bluuebunny/crossref_metadata_2025_split huggingface dataset:
De-medicalising gluten-free products through a subsidy card scheme: a qualitative study of service users
Authors: Sha’aban Abubakar , Mazzaschi Francesca , Ingram Beti-Jane , Joseph-Williams Natalie 
Published: December 2024

AbstractIntroductionCoeliac disease requires a strict gluten-free diet to prevent complications. In the late 1960s, Gluten free foods (GFF) became available on prescription to support adherence when these foods were scarce in shops. Today, gluten-free foods are more accessible in large supermarkets, making it easier for patients to obtain them without prescriptions. In 2019, Hywel Dda University Health Board introduced the GFF subsidy card as an alternative to prescriptions, a method still used by other health boards in Wales.AimsThis study aimed to explore individuals’ perspectives on a new subsidy card scheme for GFF, identify key barriers and facilitators, and provide recommendations to enhance the scheme’s implementation and effectiveness.MethodA qualitative approach was employed, involving in-depth interviews with coeliac patients and parents of coeliac children. Participants included current users of the subsidy card, those relying on prescriptions, and individuals who opted out of the card scheme.ResultsParticipants using the subsidy card valued its flexibility, variety of products, and convenience over the prescription system. Challenges included managing card balances, limited retailer acceptance, and geographical disparities. Non-users appreciated the potential for increased choice and mostly showed interest in switching but some raised concerns about inflation, misuse, and the additional burden on taxpayers.ConclusionMost participants view the subsidy card as an acceptable alternative to GFF prescriptions. To improve the subsidy card uptake, recommendations include enhancing digital tools for balance management, card value reviews, expanding retailer partnerships, promoting safer food practices, targeted communication, and ensuring prescription continuity for those who prefer it. These measures can optimize the scheme’s impact and better support individuals with coeliac disease.
Connectome-based symptom mapping andin silicorelated gene expression in children with autism and/or attention-deficit/hyperactivity disorder
Authors: Segura Patricia , Pagani Marco , Bishop Somer L. , Thomson Phoebe , Colcombe Stanley , Xu Ting , Factor Zekiel Z. , Hector Emily C. , Kim So Hyun , Lombardo Michael V. , Gozzi Alessandro , Castellanos Xavier F. , Lord Catherine , Milham Michael P. , Di Martino Adriana 
Published: December 2024

ABSTRACTClinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patternsin silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to:(i)have greater rate of variance in autism and ADHD, and(ii)be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined phenomena to shared presentations at the macroscale circuit- and genomic-levels among children with diagnoses of autism and ADHD.
Genetic Variants and Alteration inTranscription Factor 7-Like 2 (TCF7L2)mRNA level in Ischemic Stroke Patients: An Indian Scenario
Authors: Sadhukhan Dipanwita , Roy Arunima , Nath Sukla , Basu Esha , Mukherjee Joydeep , Ghosh Kartik Chandra , Banerjee Tapas Kumar , Krishnan Prasad , Chatterjee Sourya Kishore , Desai Soaham , Patel Vishal Ajitbhai , Ray Debes , Hui Subhra Prakash , Gupta Soma , Biswas Arindam 
Published: December 2024

ABSTRACTBackgroundDiabetes and Hyperlipidemia are major risk factors for stroke across the world population.TCF7L2, a key player of the WNT signaling pathway shows genetic association with both metabolic disturbances. However, its role in stroke pathogenesis (if any) is not well characterized.ObjectivesThus, here we aim to (a) examine and correlate dysregulation ofTCF7L2expression with diabetes or hyperlipidemia-associated Ischemic Stroke, (b) identify genetic risk variants in theTCF7L2gene and (c) establish a correlation betweenTCF7L2mRNA expressions with biochemical parameters.MethodsBased on radiological findings for Ischemic Stroke, a total of 50 unrelated subjects were recruited with diverse biochemical parameters for TCF7L2 mRNA expression study in PBMC, followed by correlation with fasting blood sugar and lipid profile. Furthermore, mutation screening and genetic association studies (rs7901695 & rs7903146) were performed among 326 cases and 258 controls from India.ResultsHere, we observed a significant downregulation ofTCF7L2gene expression among hyperlipidemic stroke patients than cases and control without dyslipidemia but no change between the cases with different diabetic statuses. Moreover, a strong negative correlation betweenTCF7L2mRNA level and total blood cholesterol but not for FBS was identified. The rs7901695T/C appeared as a promising genetic risk factor for stroke among eastern Indians.ConclusionTherefore, we can suggest that alteration inTCF7L2leading to stroke pathogenesis is more associated with hyperlipidemia than diabetes among Indians. Its expression level in PBMC is influenced by rs7901695T/C and holds a good promise to be used as a diagnostic marker.
Tools of Hibernation Measurement and Interpretation (TOHMIN) for quantifying various values from body temperature fluctuation during hibernation
Authors: Otsuka Reo , Shimoyama Yutaro , Nakagawa Satoshi , Yamaguchi Yoshifumi 
Published: December 2024

AbstractHibernation is a fascinating physiological phenomenon that dramatically reduces basal metabolism and thermogenesis, resulting in a large deviation in body temperature (Tb) from homeothermic ranges in mammals. Although high-resolution long-term Tb recording in wild or laboratory animals has become possible through data loggers, few standardized methods to analyze details of hibernation patterns are available, making it difficult to reproduce and compare the results across different studies and species. To facilitate the analysis of hibernation patterns and accelerate hibernation research, we developed an open-source program, tools of hibernation measurement and interpretation (TOHMIN). As a proof of concept, we analyzed a dataset from two pilot studies on (1) the effects of distinct diets on hibernation patterns and (2) differences in hibernation patterns between males and females in a mammalian hibernator, Syrian hamster (Mesocricetus auratus), and found previously undetectable fine-scale differences in hibernation patterns. First, different types of diets affected the duration of periodic arousal. Second, females maintained higher body temperatures during periodic arousal than males. Third, the duration of the pre-hibernation period was negatively correlated with the hibernation period for this species. Thus, TOHMIN accelerates studies to assess the effects of various experimental manipulations on hibernation phenotypes in mammals.
Age and sex influence seed dispersal of native and non-native plants by Lion-tailed MacaquesMacaca silenus
Authors: Bindu K , Kumara Honnavalli N. , Naniwadekar Rohit 
Published: December 2024

ABSTRACTWhile interspecific variation in seed dispersal, a critical ecosystem process in tropical forests, is relatively well-studied, intraspecific variation as a consequence of differences in body size, foraging behaviours, and ranging patterns among age-sex categories within a species is relatively understudied. Among vertebrates, primates play a critical role in seed dispersal and exhibit behavioural differences between age and sex categories, making them a suitable study system for intraspecific variation in seed dispersal. Lion-tailed macaquesMacaca silenus, an endemic and predominantly frugivorous primate species in the Western Ghats Biodiversity Hotspot, provide an excellent model for such studies. We examined the influence of age and sex on 1) the diversity and 2) the quantity of native and non-native fruits consumed, 3) the number of seeds dispersed, 4) seed dispersal distance, and 5) seed deposition substrates in lion-tailed macaques. We conducted over 375 hours of focal animal watches, distributed evenly across adult males, females, and subadults. Our findings showed that subadults consumed a higher diversity of native and non-native fruits than females and males. They dispersed fewerFicusseeds than females. We found differences in the proportions of non-native fruits in the diets of different age- sex categories. Males consumed moreCoffea liberica, whereas females and subadults fed onCoffeaandLantana. We found weak evidence suggesting that males were more likely to disperseFicusseeds on trees, which are suitable substrates forFicusestablishment. Our study highlights that age and sex significantly influence seed dispersal patterns of native and non- native species by an endemic, frugivorous primate species with potential influence on recruitment.
Chromosome engineering points to thecis-acting mechanism of chromosome arm-specific telomere length setting and robustness of plant phenotype, chromatin structure and gene expression
Authors: Helia Ondřej , Matúšová Barbora , Havlová Kateřina , Hýsková Anna , Lyčka Martin , Beying Natalja , Puchta Holger , Fajkus Jiří , Fojtová Miloslava 
Published: December 2024

AbstractThe study investigates the impact of targeted chromosome engineering on telomere dynamics, chromatin structure, gene expression, and phenotypic stability inArabidopsis thaliana. Using precise CRISPR/Cas-based engineering, reciprocal translocations of chromosome arms were introduced between non-homologous chromosomes. The subsequent homozygous generations of plants were assessed for phenotype, transcriptomic changes and chromatin modifications near translocation breakpoints, and telomere length maintenance. Phenotypically, translocated lines were indistinguishable from wild-type plants, as confirmed through morphological assessments and principal component analysis. Gene expression profiling detected minimal differential expression, with affected genes dispersed across the genome, indicating negligible transcriptional impact. Similarly, ChIPseq analysis showed no substantial alterations in the enrichment of key histone marks (H3K27me3, H3K4me1, H3K56ac) near junction sites or across the genome. Finally, bulk and arm-specific telomere lengths remained stable across multiple generations, except for minor variations in one translocation line. These findings highlight the remarkable genomic and phenotypic robustness ofA. thalianadespite large-scale chromosomal rearrangements. The study offers insights into thecis-acting mechanisms underlying chromosome arm-specific telomere length setting and establishes the feasibility of chromosome engineering for studies of plant genome evolution and crop improvement strategies.Significance statementThis study demonstrates the robustness ofArabidopsis thalianain maintaining telomere stability, chromatin integrity, and wild-type phenotype despite large-scale chromosomal translocations. It underscores the potential of chromosome engineering in advancing genome evolution research and crop improvement, contributes to a deeper understanding of genome dynamics, and opens new avenues for precision breeding in plants.
Protein language model pseudolikelihoods capture features of in vivo B cell selection and evolution
Authors: van Ginneken Daphne , Samant Anamay , Daga-Krumins Karlis , Agrafiotis Andreas , Kladis Evgenios , Reddy Sai T. , Yermanos Alexander 
Published: December 2024

AbstractB cell selection and evolution play crucial roles in dictating successful immune responses. Recent advancements in sequencing technologies and deep-learning strategies have paved the way for generating and exploiting an ever-growing wealth of antibody repertoire data. The self-supervised nature of protein language models (PLMs) has demonstrated the ability to learn complex representations of antibody sequences and has been leveraged for a wide range of applications including diagnostics, structural modeling, and antigen-specificity predictions. PLM-derived likelihoods have been used to improve antibody affinities in vitro, raising the question of whether PLMs can capture and predict features of B cell selection in vivo. Here, we explore how general and antibody-specific PLM-generated sequence pseudolikelihoods (SPs) relate to features of in vivo B cell selection such as expansion, isotype usage, and somatic hypermutation (SHM) at single-cell resolution. Our results demonstrate that the type of PLM and the region of the antibody input sequence significantly affect the generated SP. Contrary to previous in vitro reports, we observe a negative correlation between SPs and binding affinity, whereas repertoire features such as SHM, isotype usage, and antigen specificity were strongly correlated with SPs. By constructing evolutionary lineage trees of B cell clones from human and mouse repertoires, we observe that SHMs are routinely among the most likely mutations suggested by PLMs and that mutating residues have lower absolute likelihoods than conserved residues. Our findings highlight the potential of PLMs to predict features of antibody selection and further suggest their potential to assist in antibody discovery and engineering.Key points-In contrast to previous in vitro work (Hie et al., 2024), we observe a negative correlation between PLM-generated sequence pseudolikelihood (SP) and binding affinity. This contrast can be explained by the inherent antibody germline bias posed by PLM training data and the difference between in vivo and in vitro settings.-Our findings also reveal a considerable correlation between SPs and repertoire features such as the V-gene family, isotype, and the amount of somatic hypermutation (SHM). Moreover, labeled antigen-binding data suggested that SP is consistent with antigen-specificity and binding affinity.-By reconstructing B cell lineage evolutionary trajectories, we detected predictable features of SHM using PLMs. We observe that SHMs are routinely among the most likely mutations suggested by PLMs and that mutating residues have lower absolute likelihoods than conserved residues.-We demonstrate that the region of antibody sequence (CDR3 or full V(D)J) provided as input to the model, as well as the type of PLM used, influence the resulting SPs.
Effect of OASL on oxaliplatin-induced immunogenic cell death in gastric cancer via the cGAS-STING signaling pathway
Authors: Zhang Lingling , Liu Yi , Yang Haiying , Liu Luguang , Wang Longgang , Chai Jie , Zhao Weizhu , Sun Dong 
Published: December 2024

AbstractThis study investigates the role of 2’-5’ oligoadenylate synthetase-like (OASL) in Oxaliplatin (OXA)-induced immunogenic cell death (ICD) in Gastric cancer (GC) cells through the cGAS-STING signaling pathway. Knockdown of OASL enhanced ICD expression, while overexpression had the opposite effect. RNA sequencing of OASL-knockdown and control GC cells treated with OXA revealed significant enrichment of the second messenger signaling pathway (cGAMP). cGAMP could directly activate STING as a second messenger, and cGAS was a key synthetic enzyme upstream of cGAMP. Next, the role of OASL in OXA-induced ICD in GC cells was validated through the cGAS-STING signaling pathway. The Co-IP and immunofluorescence results confirmed that the OASL and cGAS proteins can bind directly. Further research validated these findings in vivo. Results show that OASL regulates OXA-induced ICD in GC cells via the cGAS-STING pathway, impacting chemosensitivity. The findings suggest new targets and strategies for improving GC therapy by modulating OASL expression to enhance OXA sensitivity through immunogenic mechanisms.
Discovery of molecular glues that bind FKBP12 and novel targets using DNA-barcoded libraries
Authors: Zandi Trevor A. , Romanowski Michael J. , Viscomi Jessica S. , Tan Zher Yin , Tong Bingqi , Bonazzi Simone , Zécri Frédéric J. , Schreiber Stuart L. , Michaud Gregory A. 
Published: December 2024

ABSTRACTMolecular glues are small molecules that engage their target and presenter proteins cooperatively. FKBP12 molecular glues (FK506 and rapamycin) were discovered several decades ago and have been used clinically, but our understanding of the breadth of FKBP12 molecular glues and targets has yet to be fully revealed. To identify novel targets of FKBP12 molecular glues, we constructed and screened a multi-million-member non-macrocyclic FKBP12-ligand DNA-encoded library using 25 structurally distinct proteins. Synthesis and validation of selected hits in biophysical and cell-based assays confirm FKBP12-dependent molecular-glue recruitment to bromodomain-containing protein 9 (BRD9) and quinoid dihydropteridine reductase (QDPR). One glue showed no measurable binding to QDPR alone but had appreciable binding in the presence of FKBP12 using either purified proteins or intact cells. The sites of recruitment were characterized with mutational analysis, competition-based methods and X-ray crystallography. The results of this study confirm that FKBP12-binding DELs can yield novel molecular glues generating highly selective FKBP12-target protein interactions.
Clonally expanded IgG antibody-secreting cells preferentially target influenza nucleoprotein following homologous and heterologous infections
Authors: Agrafiotis Andreas , Kuhn Raphael , Panetti Camilla , Venerito Marco , Phandee Hathaichanok , Stalder Lucas , Shlesinger Danielle , D’Arcy Vittoria Martinolli , Hong Kai-Lin , van Ginneken Daphne , Genovese Alessandro , Joller Nicole , Oxenius Annette , Reddy Sai T. , Yermanos Alexander 
Published: December 2024

AbstractInfection with influenza virus remains a significant global health concern due to its ability to acquire mutations at key antigenic sites to escape antibody recognition. While germinal center (GC) and memory B cells have been well studied following influenza infection, the clonal dynamics of antibody secreting cells (ASCs), particularly those within the bone marrow (BM) niche that are responsible for serum immune protection, remain poorly understood. Here, we combine single-cell RNA (scRNA) and B cell receptor (BCR) sequencing to characterize individual ASCs following various Influenza exposure histories. We find that BM repertories are populated by highly expanded and class-switched ASCs following Influenza infection with similar transcriptional and repertoire characteristics regardless of homologous or heterologous infection histories. By combining single-cell analysis with monoclonal antibody expression and characterization, we find that a large proportion of the expanded IgG-, but not IgA-, ASC repertoire demonstrates specificity to influenza nucleoprotein (NP). Together, our data reveal the complex relationship between BM ASC repertoires, mucosal humoral immune responses, and BCR antigen specificity during influenza infection.
PathoFact 2.0: An Integrative Pipeline for Predicting Antimicrobial Resistance Genes, Virulence Factors, Toxins and Biosynthetic Gene Clusters in Metagenomes
Authors: Sunyer Júlia Ortís , Delgado Luis F. , Hickl Oskar , Laczny Cedric C. , May Patrick , Wilmes Paul 
Published: December 2024

AbstractSummaryAntimicrobial resistance genes (ARGs) and virulence factors (VFs) are central contributors to the global health crisis surrounding drug-resistant infections. PathoFact, a bioinformatics pipeline introduced in 2021, provides insights into ARGs, VFs, and bacterial toxins from metagenomic data. However, recent advancements in bioinformatics highlight the need for an updated version of PathoFact. We introduce PathoFact 2.0, an enhanced pipeline for improved ARG, VF, and toxin prediction. Key updates include an updated machine learning (ML) model for VF identification, a new ML model for toxin identification, expanded hidden Markov model profiles, and the antiSMASH 7.0 integration for predicting biosynthetic gene clusters. These upgrades make PathoFact 2.0 a more powerful, user-friendly platform for predicting microbiome-based pathogenicity and resistance, offering a crucial tool for better understanding and addressing the challenges posed by antimicrobial resistance and infectious diseases.Availability and ImplementationPathoFact 2.0 is available for download athttps://gitlab.lcsb.uni.lu/ESB/PathoFact2/.
Apocarotenoid signaling regulates meristem activity and shapes shoot and root lateral organ formation inArabidopsis
Authors: Sierra Julio , Escobar-Tovar Lina , Napsucialy-Mendivil Selene , Oltehua-López Omar , Dubrovsky Joseph G. , McQuinn Ryan P. , Leon Patricia 
Published: December 2024

AbstractPlant carotenoids are precursors to phytohormones and signaling molecules, playing critical roles in plant development, an emerging area of research. This study investigates the function of the undefined apocarotenoid ACS1 signal in modulating plant development, particularly its impact on the morphologenesis of lateral organs and apical meristems. By modulating ACS1 levels under varying light conditions, we demonstrate its dynamic role in leaf and root development. Notably the characteristic radial leaf morphology of theclb5mutant reverts to normal even days post-germination, demonstrating that ACS1 is not a toxic signal but rather a key component of a biogenic retrograde signaling pathway.Transcriptomic analysis ofclb5seedlings at different post-germination stages underscores the critical role of ACS1 during specific developmental window. The expression profile of this mutant correlates with a proplastid stage, where even the expression of most of the genes involved in plastid biogenesis are downregulated. Furthermore, ACS1 disrupts the expression of diverse developmentally important genes, including those participating in auxin transport and signaling, leading to impaired meristem maintenance and inhibiting leaf expansion.The effects of ACS1 extends beyond photosynthetic tissues, impacting shoot and apical root meristem organization. In particular, ACS1 affects columella cell pattering, disrupting normal gravitropic responses. These findings demonstrate that ACS1 dynamically regulates both leaf and root development, as well as meristem activity.This study provides new insights into the role ofcis-carotenoids as retrograde signals, functioning very early in the plastid differentiation and emphasizes the significance of plastid retrograde signaling in plant growth and development.