Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of associations between MMP9 gene polymorphisms and breast cancer: Evidence from a meta-analysis

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which play critical roles in cancer progression and metastasis. In recent years, many researchers have been studying the relationship between MMP9 and breast cancer. However, it still remains indecisive. Therefore, we conducted a meta-analysis to draw more accurate conclusions. A total of 21 relevant documents were retrieved, including 25 case-control studies. We quantitatively analyzed the data obtained. To clarify the relationship between MMP9 polymorphism and breast cancer susceptibility under different conditions, we also made a further subgroup analysis for each locus. In summary, we discovered that MMP9 rs3918242 rendered an increased risk for breast cancer, especially among Iranians and Indians. MMP9 rs3787268 could be a protective factor. MMP9 rs17576 and MMP9 rs2250889 have no association with breast cancer risk.
Formation of molecular transistor electrodes by electromigration

In this work we obtained the gaps less than 5 nm wide in the thin (15 nm) gold films. These gaps can be used for the creation of the room-temperature single-electron transistor. We demonstrated the need of deposition of Au without an adhesive layer and elaborated the technique of the creation of thin (15 nm) and narrow (200 nm) gold electrodes on Al2O3. It provides a sufficient adhesion of Au film even without a buffer layer and subsequent successive gap implementation.
Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials

ABSTRACT Objectives This systematic review aimed to evaluate the efficacy of B vitamins and vitamin D therapy in improving the standard treatment of depression and anxiety disorders. We also aimed to gather the evidence supporting the recommendations for supplementation in clinical practice. Methods Performed between March 2020 and September 2021, the main inclusion criteria were randomized controlled trials (RCTs), with patients ≥ 18 years old, both sexes, fulfilling target diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), or mild to severe depressive and anxiety symptoms. In addition, the RCTs were included if the scales to assess the severity of the symptoms were standardized rating scales in psychiatric. Trials that reported diagnoses of schizophrenia, perinatal depression, bipolar depression, sleep disorders, eating disorders, cancer, and multiple sclerosis in association with any of the mentioned diagnoses were excluded. Results We identified 20 RCTs that matched all eligibility criteria, totaling 2,256 subjects, diagnosed with MDD, GAD, and depressive or anxiety symptoms. Supplementation with folic acid or L-methylfolate, B1, B12 or methylcobalamin, and vitamin D (in different doses and study duration) significantly decreased depression score scales by increasing response to standard pharmacological treatment or as monotherapy, including partial or complete remission. As for anxiety symptoms, the availability of results is limited to adjuvant vitamin D therapy. Discussion B vitamins and vitamin D associated with other compounds also showed significant results, so the improvement in symptoms cannot be attributed strictly to those. Our results suggest that intervention with B vitamins and/or vitamin D may be an effective and well-tolerated adjuvant strategy for improving the symptoms of depression and anxiety, according to the patient’s clinical status and nutritional biomarkers.
High rate of muscle injury despite no changes in physical, physiological and psychophysiological parameters in a professional football team during a long-congested fixture period

ABSTRACT This study aimed to analyse match availability, participation, and muscle injury incidence and to compare the effect of time intervals between matches (3–4 versus 6–7 days) on physical, physiological, and psychophysiological parameters in a professional football team during a prolonged congested fixture period. Thirteen professional male football players (29.2 ± 4.8 years old; 78.5 ± 8.3 kg; 179.3 ± 8.8 cm;) participated. Data were collected during 17 consecutive weeks for 35 official matches separated by an average interval of ≤ 3.5 days. Results showed a player availability of 84.8 ± 16.1% while match participation was 68.8% ± 6.4%. Muscle injury incidence was 19.0/ 1,000 hours of match exposure. These injuries occurred after individual players participated in sequences of 8.3 ± 3.3 consecutive matches with intervals of 3.8 ± 0.8 days. No differences were observed in physical performance or in fatigue-related parameters irrespective of the time interval between matches. A high player availability rate was observed. No differences were observed in physical, physiological, and psychophysiological indices of performance when comparing shorter and longer time intervals between consecutive matches.Prolonged exposure to fixture congestion resulted in an high risk of incurring muscle injury.
Sexual dimorphism: increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats

Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1‐13C]‐acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT‐qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low‐density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).
PABP prevents the untimely decay of select mRNA populations in human cells

Gene expression is tightly regulated at the levels of both mRNA translation and stability. The poly(A)‐binding protein (PABP) is thought to play a role in regulating these processes by binding the mRNA 3′ poly(A) tail and interacting with both the translation and mRNA deadenylation machineries. In this study, we directly investigate the impact of PABP on translation and stability of endogenous mRNAs in human cells. Remarkably, our transcriptome‐wide analysis only detects marginal mRNA translation changes in PABP‐depleted cells. In contrast, rapidly depleting PABP alters mRNA abundance and stability, albeit non‐uniformly. Otherwise stable transcripts, including those encoding proteins with constitutive functions, are destabilized in PABP‐depleted cells. In contrast, many unstable mRNAs, including those encoding proteins with regulatory functions, decay at similar rates in presence or absence of PABP. Moreover, PABP depletion‐induced cell death can partially be suppressed by disrupting the mRNA decapping and 5′–3′ decay machinery. Finally, we provide evidence that the LSM1‐7 complex promotes decay of “stable” mRNAs in PABP‐depleted cells. Taken together, these findings suggest that PABP plays an important role in preventing the untimely decay of select mRNA populations.
A systemic review and meta-analysis on the efficacy and safety of ferumoxytol for anemia in chronic kidney disease patients

Abstract Purpose To evaluate the efficacy of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and adverse event incidence in chronic kidney disease patients. Methods We performed a systematic search of six academic databases (EMBASE, CENTRAL, Scopus, PubMed, Web of sciences, and MEDLINE), adhering to PRISMA guidelines. We performed a meta-analysis on relevant studies to evaluate the overall influence of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and treatment related treatment emergent adverse events (TEAEs) incidence in chronic kidney disease patients. Results Seven eligible studies were identified from a total of 1397 studies. These studies contained data on 3315 participants with chronic kidney disease (mean age: 59.2 ± 4.6 years). A meta-analysis revealed that ferumoxytol administration had positive effects on hemoglobin levels (Hedge’s g statistic: 0.51) and ferritin level (0.88), transferrin saturation (0.39). Besides, we also report reduced incidence of treatment related TEAEs (−0.24) for patients consuming ferumoxytol as compared conventional iron supplement formulations. Conclusions This meta-analysis provides preliminary evidence that ferumoxytol use exerts beneficial effects on the overall hematological outcomes in patients with chronic kidney disease. This study also reports improved treatment related safety profile for ferumoxytol when compared with conventional iron formulations. The findings from this study can have direct implications in forming best practice guidelines for managing anemia in patients with chronic kidney disease.
Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis.

BACKGROUND many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. OBJECTIVES this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. METHODS this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. RESULTS subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. CONCLUSION The TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.
IL13Pred: A method for predicting immunoregulatory cytokine IL-13 inducing peptides for managing COVID-19 severity

Interleukin 13 (IL-13) is an immunoregulatory cytokine that is primarily released by activated T-helper 2 cells. It induces the pathogenesis of many allergic diseases, such as airway hyperresponsiveness, glycoprotein hypersecretion and goblet cell hyperplasia. IL-13 also inhibits tumor immunosurveillance, which leads to carcinogenesis. In recent studies, elevated IL-13 serum levels have been shown in severe COVID-19 patients. Thus it is important to predict IL-13 inducing peptides or regions in a protein for designing safe protein therapeutics particularly immunotherapeutic. This paper describes a method developed for predicting, designing and scanning IL-13 inducing peptides. The dataset used in this study contain experimentally validated 313 IL-13 inducing peptides and 2908 non-inducing homo-sapiens peptides extracted from the immune epitope database (IEDB). We have extracted 95 key features using SVC-L1 technique from the originally generated 9165 features using Pfeature. Further, these key features were ranked based on their prediction ability, and top 10 features were used for building machine learning prediction models. In this study, we have deployed various machine learning techniques to develop models for predicting IL-13 inducing peptides. These models were trained, test and evaluated using five-fold cross-validation techniques; best model were evaluated on independent dataset. Our best model based on XGBoost achieves a maximum AUC of 0.83 and 0.80 on the training and independent dataset, respectively. Our analysis indicate that certain SARS-COV2 variants are more prone to induce IL-13 in COVID-19 patients. A standalone package as well as a web server named ‘IL-13Pred’ has been developed for predicting IL-13 inducing peptides (https://webs.iiitd.edu.in/raghava/il13pred/). Key Points Interleukin-13, an immunoregulatory cytokine plays an important role in increasing severity of COVID-19 and other diseases. IL-13Pred is a highly accurate in-silico method developed for predicting the IL-13 inducing peptides/ epitopes. IL-13 inducing peptides are reported in various SARS-CoV2 strains/variants proteins. This method can be used to detect IL-13 inducing peptides in vaccine candidates. User friendly web server and standalone software is freely available for IL-13Pred Author’s Biography Shipra Jain is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. Anjali Dhall is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. Sumeet Patiyal is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Correlates of psychological distress among adults with obesity during the COVID-19 pandemic

Abstract Objective The present study evaluated changes in stress and loneliness among participants with obesity engaged in weight loss self-management in the United States (US) during COVID-19, and identified factors that may increase risk or protect against psychosocial distress during this time. Design Participants who were enrolled in a weight self-management program prior to the COVID-19 pandemic (N = 55, 91% female, 36% Caucasian, mean age = 49.8 years) completed an online survey about social, economic and health behaviour changes during COVID-19 and their relationship to changes in perceived stress and loneliness. Main outcome measures Perceived Stress (PSS-4), Loneliness (PROMIS loneliness and social isolation questionnaire). Results Compared to pre-COVID assessments, stress and loneliness increased 40% two months into the COVID-19 pandemic-related shutdown. Higher body mass index (BMI) and social distancing were associated with increases in both loneliness and stress. Alcohol intake was associated with increased stress, and working from home was associated with increased loneliness. Conclusion Individuals with obesity endorsed increased stress and loneliness during COVID-19, which may be exacerbated among those with a higher BMI and greater adherence to social distancing guidelines. Ongoing attention to psychosocial well-being among individuals with obesity will remain imperative both during the ongoing pandemic and beyond.
Distinct microbiota composition and fermentation products indicate functional compartmentalization in the hindgut of a marine herbivorous fish

Many marine herbivorous fishes harbour diverse microbial communities in the hindgut that can play important roles in host health and nutrition. Kyphosus sydneyanus is a temperate marine herbivorous fish that feeds predominantly on brown seaweeds. We employed 16S rRNA gene amplicon sequencing and gas chromatography to characterize microbial communities and their metabolites in different hindgut regions of six K. sydneyanus. Measurements were confined to three distal sections of the intestine, labelled III, IV and V from anterior to posterior. A total of 625 operational taxonomic units from 20 phyla and 123 genera were obtained. Bacteroidota, Firmicutes and Proteobacteria were the major phyla in mean relative abundance, which varied along the gut. Firmicutes (76%) was the most dominant group in section III, whereas Bacteroidota (69.3%) dominated section V. Total short‐chain fatty acid (SCFA) concentration was highest in sections IV and V, confirming active fermentation in these two most distal sections. The abundance of Bacteroidota correlated with propionate concentration in section V, while Firmicutes positively correlated with formate in sections III and IV. Acetate levels were highest in sections IV and V, which correlated with abundance of Bacteroidota. Despite differences in gut microbial community composition, SCFA profiles were consistent between individual fish in the different hindgut regions of K. sydneyanus, although proportions of SCFAs differed among gut sections. These findings demonstrate functional compartmentalization of the hindgut microbial community, highlighting the need for regional sampling when interpreting overall microbiome function. These results support previous work suggesting that hindgut microbiota in marine herbivorous fish are important to nutrition in some host species by converting dietary carbohydrates into metabolically useful SCFAs.
Molecular dynamics simulations reveal the activation mechanism of mutations G12V and Q61L of Cdc42

Cell division control protein 42 homolog (Cdc42), which contributes to multiple cellular processes including cell proliferation and migration, is a potential target for cancer therapy, especially in the intervention of tumor migration. Cdc42's mutants G12V and Q61L are discovered constitutively active, and the overexpression of them exhibits oncogenic activities. Here, using molecular dynamics (MD) simulations and dynamic analysis, we illustrated the activation mechanism of Cdc42G12V and Cdc42Q61L. Without GAP, the two mutations differently elicited state transition from the wild‐type's open “inactive” state 1 to the closed “active” state 2, induced by the introduction of a newly formed water‐mediated T35‐γ‐phosphate hydrogen bond in G12V system and the additional hydrophobic interactions between L61 and T35 together with the direct T35‐γ‐phosphate hydrogen bond in Q61L system. When binding with GAP, both mutations weakened the hydrogen bond interactions between Cdc42‐GTP and GAP's finger loop, and disturbed the catalytically competent organizations of GAP's catalytic R305/R306 and Cdc42's Q61, thereby impairing the GAP‐mediated GTP hydrolysis. Our findings first reveal the activation mechanism of Cdc42's G12V and Q61L mutants on a molecular basis, which provide new insights into the structural and dynamical characteristics of Cdc42 and its mutants and can be exploited in the further development of novel therapies targeting Cdc42‐related cancers.
Immobilized enzyme for screening and identification of anti-diabetic components from natural products by ligand fishing

Abstract Diabetes is a chronic metabolic disease caused by insufficient insulin secretion and insulin resistance. Natural product is one of the most important resources for anti-diabetic drug. However, due to the extremely complex composition, this research is facing great challenges. After the advent of ligand fishing technology based on enzyme immobilization, the efficiency of screening anti-diabetic components has been greatly improved. In order to provide critical knowledge for future research in this field, the application progress of immobilized enzyme in screening anti-diabetic components from complex natural extracts in recent years was reviewed comprehensively, including novel preparation technologies and strategies of immobilized enzyme and its outstanding application prospect in many aspects. The basic principles and preparation steps of immobilized enzyme were briefly described, including entrapment, physical adsorption, covalent binding, affinity immobilization, multienzyme system and carrier-free immobilization. New formatted immobilized enzymes with different carriers, hollow fibers, magnetic materials, microreactors, metal organic frameworks, etc., were widely used to screen anti-diabetic compositions from various natural products, such as Ginkgo biloba, Morus alba, lotus leaves, Pueraria lobata, Prunella vulgaris, and Magnolia cortex. Furthermore, the challenges and future prospects in this field were put forward in this review.
Tumours modulate the systemic vascular response to anti‐angiogenic therapy

Toxicologic evaluation of new drug candidates routinely utilizes healthy animals. In oncology, there remains a limited understanding of the effects of novel test candidates in a diseased host. For vascular modulating agents (VMAs), an increased understanding of preclinical tumour–host interaction, and its potential to exacerbate or alleviate ‘off‐target’ effects of anti‐angiogenic administration, could aid in the prediction of adverse clinical outcomes in a defined cancer patient. We have previously reported that the implantation and growth of a range of human‐ and mouse‐derived tumours leads to structural vascular and, potentially, functional signalling changes within host mouse endocrine tissues, indicating possible roles for tumour‐ and host‐derived cytokines/growth factors and the liberation of myeloid‐derived suppressor cells in this phenomenon. Here, we further demonstrate that the growth of the Calu‐6 xenograft is associated with a resistance to VMA‐induced mouse peripheral endocrine vascular rarefaction (toxicity), with potential functional impact, notably with respect to mixed tyrosine kinase inhibition. The pathogenesis of these findings indicates a potential role for both tumour‐ and host‐derived basic fibroblast growth factor (bFGF), with associated upregulation in the intra‐tumoural autotaxin‐lysophosphatic acid signalling axis.