bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias
Authors: Moura Sofia , Hartl Ingrid , Brumovska Veronika , Calabrese Peter P , Yasari Atena , Striedner Yasmin , Bishara Marina , Mair Theresa , Ebner Thomas , Schütz Gerhard J , Sevcsik Eva , Tiemann-Boege Irene 
Published: February 2024

Abstract
Delayed fatherhood results in a higher risk of inheriting a new germline mutation that might result in a congenital disorder in the offspring. In particular, some FGFR3 mutations increase in frequency with age, but there are still a large number of uncharacterized FGFR3 mutations that could be expanding in the male germline with potentially early- or late-onset effects in the offspring. Here, we used digital polymerase chain reaction to assess the frequency and spatial distribution of 10 different FGFR3 missense substitutions in the sexually mature male germline. Our functional assessment of the receptor signaling of the variants with biophysical methods showed that 9 of these variants resulted in a higher activation of the receptor´s downstream signaling, resulting in 2 different expansion behaviors. Variants that form larger subclonal expansions in a dissected postmortem testis also showed a positive correlation of the substitution frequency with the sperm donor's age, and a high and ligand-independent FGFR3 activation. In contrast, variants that measured high FGFR3 signaling and elevated substitution frequencies independent of the donor's age did not result in measurable subclonal expansions in the testis. This suggests that promiscuous signal activation might also result in an accumulation of mutations before the sexual maturation of the male gonad with clones staying relatively constant in size throughout time. Collectively, these results provide novel insights into our understanding of the mutagenesis of driver mutations and their resulting mosaicism in the male germline with important consequences for the transmission and recurrence of associated disorders.
Turnovers of Sex-Determining Mutation in the Golden Pompano and Related Species Provide Insights into Microevolution of Undifferentiated Sex Chromosome
Authors: Guo Liang , Malara Danilo , Battaglia Pietro , Waiho Khor , Davis D Allen , Deng Yu , Shen Zhongyuan , Rao Ke 
Published: February 2024

Abstract
The suppression of recombination is considered a hallmark of sex chromosome evolution. However, previous research has identified undifferentiated sex chromosomes and sex determination by single SNP in the greater amberjack (Seriola dumerili). We observed the same phenomena in the golden pompano (Trachinotus ovatus) of the same family Carangidae and discovered a different sex-determining SNP within the same gene Hsd17b1. We propose an evolutionary model elucidating the turnover of sex-determining mutations by highlighting the contrasting dynamics between purifying selection, responsible for maintaining W-linked Hsd17b1, and neutral evolution, which drives Z-linked Hsd17b1. Additionally, sporadic loss-of-function mutations in W-linked Hsd17b1 contribute to the conversion of W chromosomes into Z chromosomes. This model was directly supported by simulations, closely related species, and indirectly by zebrafish mutants. These findings shed new light on the early stages of sex chromosome evolution.
Postural Control Characteristics in Alzheimer’s Disease, Dementia With Lewy Bodies, and Vascular Dementia
Authors: Fujita Kosuke , Sugimoto Taiki , Noma Hisashi , Kuroda Yujiro , Matsumoto Nanae , Uchida Kazuaki , Kishino Yoshinobu , Sakurai Takashi 
Published: February 2024

Abstract

Background
Dementia often results in postural control impairment, which could signify central nervous system dysfunction. However, no studies have compared postural control characteristics among various types of dementia. This study aimed to compare static postural control in patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and vascular dementia (VaD).

Methods
Cross-sectional relationship between the clinical diagnoses (AD, DLB, VaD, or normal cognition [NC]) of outpatients at a memory clinic and their upright postural control characteristics were examined. In the postural control test, participants were instructed to maintain a static upright standing on a stabilometer for 60 seconds under the eyes-open and eyes-closed conditions. Forty postural control parameters, including distance, position, and velocity in the anterior–posterior and medio–lateral directions, derived from the trajectory of the center of mass sway, were calculated. The characteristics of each type of dementia were compared to those of NC, and the differences among the 3 types of dementia were evaluated using linear regression models.

Results
The study included 1 789 participants (1 206 with AD, 111 with DLB, 49 with VaD, and 423 with NC). Patients with AD exhibited distinct postural control characteristics, particularly in some distance and velocity parameters, only in the eyes-closed condition. Those with DLB exhibited features in the mean position in the anterior–posterior direction. In patients with VaD, significant differences were observed in most parameters, except the power spectrum.

Conclusions
Patients with AD, DLB, and VaD display disease-specific postural control characteristics when compared to cognitively normal individuals.
Unsupervised clustering of catalogue-driven features for characterizing temporal evolution of labquake stress
Authors: Karimpouli Sadegh , Kwiatek Grzegorz , Martínez-Garzón Patricia , Dresen Georg , Bohnhoff Marco 
Published: February 2024

SUMMARYEarthquake forecasting poses significant challenges, especially due to the elusive nature of stress states in fault systems. To tackle this problem, we use features derived from seismic catalogues obtained from acoustic emission (AE) signals recorded during triaxial stick-slip experiments on natural fractures in three Westerly granite samples. We extracted 47 physically explainable features from AE data that described spatio-temporal evolution of stress and damage in the vicinity of the fault surface. These features are then subjected to unsupervised clustering using the K-means method, revealing three distinct stages with a proper agreement with the temporal evolution of stress. The recovered stages correspond to the mechanical behaviour of the rock, characterized as initial stable (elastic) deformation, followed by a transitional stage leading to an unstable deformation prior to failure. Notably, AE rate, clustering-localization features, fractal dimension, b-value, interevent time distribution, and correlation integral are identified as significant features for the unsupervised clustering. The systematically evolving stages can provide valuable insights for characterizing preparatory processes preceding earthquake events associated with geothermal activities and waste-water injections. In order to address the upscaling issue, we propose to use the most important features and, in case of normalization challenge, removing non-universal features, such as AE rate. Our findings hold promise for advancing earthquake prediction methodologies based on laboratory experiments and catalogue-driven features.
Comorbidity Between Inflammatory Bowel Disease and Asthma and Allergic Diseases: A Genetically Informed Study
Authors: Gong Tong , Brew Bronwyn K , Lundholm Cecilia , Smew Awad I , Harder Arvid , Kuja-Halkola Ralf , Ludvigsson Jonas F , Lu Yi , Almqvist Catarina 
Published: February 2024

Abstract

Background
Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods.

Methods
Within-individual and familial co-aggregation analysis was applied to 2 873 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap.

Results
IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn’s disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation ra = 0.06; 95% CI, −0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (re = 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn’s disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12).

Conclusions
We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema.
Relationship Between Hepatitis C Infection and Treatment Status and Coronavirus Disease 2019–Related Hospitalizations in Georgia
Authors: Aslanikashvili Ana , Rylander Charlotta , Manjavidze Tinatin , Gamkrelidze Amiran , Baliashvili Davit , Anda Erik Eik 
Published: February 2024

Abstract

Background
The aim of this study was to evaluate the impact of hepatitis C virus (HCV) infection and treatment status on coronavirus disease 2019 (COVID-19)–related hospitalizations in Georgia.

Methods
We analyzed 2020–2021 Georgian health registry data for COVID-19–positive individuals and categorized the data by HCV infection and treatment status. Logistic regression was used to assess the strengths of the associations.

Results
Treated individuals with HCV had lower odds of COVID-19–related hospitalization compared to anti-HCV-negative individuals, while untreated HCV-viremic and anti-HCV-positive nonviremic individuals had higher odds.

Conclusions
HCV treatment prior to COVID-19 infection was associated with lower odds of COVID-19–related hospitalization, highlighting the benefits of HCV management in the context of the pandemic.
Gut microbiota contribute to variations in honey bee foraging intensity
Authors: Vernier Cassondra L , Nguyen Lan Anh , Gernat Tim , Ahmed Amy Cash , Chen Zhenqing , Robinson Gene E 
Published: February 2024

Abstract
Gut microbiomes are increasingly recognized for mediating diverse biological aspects of their hosts, including complex behavioral phenotypes. Although many studies have reported that experimental disruptions to the gut microbial community result in atypical host behavior, studies that address how gut microbes contribute to adaptive behavioral trait variation are rare. Eusocial insects represent a powerful model to test this, because of their simple gut microbiota and complex division of labor characterized by colony-level variation in behavioral phenotypes. Although previous studies report correlational differences in gut microbial community associated with division of labor, here, we provide evidence that gut microbes play a causal role in defining differences in foraging behavior between European honey bees (Apis mellifera). We found that gut microbial community structure differed between hive-based nurse bees and bees that leave the hive to forage for floral resources. These differences were associated with variation in the abundance of individual microbes, including Bifidobacterium asteroides, Bombilactobacillus mellis, and Lactobacillus melliventris. Manipulations of colony demography and individual foraging experience suggested that differences in gut microbial community composition were associated with task experience. Moreover, single-microbe inoculations with B. asteroides, B. mellis, and L. melliventris caused effects on foraging intensity. These results demonstrate that gut microbes contribute to division of labor in a social insect, and support a role of gut microbes in modulating host behavioral trait variation.
Repurposing cinacalcet suppresses multidrug-resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR
Authors: Fang Zu-Ye , Zhang Zi-Yuan , Zheng Yun-Dan , Lei Dan , Zhuang Jianpeng , Li Nan , He Qing-Yu , Sun Xuesong 
Published: February 2024

Abstract

Background
MDR Staphylococcus aureus infections, along with the severity of biofilm-associated infections, continue to threaten human health to a great extent. It necessitates the urgent development of novel antimicrobial and antibiofilm agents.

Objectives
To reveal the mechanism and target of cinacalcet as an antibacterial and antimicrobial agent for S. aureus.

Methods
Screening of non-antibiotic drugs for antibacterial and antibiofilm properties was conducted using a small-molecule drug library. In vivo efficacy was assessed through animal models, and the antibacterial mechanism was studied using quantitative proteomics, biochemical assays, LiP-SMap, BLI detection and gene knockout techniques.

Results
Cinacalcet, an FDA-approved drug, demonstrated antibacterial and antibiofilm activity against S. aureus, with less observed development of bacterial resistance. Importantly, cinacalcet significantly improved survival in a pneumonia model and bacterial clearance in a biofilm infection model. Moreover, the antibacterial mechanism of cinacalcet mainly involves the destruction of membrane-targeted structures, alteration of energy metabolism, and production of reactive oxygen species (ROS). Cinacalcet was found to target IcaR, inhibiting biofilm formation through the negative regulation of IcaADBC.

Conclusions
The findings suggest that cinacalcet has potential for repurposing as a therapeutic agent for MDR S. aureus infections and associated biofilms, warranting further investigation.
Temocillin for febrile urinary tract infections caused by ESBL-producing Enterobacteriaceae in children: a monocentric exposed/non-exposed study
Authors: Bayart Jules , Drouet Juliette , Peycelon Matthieu , Mariani Patricia , Le Roux Enora , Husain Maya , Agar Julien , Bonacorsi Stéphane , Caseris Marion 
Published: February 2024

Abstract

Objectives
To compare the efficacy of temocillin with standard of care (SOC) for treatment of ESBL-producing Enterobacteriaceae (ESBL-E) febrile urinary tract infection (ESBL-E FUTI) in children.

Methods
A monocentric retrospective study of children hospitalized with confirmed ESBL-E FUTI from January 2015 to May 2022 was conducted, comparing clinical cure and a 3 month relapse between two groups of patients: ‘exposed’ patients (EP) and ‘non-exposed’ patients (NEP) to temocillin. EP received temocillin for at least 3 days. They were matched (1:1 ratio) on age group, sex and presence of uropathy with NEP who received SOC antibiotic therapy.

Results
Thirty-six temocillin-treated children (EP) were matched with 36 SOC children (NEP); 72.2% were under 2 years old (n = 52) and 75.0% had a congenital uropathy (n = 54). EPs had more FUTI history (97.2%, n = 35) than NEPs (61.1%, n = 22) (P &lt; 0.01). Clinical cure rate was 98.6% overall, with no difference between the two groups, as for the FUTI relapse rate, which was 37.1% for EPs versus 27.8% for NEPs (P = 0.45). In bivariate analyses, factors associated with relapses were congenital uropathy (91.3% versus 66.7%, P = 0.04) and subtypes of uropathy, with refluxing uropathy and posterior urethral valves being the more prevalent. Median duration of hospitalization was longer in the EPs (8.0 versus 5.0 days) (P = 0.01).

Conclusions
The high clinical cure rate and comparable outcomes suggest that temocillin may be an effective therapeutic alternative to standard treatment for ESBL-E FUTI in children.
BioLORD-2023: semantic textual representations fusing large language models and clinical knowledge graph insights
Authors: Remy François , Demuynck Kris , Demeester Thomas 
Published: February 2024

Abstract

Objective
In this study, we investigate the potential of large language models (LLMs) to complement biomedical knowledge graphs in the training of semantic models for the biomedical and clinical domains.

Materials and Methods
Drawing on the wealth of the Unified Medical Language System knowledge graph and harnessing cutting-edge LLMs, we propose a new state-of-the-art approach for obtaining high-fidelity representations of biomedical concepts and sentences, consisting of 3 steps: an improved contrastive learning phase, a novel self-distillation phase, and a weight averaging phase.

Results
Through rigorous evaluations of diverse downstream tasks, we demonstrate consistent and substantial improvements over the previous state of the art for semantic textual similarity (STS), biomedical concept representation (BCR), and clinically named entity linking, across 15+ datasets. Besides our new state-of-the-art biomedical model for English, we also distill and release a multilingual model compatible with 50+ languages and finetuned on 7 European languages.

Discussion
Many clinical pipelines can benefit from our latest models. Our new multilingual model enables a range of languages to benefit from our advancements in biomedical semantic representation learning, opening a new avenue for bioinformatics researchers around the world. As a result, we hope to see BioLORD-2023 becoming a precious tool for future biomedical applications.

Conclusion
In this article, we introduced BioLORD-2023, a state-of-the-art model for STS and BCR designed for the clinical domain.
Broad-spectrum defenders: γδ T cells take on a multitude of immune challenges
Authors: Freen-van Heeren Julian J 
Published: February 2024

Abstract
A recent article in Proceedings of the National Academy of Sciences investigated γδ T cell antigen specificity in mice and humans, in which the authors show that γδ T cell antigen specificity is not constrained to one epitope. Rather, γδ T cells recognize a broad range of diverse antigens containing similar chemical structures or properties. In this News and Views, the importance of γδ T cell antigen polyspecificity during immune responses is highlighted.
Comparative transcriptome profiling across 9 tissues in 2 pika species provides new insights and resources to interpret plateau adaptation
Authors: Zhang Ruobing , Mu Danping , Wu Xinlai , Feijó Anderson , Wen Zhixin , Cheng Jilong , Xia Lin , Yang Qisen , Shan Wenjuan , Ge Deyan 
Published: February 2024

Abstract
As an endemic species of the Qinghai–Tibet Plateau, the Plateau Pika (Ochotona curzoniae) exhibits adaptation to the extremely high-altitude environment and possesses a number of distinct physiological characteristics. In order to explore potential mechanisms underlying the adaptation of plateau pikas, we investigate transcriptomic differences across tissues (heart, liver, spleen, lung, kidney, muscle, cerebellum, left brain, and right brain) of the Plateau Pika, in a comparative framework. We analyze possible mechanisms of adaptive evolution by including a transcriptome analysis across the 9 tissues from 3 male and 4 female O. curzoniae and contrasting results with the 8 male and 4 female Gansu Pika (O. cansus) that inhabits the lower middle altitudes. Differential expression and protein–protein interaction network analyses were used to identify the differentially expressed genes and their primary functions. By analyzing interspecific differences, we identified significant adaptive transcriptional changes in the heart, lung, and spleen of the Plateau Pika. Specifically, upregulated genes in these tissues not only show a substantial association with apoptosis and DNA damage repair, but also demonstrate apparent enrichment in biological pathways related to energy metabolism and immune regulation. The majority of downregulated genes exhibit decreased activity in metabolic pathways particularly in muscle, spleen, kidney, and brain tissues. We further reveal the pivotal gene interaction networks of the 9 tissues. Our study provides valuable insight into adaptive mechanisms underlying evolution of Plateau Pika at extreme altitudes.
Dietary interventions in cancer: a systematic review of all randomized controlled trials
Authors: Ilerhunmwuwa Nosakhare Paul , Abdul Khader Abul Hasan Shadali , Smith Calvin , Cliff Edward R Scheffer , Booth Christopher M , Hottel Evevanne , Aziz Muhammad , Lee-Smith Wade , Goodman Aaron , Chakraborty Rajshekhar , Mohyuddin Ghulam Rehman 
Published: February 2024

Abstract

Background
Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all randomized controlled trials (RCTs) investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results.

Methods
This systematic review identified all RCTs conducted before January 2023 testing dietary interventions in patients with cancer. Assessed outcomes included quality of life, functional outcomes, clinical cancer measurements (eg, progression-free survival, response rates), overall survival, and translational endpoints (eg, inflammatory markers).

Results
In total, 252 RCTs were identified involving 31 067 patients. The median sample size was 71 (interquartile range 41 to 118), and 80 (32%) studies had a sample size greater than 100. Most trials (n = 184, 73%) were conducted in the adjuvant setting. Weight or body composition and translational endpoints were the most common primary endpoints (n = 64, 25%; n = 52, 21%, respectively). Direct cancer measurements and overall survival were primary endpoints in 20 (8%) and 7 (3%) studies, respectively. Eight trials with a primary endpoint of cancer measurement (40%) met their endpoint. Large trials in colon (n = 1429), breast (n = 3088), and prostate cancer (n = 478) each showed no effect of dietary interventions on endpoints measuring cancer.

Conclusion
Most RCTs of dietary interventions in cancer are small and measure nonclinical endpoints. Although only a small number of large RCTs have been conducted to date, these trials have not shown an improvement in cancer outcomes. Currently, there is limited evidence to support dietary interventions as a therapeutic tool in cancer care.
Gas content and evolution of a sample of YSO associations at d ≲ 3.5 kpc from the Sun
Authors: Zhou Ji-Xuan , Li Guang-Xing , Chen Bing-Qiu 
Published: February 2024

ABSTRACT
Young Stellar Objects (YSO) are newly formed stars from molecular clouds. They stay close to where they were born and serve as good tracers to study gas and star formation. During cloud evolution, young massive stars can disrupt the surrounding gas through stellar feedback, changing the gas distribution. We study the distribution of the gas around a sample of YSO associations located at $d \lesssim 3.5 \,\,\rm kpc$ from the Sun by comparing the location and morphology between 12CO (J  = 1–0) emission, Planck 870 $\mu$m maps and YSO associations. Based on the spatial distribution of the gas compared to that of the YSOs, we classify the YSO associations into six types: direct, close, bubble, complex, diffuse, and clean associations. The complex associations are large structures consisting of both gas-rich and gas-poor segments. We study the velocity dispersion-size relation towards different association types. From the ratio between different types, we estimate a feedback time of ≈ 1.7 Myr in the solar neighbourhood. The sample sets a solid foundation to explore the relationship between interstellar medium evolution, star formation, and Galaxy structure.