bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady-state memory-phenotype conventional CD4+ T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis
Authors: Cho Min-Ji , Lee Hong-Gyun , Yoon Jae-Won , Kim Gil-Ran , Koo Ja-Hyun , Taneja Reshma , Edelson Brian T. , Lee You Jeong , Choi Je-Min 
Published: May 2023

AbstractMemory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1β without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1β signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.
Integrative multi-omics and drug–response characterization of patient-derived prostate cancer primary cells
Authors: Wang Ziruoyu , Li Yanan , Zhao Wensi , Jiang Shuai , Huang Yuqi , Hou Jun , Zhang Xuelu , Zhai Zhaoyu , Yang Chen , Wang Jiaqi , Zhu Jiying , Pan Jianbo , Jiang Wei , Li Zengxia , Ye Mingliang , Tan Minjia , Jiang Haowen , Dang Yongjun 
Published: May 2023

AbstractProstate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies.
Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study
Authors: Zou Hede , Zhang Xuesong , Chen Wenkang , Tao Yi , Li Bolin , Liu Hanfei , Wang Ruikun , Zhao Jiayou 
Published: May 2023

AbstractVascular endothelial is considered to be a key factor in the pathogenesis of erectile dysfunction (ED). The purpose is to reveal the research trend of the field of ED and vascular endothelium. In addition, the goal is to discover the role and mechanism of vascular endothelium in ED. Bibliometrics and visualization methods based on CiteSpace were selected. We conducted the co-authorship analysis of countries, institutions and authors, co-occurrence analysis of keywords, and co-citation analysis of literature and authors through CiteSpace 6.1.R3. 1431 articles from Web of Science Core Collection (WOSCC) were included in the analysis from 1991 to 2022. We found some influential and cutting-edge nodes in each map, including countries, institutions, authors, articles, etc. Stem cell, therapy, oxidative stress, cavernous nerve injury, radical prostatectomy, fibrosis, erectile function, mesenchymal stem cell, and apoptosis may be hot keywords. In conclusion, the efficacy and mechanisms of stem cells and their derivatives in the treatment of diabetes (DM) ED and cavernous nerve injury (CNI) ED are the future research trends. Stem cells therapy for ED is a hot spot in this field, which side notes that stem cells may work mainly through improving endothelial function. Vascular endothelial cells and VEGF may repair nerve and cavernous smooth muscle directly or indirectly, and finally polish up erectile function.
Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids
Authors: Papsdorf Katharina , Miklas Jason W. , Hosseini Amir , Cabruja Matias , Morrow Christopher S. , Savini Marzia , Yu Yong , Silva-García Carlos G. , Haseley Nicole R. , Murphy Luke Meraz , Yao Pallas , de Launoit Elisa , Dixon Scott J. , Snyder Michael P. , Wang Meng C. , Mair William B. , Brunet Anne 
Published: May 2023

AbstractDietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans. MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids—a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging.
Positive correlation between wet-day frequency and intensity linked to universal precipitation drivers
Authors: McErlich Cameron , McDonald Adrian , Schuddeboom Alex , Vishwanathan Gokul , Renwick James , Rana Sapna 
Published: May 2023

AbstractUnderstanding precipitation is essential for quantifying weather and climate-related risks. Changes in precipitation climatology are typically based on independent analysis of precipitation frequency and intensity. Here we show that where it rains more often, it also rains harder. When grouping global precipitation reanalysis data and observations from the past 40 years into regions of similar wet-day frequency, regardless of geographical separation, there is a strong correlation with wet-day intensity distributions. These wet-day-frequency regions are also more physically coherent than regions based on geographical location. We find the coherent relationship between wet-day frequency and intensity distributions is partially explained by wet-day-frequency regions having similar vertical velocity and convective available potential energy distributions, once polar regions are excluded. These represent dynamic and thermodynamic processes that indicate how conducive wet-day-frequency regions are to large-scale and convective precipitation. This suggests that the main drivers of precipitation are universal. We also show that extreme-precipitation metrics are dependent on wet-day frequency within our framework. Our results imply that wet-day frequency could be used to derive estimates of extreme-precipitation climate indices and corresponding uncertainties, these uncertainties being related to local processes.
Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits
Authors: Zhang Brian C. , Biddanda Arjun , Gunnarsson Árni Freyr , Cooper Fergus , Palamara Pier Francesco 
Published: May 2023

AbstractGenome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N = 134, frequency range 0.0007−0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N = 64). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r = 0.72) underlying sequencing variants enriched (4.8×) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.
Dynamic epistasis analysis reveals how chromatin remodeling regulates transcriptional bursting
Authors: Brouwer Ineke , Kerklingh Emma , van Leeuwen Fred , Lenstra Tineke L. 
Published: May 2023

AbstractTranscriptional bursting has been linked to the stochastic positioning of nucleosomes. However, how bursting is regulated by the remodeling of promoter nucleosomes is unknown. Here, we use single-molecule live-cell imaging of GAL10 transcription in Saccharomyces cerevisiae to measure how bursting changes upon combined perturbations of chromatin remodelers, the transcription factor Gal4 and preinitiation complex components. Using dynamic epistasis analysis, we reveal how the remodeling of different nucleosomes regulates transcriptional bursting parameters. At the nucleosome covering the Gal4 binding sites, RSC and Gal4 binding synergistically facilitate each burst. Conversely, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. At canonical TATA boxes, the nucleosomes are displaced by TBP binding to allow for transcription activation even in the absence of remodelers. Overall, our results reveal how promoter nucleosome remodeling together with Gal4 and preinitiation complex binding regulates transcriptional bursting.
Personality traits and dimensions of mental health
Authors: Kang Weixi , Steffens Francois , Pineda Sònia , Widuch Kaya , Malvaso Antonio 
Published: May 2023

AbstractIndividuals are different in a relatively constant pattern of thoughts, feeling, and behaviors, which are called personality traits. Mental health is a condition of well-being in which people may reach their full potential and deal effectively with stress, work efficiently, and contribute to their communities. Indeed, the link between personality and mental health as indicated by the 12-item version of the general health questionnaires (GHQ-12) has been well-established according to evidence found by decades of research. However, the GHQ-12 comprises many questions asking about different dimensions of mental health. It is unclear how personality traits relate to these dimensions of mental health. In this paper, we try to address this question. We analyzed data from 12,007 participants from the British Household Panel Study (BHPS) using a confirmatory factor analysis (CFA) and generalized linear models. We replicated the factor structure of GHQ-12 labeled as GHQ-12A (social dysfunction & anhedonia; 6 items), GHQ-12B (depression & anxiety; 4 items), and GHQ-12C (loss of confidence; 2 items). Moreover, Neuroticism was positively related to all dimensions of mental health issues, Extraversion was negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12B (depression & anxiety), Agreeableness and Conscientiousness were negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12C (loss of confidence), and Openness was negatively related to GHQ-12B (depression & anxiety). These results contribute to theories including the predisposition/vulnerability model, complication/scar model, pathoplasty/exacerbation model, and the spectrum model, which propose that personality traits are linked to mental health and explained possible reasons. Psychologists may use results from this study to identify individuals who may be at high risk of developing various non-psychiatric mental health issues and intervene to avoid negative outcomes.
Uropathogenic bacterial profile and antibiotic susceptibility pattern of isolates among gynecological cases admitted to Jimma Medical Center, South West Ethiopia
Authors: Teferi Sisay , Sahlemariam Zewdineh , Mekonnen Mekidim , Tamrat Rahel , Bekana Teshome , Adisu Yonas , Darge Tefera 
Published: May 2023

AbstractUrinary tract infection (UTI) is one of the most common bacterial infections in women; about 50% of women get during their life time. Moreover, it is a common health problem in patients with gynecological pathologies, which increases the chance of acquiring infection. The aim of this study was to determine the bacterial profile that causes UTI and their antibiotic susceptibility pattern among admitted gynecological cases. A cross-sectional study was conducted in south west Ethiopia region. A total of 386 patients admitted with gynecological cases were recruited by sequential sampling technique and structured questionnaire was used to collect socio-demographic and risk factor-related data. About 10 ml freshly voided midstream and catheterized urine specimens were collected using sterile containers. Identification of isolate was done using culture characteristics, gram staining, and a series of biochemical tests. The antibiotic susceptibility test was performed as per the Kirby–Bauer disc diffusion technique. The data obtained were entered into EpiData Version 3.1 and analyzed using SPSS Version 25. A P value of less than 0.05 was used as a level of significance. In this study, the overall prevalence of UTI was 25.4%. Escherichia coli was the most frequently isolated bacteria, which accounted for 38 (37.6%), followed by Klebsiella species 22 (21.8%), CONS 14 (13.9%), Staphylococcus aureus 10 (9.9%), Enterobacter species 6 (5.9%), Citrobacter species 5 (4.9%), Proteus mirabilis 4 (4%), and Pseudomonas aeroginosa 2(2%). Histories of UTI (AOR = 1.977, 95% CI 1.06, 3.68, P = 0.032) and catheterization (AOR = 2.38, 95% CI 1.28, 4.45, P = 0.006) were found to be statistically associated with significant bacteriuria. Gram-negative isolates showed a high level of resistance, 88.3% for ampicillin and 66.2% for tetracycline, and a relatively low level of resistance against ceftazidime, 22.1%, and meropenem, 3.9%. Gram-positive uropathogens showed a high level of resistance to penicillin, 91.6%, whereas all isolates were sensitive 100.0% to nitrofurantoin. Furthermore, 80 (79.2%) of the isolates had multidrug resistance, and 16 (26.7%) of both E. coli and Klebsiella spp. produced Extended spectrum β-lactamase (ESBL). In this study, a high prevalence of uropathogenic bacteria and multidrug resistance for commonly prescribed drugs were observed with a significant number of ESBL producers. Therefore, screening admitted gynecological patients, especially for those who have history of catheterization and UTI, by urine culture and antimicrobial susceptibility testing is important.
Type III Gustilo–Anderson open fracture does not justify routine prophylactic Gram-negative antibiotic coverage
Authors: Suzuki Takashi , Inui Takahiro , Sakai Miyoshi , Ishii Keisuke , Kurozumi Taketo , Watanabe Yoshinobu 
Published: May 2023

AbstractPostoperative surgical site infection (SSI) is common in open long bone fractures, so early administration of prophylactic antibiotics is critical to prevent SSI. However, the necessity of initial broad-spectrum coverage for Gram-positive and -negative pathogens remains unclear. The purpose of this study was to clarify the effectiveness of prophylactic broad-spectrum antibiotics in a large, national-wide sample. We reviewed an open fracture database of prospectively collected data from 111 institutions managed by our society. A retrospective cohort study was designed to compare the rates of deep SSI between narrow- and broad-spectrum antibiotics, which were initiated within three hours after injury. A total of 1041 type III fractures were evaluated at three months after injury. Overall deep SSI rates did not differ significantly between the narrow-spectrum group (43/538, 8.0%) and broad-spectrum group (49/503, 9.8%) (p = 0.320). During propensity score-matched analysis, 425 pairs were analyzed. After matching, no significant difference in the SSI rate was seen between the narrow- and broad-spectrum groups, with 42 SSIs (9.9%) and 40 SSIs (9.4%), respectively (p = 0.816). The probability of deep SSI was not reduced by broad-spectrum antibiotics compared with narrow-spectrum antibiotics in type III open long bone fractures.
Evidence of international transmission of mobile colistin resistant monophasic Salmonella Typhimurium ST34
Authors: Supa-amornkul Sirirak , Intuy Rattanaporn , Ruangchai Wuthiwat , Chaturongakul Soraya , Palittapongarnpim Prasit 
Published: May 2023

AbstractS. 4,[5],12:i:-, a monophasic variant of S. enterica serovar Typhimurium, is an important multidrug resistant serovar. Strains of colistin-resistant S. 4,[5],12:i:- have been reported in several countries with patients occasionally had recent histories of travels to Southeast Asia. In the study herein, we investigated the genomes of S. 4,[5],12:i:- carrying mobile colistin resistance (mcr) gene in Thailand. Three isolates of mcr-3.1 carrying S. 4,[5],12:i:- in Thailand were sequenced by both Illumina and Oxford Nanopore platforms and we analyzed the sequences together with the whole genome sequences of other mcr-3 carrying S. 4,[5],12:i:- isolates available in the NCBI Pathogen Detection database. Three hundred sixty-nine core genome SNVs were identified from 27 isolates, compared to the S. Typhimurium LT2 reference genome. A maximum-likelihood phylogenetic tree was constructed and revealed that the samples could be divided into three clades, which correlated with the profiles of fljAB-hin deletions and plasmids. A couple of isolates from Denmark had the genetic profiles similar to Thai isolates, and were from the patients who had traveled to Thailand. Complete genome assembly of the three isolates revealed the insertion of a copy of IS26 at the same site near iroB, suggesting that the insertion was an initial step for the deletions of fljAB-hin regions, the hallmark of the 4,[5],12:i:- serovar. Six types of plasmid replicons were identified with the majority being IncA/C. The coexistence of mcr-3.1 and blaCTX-M-55 was found in both hybrid-assembled IncA/C plasmids but not in IncHI2 plasmid. This study revealed possible transmission links between colistin resistant S. 4,[5],12:i:- isolates found in Thailand and Denmark and confirmed the important role of plasmids in transferring multidrug resistance.
Automated code compliance checking research based on BIM and knowledge graph
Authors: Peng Junlong , Liu Xiangjun 
Published: May 2023

AbstractAutomated code compliance checking plays an important role in moving the construction industry forward. While traditional drawing review relies on the identification of industry experts, the purpose of this study is to realize automatic code review by using BIM technology and knowledge graph technology. The method is based on knowledge graph to transform the specification provisions involved in the review of drawings into a computer-recognizable structured language using natural language processing technology to form a human–machine-readable knowledge graph pattern. For the review of BIM models, the BIM model information is exported and the global resource description framework of the building model is obtained in protégé, and the review report is finally obtained after mapping rules and review rules. Finally, the feasibility of the method is verified by an example. This study can effectively solve the problems of “manual dependency” and “inefficiency” in the process of review.
Effects of different doses of exercise and diet-induced weight loss on beta-cell function in type 2 diabetes (DOSE-EX): a randomized clinical trial
Authors: Legaard Grit E. , Lyngbæk Mark P. P. , Almdal Thomas P. , Karstoft Kristian , Bennetsen Sebastian L. , Feineis Camilla S. , Nielsen Nina S. , Durrer Cody G. , Liebetrau Benedikte , Nystrup Ulrikke , Østergaard Martin , Thomsen Katja , Trinh Beckey , Solomon Thomas P. J. , Van Hall Gerrit , Brønd Jan Christian , Holst Jens J. , Hartmann Bolette , Christensen Robin , Pedersen Bente K. , Ried-Larsen Mathias 
Published: May 2023

AbstractDiet-induced weight loss is associated with improved beta-cell function in people with type 2 diabetes (T2D) with remaining secretory capacity. It is unknown if adding exercise to diet-induced weight loss improves beta-cell function and if exercise volume is important for improving beta-cell function in this context. Here, we carried out a four-armed randomized trial with a total of 82 persons (35% females, mean age (s.d.) of 58.2 years (9.8)) with newly diagnosed T2D (<7 years). Participants were randomly allocated to standard care (n = 20), calorie restriction (25% energy reduction; n = 21), calorie restriction and exercise three times per week (n = 20), or calorie restriction and exercise six times per week (n = 21) for 16 weeks. The primary outcome was beta-cell function as indicated by the late-phase disposition index (insulin secretion multiplied by insulin sensitivity) at steady-state hyperglycemia during a hyperglycemic clamp. Secondary outcomes included glucose-stimulated insulin secretion and sensitivity as well as the disposition, insulin sensitivity, and secretion indices derived from a liquid mixed meal tolerance test. We show that the late-phase disposition index during the clamp increases more in all three intervention groups than in standard care (diet control group, 58%; 95% confidence interval (CI), 16 to 116; moderate exercise dose group, 105%; 95% CI, 49 to 182; high exercise dose group, 137%; 95% CI, 73 to 225) and follows a linear dose–response relationship (P > 0.001 for trend). We report three serious adverse events (two in the control group and one in the diet control group), as well as adverse events in two participants in the diet control group, and five participants each in the moderate and high exercise dose groups. Overall, adding an exercise intervention to diet-induced weight loss improves glucose-stimulated beta-cell function in people with newly diagnosed T2D in an exercise dose-dependent manner (NCT03769883).