bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond apples and pears: sex-specific genetics of body fat percentage
Authors: Roshandel Delnaz , Lu Tianyuan , Paterson Andrew D. , Dash Satya 
Published: October 2023

IntroductionBiological sex influences both overall adiposity and fat distribution. Further, testosterone and sex hormone binding globulin (SHBG) influence adiposity and metabolic function, with differential effects of testosterone in men and women. Here, we aimed to perform sex-stratified genome-wide association studies (GWAS) of body fat percentage (BFPAdj) (adjusting for testosterone and sex hormone binding globulin (SHBG)) to increase statistical power.MethodsGWAS were performed in white British individuals from the UK Biobank (157,937 males and 154,337 females). To avoid collider bias, loci associated with SHBG or testosterone were excluded. We investigated association of BFPAdj loci with high density cholesterol (HDL), triglyceride (TG), type 2 diabetes (T2D), coronary artery disease (CAD), and MRI-derived abdominal subcutaneous adipose tissue (ASAT), visceral adipose tissue (VAT) and gluteofemoral adipose tissue (GFAT) using publicly available data from large GWAS. We also performed 2-sample Mendelian Randomization (MR) using identified BFPAdj variants as instruments to investigate causal effect of BFPAdj on HDL, TG, T2D and CAD in males and females separately.ResultsWe identified 195 and 174 loci explaining 3.35% and 2.60% of the variation in BFPAdj in males and females, respectively at genome-wide significance (GWS, p&lt;5x10-8). Although the direction of effect at these loci was generally concordant in males and females, only 38 loci were common to both sexes at GWS. Seven loci in males and ten loci in females have not been associated with any adiposity/cardiometabolic traits previously. BFPAdj loci generally did not associate with cardiometabolic traits; several had paradoxically beneficial cardiometabolic effects with favourable fat distribution. MR analyses did not find convincing supportive evidence that increased BFPAdj has deleterious cardiometabolic effects in either sex with highly significant heterogeneity.ConclusionsThere was limited genetic overlap between BFPAdj in males and females at GWS. BFPAdj loci generally did not have adverse cardiometabolic effects which may reflect the effects of favourable fat distribution and cardiometabolic risk modulation by testosterone and SHBG.
PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea
Authors: Díaz-García Elena , García-Sánchez Aldara , Alfaro Enrique , López-Fernández Cristina , Mañas Eva , Cano-Pumarega Irene , López-Collazo Eduardo , García-Río Francisco , Cubillos-Zapata Carolina 
Published: October 2023

IntroductionAlthough higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.MethodsThe expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models.ResultsData showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.DiscussionIn conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
Authors: Alsemeh Amira Ebrahim , Hulail Mohey A. E. , Mokhtar Hanan E. L. , Eldemerdash Reham Talaat , Banatean-Dunea Ioan , Fericean Liana Mihaela , Fathy Maha Abdelhamid , Arisha Ahmed Hamed , Khamis Tarek 
Published: October 2023

IntroductionOptic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.MethodsForty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.ResultsHistopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.ConclusionsBased on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.
Time-course adaptive changes in hippocampal transcriptome and synaptic function induced by simulated microgravity associated with cognition
Authors: Liang Rong , Wang Ling , Yang Qing , Xu Qing , Sun Shufan , Zhou Haichen , Zhao Meiling , Gao Jing , Zheng Chenguang , Yang Jiajia , Ming Dong 
Published: October 2023

IntroductionThe investigation of cognitive function in microgravity, both short-term and long-term, remains largely descriptive. And the underlying mechanisms of the changes over time remain unclear.MethodsBehavioral tests, electrophysiological recording, and RNA sequencing were used to observe differences in behavior, synaptic plasticity, and gene expression.ResultsInitially, we measured the performance of spatial cognition exposed to long-term simulated microgravity (SM). Both working memory and advanced cognitive abilities were enhanced. Somewhat surprisingly, the synaptic plasticity of the hippocampal CA3-CA1 synapse was impaired. To gain insight into the mechanism of changing regularity over time, transcriptome sequencing in the hippocampus was performed. The analysis identified 20 differentially expressed genes (DEGs) in the hippocampus after short-term modeling, 19 of which were up-regulated. Gene Ontology (GO) analysis showed that these up-regulated genes were mainly enriched in synaptic-related processes, such as Stxbp5l and Epha6. This might be related to the enhancement of working memory performance under short-term SM exposure. Under exposure to long-term SM, 7 DEGs were identified in the hippocampus, all of which were up-regulated and related to oxidative stress and metabolism, such as Depp1 and Lrg1. Compensatory effects occurred with increased modeling time.DiscussionTo sum up, our current research indicates that the cognitive function under SM exposure is consistently maintained or potentially even being enhanced over both short and long durations. The underlying mechanisms are intricate and potentially linked to the differential expression of hippocampal-associated genes and alterations in synaptic function, with these effects being time-dependent. The present study will lay the experimental and theoretical foundation of the multi-level mechanism of cognitive function under space flight.
Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing
Authors: Holubekova Veronika , Loderer Dusan , Grendar Marian , Mikolajcik Peter , Kolkova Zuzana , Turyova Eva , Kudelova Eva , Kalman Michal , Marcinek Juraj , Miklusica Juraj , Laca Ludovit , Lasabova Zora 
Published: October 2023

IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as driver mutations, gene methylations, etc., and influenced by tumor microenvironment (TME) pervaded with immune cells with both pro- and anti-tumor effects. The studying of interactions between the immune system (IS) and the TME is important for developing effective immunotherapeutic strategies for CRC. In our study, we focused on the analysis of expression profiles of inflammatory and immune-relevant genes to identify aberrant signaling pathways included in carcinogenesis, metastatic potential of tumors, and association of Kirsten rat sarcoma virus (KRAS) gene mutation.MethodsA total of 91 patients were enrolled in the study. Using NGS, differential gene expression analysis of 11 tumor samples and 11 matching non-tumor controls was carried out by applying a targeted RNA panel for inflammation and immunity genes containing 475 target genes. The obtained data were evaluated by the CLC Genomics Workbench and R library. The significantly differentially expressed genes (DEGs) were analyzed in Reactome GSA software, and some selected DEGs were used for real-time PCR validation.ResultsAfter prioritization, the most significant differences in gene expression were shown by the genes TNFRSF4, IRF7, IL6R, NR3CI, EIF2AK2, MIF, CCL5, TNFSF10, CCL20, CXCL11, RIPK2, and BLNK. Validation analyses on 91 samples showed a correlation between RNA-seq data and qPCR for TNFSF10, RIPK2, and BLNK gene expression. The top differently regulated signaling pathways between the studied groups (cancer vs. control, metastatic vs. primary CRC and KRAS positive and negative CRC) belong to immune system, signal transduction, disease, gene expression, DNA repair, and programmed cell death.ConclusionAnalyzed data suggest the changes at more levels of CRC carcinogenesis, including surface receptors of epithelial or immune cells, its signal transduction pathways, programmed cell death modifications, alterations in DNA repair machinery, and cell cycle control leading to uncontrolled proliferation. This study indicates only basic molecular pathways that enabled the formation of metastatic cancer stem cells and may contribute to clarifying the function of the IS in the TME of CRC. A precise identification of signaling pathways responsible for CRC may help in the selection of personalized pharmacological treatment.
A plasma miRNA-based classifier for small cell lung cancer diagnosis
Authors: Saviana Michela , Romano Giulia , McElroy Joseph , Nigita Giovanni , Distefano Rosario , Toft Robin , Calore Federica , Le Patricia , Morales Daniel Del Valle , Atmajoana Sarah , Deppen Stephen , Wang Kai , Lee L. James , Acunzo Mario , Nana-Sinkam Patrick 
Published: October 2023

IntroductionSmall cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based classifier to assist in SCLC diagnoses.MethodsWe profiled deregulated circulating cell-free miRNAs in the plasma of SCLC patients. We tested selected miRNAs on a training cohort and created a classifier by integrating miRNA expression and patients’ clinical data. Finally, we applied the classifier on a validation dataset.ResultsWe determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group.DiscussionThis study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies
Authors: Xie Hailun , Wei Lishuang , Liu Mingxiang , Liang Yanren , Wang Qiwen , Tang Shuangyi , Gan Jialiang 
Published: October 2023

BackgroundCombining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated.MethodsWe used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals.ResultsPatients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis.ConclusionOur findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.
Chinese cross-cultural adaptation and validation of the Well-being Numerical Rating Scales
Authors: Luo Qing , Liu Chunqin , Zhou Ying , Zou Xiaofang , Song Liqin , Wang Zihan , Feng Xue , Tan Wenying , Chen Jiani , Smith Graeme D. , Chiesi Francesca 
Published: October 2023

IntroductionWell-being is a multi-domain concept that involves measuring physical, psychological, social, and spiritual domains. However, there are currently few multi-domain and comprehensive well-being instruments available. In addition, measures that do exist customarily contain a vast number of items that may lead to boredom or fatigue in participants. The Well-being Numerical Rating Scales (WB-NRSs) offer a concise, multi-domain well-being scale. This study aimed to perform the translation, adaptation, and validation of the Chinese version of WB-NRSs (WBNRSs-CV).MethodsA total of 639 clinical participants and 542 community participants completed the WB-NRSs-CV, the Single-item Self-report Subjective Well-being Scale (SISRSWBS), the World Health Organization Five-item Well-Being Index (WHO-5), the 10-item Perceived Stress Scale (PSS-10), and the Kessler Psychological Distress Scale (K10).ResultsHigh internal consistency and test-retest reliability were obtained for both samples. Additionally, WB-NRSs-CV was positively associated with SISRSWBS and WHO-5 and negatively associated with PSS-10 and K10. In the item response theory analysis, the model fit was adequate with the discrimination parameters ranging from 2.73 to 3.56. The diffculty parameters ranged from −3.40 to 1.71 and were evenly spaced along the trait, attesting to the appropriateness of the response categories. The invariance tests demonstrated that there was no difference in WB-NRSs-CV across groups by gender or age.DiscussionThe WB-NRSs-CV was translated appropriately and cross-culturally adapted in China. It can be used as a rapid and relevant instrument to assess well-being in both clinical and non-clinical settings, with its utility for well-being measurement and management among the Chinese people.
Susceptibility and severity of COVID-19 and risk of psychiatric disorders in European populations: a Mendelian randomization study
Authors: Xue Hua , Zeng Li , Liu Shuangjuan 
Published: October 2023

BackgroundObservational studies have suggested that COVID-19 increases the prevalence of psychiatric disorders, but the results of such studies are inconsistent. This study aims to investigate the association between COVID-19 and the risk of psychiatric disorders using Mendelian randomization (MR) analysis.MethodsWe used summary statistics from COVID-19 Host Genetics Initiative genome-wide association study (GWAS) of COVID-19 involving 2,586,691 participants from European ancestry. Genetic variations of five psychiatric disorders including autism spectrum disorder (ASD) (N = 46,351), bipolar disorder (BID) (N = 51,710), major depressive disorder (MDD) (N = 480,359), anxiety disorder (N = 83,566), and schizophrenia (SCZ) (N = 77,096) were extracted from several GWAS of European ancestry. The inverse-variance weighted (IVW) method as the main MR analysis conducted. We further performed sensitivity analyzes and heterogeneity analyzes as validation of primary MR results.ResultsThe IVW analysis found that COVID-19 hospitalization phenotype was the risk factor for BID (OR = 1.320, 95% CI = 1.106–1.576, p = 0.002) and SCZ (OR = 1.096, 95% CI = 1.031–1.164, p = 0.002). Moreover, we detected a significant positive genetic correlation between COVID-19 severity and two psychiatric traits, BID (OR = 1.139, 95% CI = 1.033–1.256, p = 0.008) and SCZ (OR = 1.043, 95% CI = 1.005–1.082, p = 0.024). There was no evidence supporting the causal relationship between COVID-19 susceptibility and psychiatric disorders.ConclusionOur results found that the COVID-19 hospitalization phenotype and COVID-19 severity phenotype might be the potential risks of BID and SCZ in European populations. Therefore, patients infected with SARS-CoV-2 should have enhanced monitoring of their mental status.
What helps hospital staff in times of crisis: qualitative results of a survey on psychosocial resources and stressors in German hospitals during the COVID-19 pandemic
Authors: Schmidt-Stiedenroth Kira , Guthardt Lisa , Genrich Melanie , Köhne Mara , Stiawa Maja , Erschens Rebecca , Junne Florian , Maatouk Imad ,   The SEEGEN-Consortium, Gündel Harald , Angerer Peter , Müller Andreas 
Published: October 2023

BackgroundEven before the COVID-19 pandemic, hospital workers faced a tremendous workload. The pandemic led to different and additional strain that negatively affected the well-being of employees. This study aims to explore psychosocial resources and strategies that were used by hospital staff.MethodsIn the context of an intervention study, employees of three German hospitals were questioned in writing in summer and fall 2020. Five open-ended questions about the pandemic were asked to capture corresponding effects on daily work routine. Answers of 303 participants were evaluated using structuring qualitative content analysis.ResultsSignificant stressors and resources were identified in the areas of work content and task, social relations at work, organization of work, work environment and individual aspects. Stressors included, for example, emotional demands, conflicts, an increased workload, time and performance pressure. Important resources mentioned were, among others, the exchange with colleagues and mutual support. Sound information exchange, clear processes and guidelines and a positive work atmosphere were also important. In addition, the private environment and a positive mindset were perceived as helpful.ConclusionThis study contributes to a differentiated understanding of existing psychosocial resources of hospital staff in times of crisis. Identifying and strengthening these resources could reduce stress and improve well-being, making hospital staff better prepared for both normal operations and further crisis situations.
Characterization of the RAD52 Gene in the Budding Yeast Naumovozyma castellii
Authors: Itriago Humberto , Marufee Islam Zubaida , Cohn Marita 
Published: October 2023

Several sources of DNA damage compromise the integrity and stability of the genome of every organism. Specifically, DNA double-strand breaks (DSBs) can have lethal consequences for the cell. To repair this type of DNA damage, the cells employ homology-directed repair pathways or non-homologous end joining. Homology-directed repair requires the activity of the RAD52 epistasis group of genes. Rad52 is the main recombination protein in the budding yeast Saccharomyces cerevisiae, and rad52Δ mutants have been characterized to show severe defects in DSB repair and other recombination events. Here, we identified the RAD52 gene in the budding yeast Naumovozyma castellii. Our analysis showed that the primary amino acid sequence of N. castellii Rad52 shared 70% similarity with S. cerevisiae Rad52. To characterize the gene function, we developed rad52Δ mutant strains by targeted gene replacement transformation. We found that N. castellii rad52Δ mutants showed lowered growth capacity, a moderately altered cell morphology and increased sensitivity to genotoxic agents. The decreased viability of the N. castellii rad52Δ mutants in the presence of genotoxic agents indicates that the role of the Rad52 protein in the repair of DNA damage is conserved in this species.