarum ST-III also attenuated the self-grooming and freezing times of female mice. High-throughput sequencing revealed changes in the gut microbiota after L. plantarum ST-III intervention. In the female probiotic group, the abundance of beneficial Lachnospiraceae bacteria increased, whereas that of harmful Alistipes bacteria decreased. Correlation analysis showed that amelioration of abnormal behavior in a mouse model of ASD was related to the involvement of certain metabolic pathways. A reduction in the abundance of Alistipes was involved in stereotyped behavioral improvement. Thus, oral supplementation with L. plantarum ST-III can help improve social behavior in a male mouse model of ASD and contribute to more balanced intestinal homeostasis.
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Extraction and separation feasibility of cerium (III) and lanthanum (III) from aqueous solution using modified graphite adsorbent. Graphite (GR) and graphite/alginate (GRA) composite were synthesized utilizing the thermal annealing technique and used as a new adsorbent material for the selective separation and removal of La(III) and Ce(III) from aqueous solutions. Fourier transform infrared (FTIR) spectroscopy, thermal analysis (DTA, TGA), X-ray diffraction (XRD), surface area, porosity, and scanning electron microscope (SEM) were also used to characterize the generated material. Distinct experiments were performed to test the ability of the GRA to La(III) and Ce(III) removal, which include the effect of pH, shaken time, initial concentration of La(III), and Ce(III) at different temperatures range. After 20 min, both ions have reached equilibrium. The pseudo second-order kinetic model was chosen as one which best fits the experimental evidence and better reflects the chemical sorption process. Adsorption isotherm was studied using the Langmuir, Freundlich, and D-R models. The Langmuir model was used to better fit the results obtained. At 25 °C, Ce(III) and La(III) have maximum monolayer capacities of 200 and 83.3 mg/g, respectively. The sorption was endothermic reaction and spontaneous, as illustrated by the data of thermodynamics studies. GRA has the ability to be used as a novel lanthanide adsorbent material, especially for selective separation between Ce(III) and La(III).
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Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy. To evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.
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Utility of CD138/syndecan-1 immunohistochemistry for localization of plasmacytes is tissue-dependent in B6 mice. Inflammation is present in many diseases and identification of immune cell infiltration is a common assessment. CD138 (syndecan-1) is a recommended immunohistochemical marker for human plasmacytes although it is also expressed in various epithelia and tumors. Similarly, CD138 is a marker for murine plasmacytes, but its tissue immunostaining is not well-defined. Endogenous CD138 expression is an important confounding factor when evaluating plasmacyte infiltration. We studied two plasmacyte markers (CD138 and Kappa light chains) for endogenous immunostaining in five organs and one tumor from B6 mice.
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Is metformin a possible treatment for diabetic neuropathy? Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.
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