bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human genetic variation reveals FCRL3 is a lymphocyte receptor forYersinia pestis
Authors: Keener Rachel M. , Shi Sam , Dalapati Trisha , Wang Liuyang , Reinoso-Vizcaino Nicolás M , Luftig Micah A. , Miller Samuel I. , Wilson Timothy J. , Ko Dennis C. 
Published: December 2024

AbstractYersinia pestisis the gram-negative bacterium responsible for plague, one of the deadliest and most feared diseases in human history. This bacterium is known to infect phagocytic cells, such as dendritic cells and macrophages, but interactions with non-phagocytic cells of the adaptive immune system are frequently overlooked despite the importance they likely hold for human infection. To discover human genetic determinants ofY. pestisinfection, we utilized nearly a thousand genetically diverse lymphoblastoid cell lines in a cellular genome-wide association study method called Hi-HOST (High-throughput Human in-vitrO Susceptibility Testing). We identified a nonsynonymous SNP, rs2282284, inFc receptor like 3 (FCRL3) associated with bacterial invasion of host cells (p=9×10-8).FCRL3belongs to the immunoglobulin superfamily and is primarily expressed in lymphocytes. rs2282284 is within a tyrosine-based signaling motif, causing an asparagine-to-serine mutation (N721S) in the most common FCRL3 isoform. Overexpression of FCRL3 facilitated attachment and invasion of non-opsonizedY. pestis.Additionally, FCRL3 colocalized withY. pestisat sites of cellular attachment, suggesting FCRL3 is a receptor forY. pestis.These properties were variably conserved across the FCRL family, revealing molecular requirements of attachment and invasion, including an Ig-like C2 domain and a SYK interaction motif. Direct binding was confirmed with purified FCRL5 extracellular domain. Following attachment, invasion ofY. pestiswas dependent on SYK and decreased with the N721S mutation. Unexpectedly, this same variant is associated with risk of chronic hepatitis C virus infection in BioBank Japan. Thus,Y. pestishijacks FCRL proteins, possibly taking advantage of an immune receptor to create a lymphocyte niche during infection.
Dispersal evolution can only rescue a limited set of species from climate change
Authors: Kamal Peter , Thompson Patrick L. , Lewis Natalie , Fronhofer Emanuel A. 
Published: December 2024

LAY SUMMARYGlobal biodiversity is under threat from climate change. A key process for understanding species’ responses to climate change is dispersal: the movement of an individual to reproduce somewhere other than its birthplace. Dispersal allows species to shift their range to more suitable habitats when conditions change. In addition, dispersal can evolve rapidly, especially during such range shifts. Here, we explore whether rapid dispersal evolution can save species from climate change. We identify a small set of cases in which this is theoretically possible. Our results outline general characteristics of species and their environments that make such rescue possible and therefore aid both with our fundamental understanding and applied conservation measures.
NicheTrans: Spatial-aware Cross-omics Translation
Authors: Wang Zhikang , Lin Senlin , Zou Qi , Cui Yan , Han Chuangyi , Li Yida , Li Jianmin , Zhao Yi , Gao Rui , Song Jiangning , Yuan Zhiyuan 
Published: December 2024

ABSTRACTSpatial omics technologies have revolutionized our studies on tissue architecture and cellular interactions at single-cell resolution. While spatial multi-omics approaches offer unprecedented insights into complex biological systems, their widespread adoption is hindered by technical challenges, specialized requirements, and limited accessibility. To address these limitations, we present NicheTrans, the first spatially-aware cross-omics translation method and a flexible Transformer-based multi-modal deep learning framework. Unlike existing single-cell (non-spatial) translation methods, NicheTrans uniquely incorporates both cellular microenvironment information and flexible integration of multi-modal data, such as morphology and prior knowledge. We validated NicheTrans across diverse biological cases: Parkinson’s Disease (PD), Alzheimer’s Disease (AD), breast cancer, and lymph nodes. Our approach demonstrated superior performance compared to existing single-cell methods, highlighting the crucial role of spatial and multi-modal information in cross-omics translation. Through NicheTrans, we uncovered spatial multi-omics domains that were not detectable through single-omics analysis alone. Model interpretation revealed key molecular relationships, including gene programs associated with dopamine metabolism and amyloid β-associated cell states. Additionally, using translated protein markers as spatial landmarks, we quantified the spatial organization of key glial cell subtypes in the AD brain. NicheTrans represents a powerful tool for generating comprehensive spatial multi-omics insights from more accessible single-omics measurements, making multi-omics analysis more feasible for the broader research community.
Time-of-day related fluctuations of self-belief formation
Authors: Mayer Annalina V. , Schröder Alexander , Czekalla Nora , Müller-Pinzler Laura , Rosenbusch Laura , Paulus Frieder M. , Oster Henrik , Sayk Clara , Kammerer Mathias , Wilhelm-Groch Ines , Krach Sören 
Published: December 2024

AbstractTime of day influences a variety of human cognitive processes, including attention, executive functions and memory formation, as well as affective experiences and mood. However, circadian modulations of self-related learning and belief formation, which are highly affected by emotional states, remain poorly understood.Here, we present results from exploratory post-hoc analyses on data aggregated from five studies assessing the formation of self-related ability beliefs. A total ofN=242 healthy participants completed a validated learning task at different times of the day, during which they continuously received feedback on their performance. Computational modeling was applied to quantify participants’ learning behavior during the task.Results suggest an association between time-of-day and self-belief formation, showing that participants who were tested in the evening (7:00-9:59 p.m.) updated their self-beliefs more strongly in response to the received feedback compared to those tested in the afternoon (1:00-3:59 p.m.). Evidence from additional models indicated that these differences were driven by non-linear, rhythmic changes in self-belief formation across different times of the day.Future studies should systematically examine within-subject fluctuations in self-belief formation across the day and address the influence of individual factors such as chronotype, age, mood and sleep quality. Understanding circadian modulations of self-related belief formation could contribute to optimized interventions for conditions characterized by maladaptive self-beliefs, such as depression, as well as in academic contexts.
Humoral correlate of vaccine-mediated protection from tuberculosis identified in humans and non-human primates
Authors: Kelkar Natasha S. , Curtis Nicholas C. , Lahey Timothy P. , Wieland-Alter Wendy , Stout Jason E. , Larson Erica C. , Jauro Solomon , Scanga Charles A. , Darrah Patricia A. , Roederer Mario , Seder Robert A. , von Reyn C. Fordham , Lee Jiwon , Ackerman Margaret E. 
Published: December 2024

AbstractDevelopment of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection againstMycobacterium tuberculosis(Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)- immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain (M. obuense) sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB. In humans, antibodies to MOS also scale with vaccine dose, are elicited by BCG vaccination, are observed during TB disease, and demonstrate cross-reactivity with Mtb; in NHP, MOS-specific antibodies scale with dose and serve as a CoP mediated by BCG vaccination. Collectively, this study reports a novel humoral CoP and specific antigenic targets that may be relevant to achieving vaccine-mediated protection from TB.
Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss
Authors: Ghezzi Lorenzo , Pech Ulrike , Schoovaerts Nils , Poovathingal Suresh , Davie Kristofer , Lamote Jochen , Praschberger Roman , Verstreken Patrik 
Published: December 2024

ABSTRACTParkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in thesubstantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear.Pink1is mutated in familial PD and through unbiased single-cell sequencing of the entire brain ofDrosophila Pink1models, we observed significant gene deregulation in ensheathing glia (EG); cells that share functional similarities with oligodendrocytes. We found that the loss ofPink1leads to the activation of EG, similar to the reactive response of EG seen upon nerve injury. Using cell-type specific transcriptomics, we identified deregulated genes in EG as potential functional modifiers. Specifically, downregulating two trafficking factors, Rab7 and Vps13, also mutated in PD, or the direct regulators of Rab7, Mon1 and Ccz1, specifically in EG was sufficient to rescue neuronal function and protect against dopaminergic synapse loss. Our findings demonstrate that Pink1 loss in neurons triggers an injury response in EG, and that Pink1 loss in EG in turn disrupts neuronal function. Vesicle trafficking components, which regulate membrane interactions between organelles within EG, play a crucial role in maintaining neuronal health and preventing dopaminergic synapse loss. Our work highlights the essential role of glial support cells in the pathogenesis of PD and identifies vesicle trafficking within these cells as a key point of convergence in disease progression.
Early identification of Family Medicine residents at risk of failure using Natural Language Processing and Explainable Artificial Intelligence
Authors: Joshi Abhisht , Mortezaagha Pouria , Inkpen Diana , Seale Edward , Archibald Douglas , Noel Kendall , Rahgozar Arya 
Published: December 2024

AbstractBackgroundDuring residency, each resident is observed and receives feedback based on their performance. Residency training is demanding, with a few residents struggling in their academic performance. A competency-based residency training program’s success depends on its ability to identify residents with difficulty during their first year of post-graduate education and to provide them with timely intervention and support.ObjectiveIn large training programs such as Family Medicine, identifying residents at risk of failing their certification exams is difficult. We develop a AI system using state-of-the-art technologies in Machine Learning (ML), Deep Learning (DL), Natural Language Processing (NLP) and Explainable AI (XAI) to detect at-risk residents automatically.MethodsWe implemented ML, DL and NLP models for the prediction and its performance analysis. The target variable chosen for the prediction was the determination of whether the resident would fail or pass their certification exam. XAI was used to enhance the understanding of the model’s inner workings.ResultsIn total, there were 1382 data points of residents. The champion model, Support Vector Machine (SVM), achieved an accuracy of 89.05% and an F1 score of 74.54 for the multiclass classification when multimodal (text and tabular) data was used. This model outperformed the models that only used qualitative or quantitative data exclusively.ConclusionCombining qualitative and quantitative data represents a novel approach and has provided better classification results. This research demonstrates the feasibility of an automated AI system for the early identification of residents at risk of academic struggle.
Optimal Control Strategies for Mitigating Antibiotic Resistance: Integrating Virus Dynamics for Enhanced Intervention Design
Authors: Dere Zainab , Cogan N. G. , Karamched Bhargav R. 
Published: December 2024

AbstractGiven the global increase in antibiotic resistance, new effective strategies must be developed to treat bacteria that do not respond to first or second line antibiotics. One novel method uses bacterial phage therapy to control bacterial populations. Phage viruses replicate and infect bacterial cells and are regarded as the most prevalent biological agent on earth. This paper presents a comprehensive model capturing the dynamics of wild-type bacteria (S), antibiotic-resistant bacteria (R), and infective (I) strains, incorporating virus inclusion. Our model integrates biologically relevant parameters governing bacterial birth rates, death rates, and mutation probabilities and incorporates infection dynamics via contact with a virus. We employ an optimal control approach to study the influence of virus inclusion on bacterial population dynamics. Through numerical simulations, we establish insights into the stability of various system equilibria and bacterial population responses to varying infection rates. By examining the equilibria, we reveal the impact of virus inclusion on population trajectories, describe a medical intervention for antibiotic-resistant bacterial infections through the lense of optimal control theory, and discuss how to implement it in a clinical setting. Our findings underscore the necessity of considering virus inclusion in antibiotic resistance studies, shedding light on subtle yet influential dynamics in bacterial ecosystems.
Effectiveness of the PAS Scale for Diagnosing the Severity of Acute Appendicitis in Children: A Cohort Study
Authors: Edgar Sucso-Noa 
Published: December 2024

AbstractWhat’s Known on This SubjectAppendicitis is an acute inflammatory process that affects the appendix, one of the common causes of abdominal pain in children in emergency. Being one of the most common conditions faced by surgeons.The PAS scale, a clinical score for acute appendicitis, is among the most popular for use in children for diagnosis. The severity of appendicitis subclassified as simple appendicitis (congested or suppurated) vs complicated appendicitis (gangrenous or perforated) could be predicted with a PAS scale ≥8.What This Study AddsTests logistic regression models as a basis for developing more complex models to improve prediction of complicated acute appendicitis in children.BackgroundThe Pediatric Appendicitis Score (PAS) is a highly utilized diagnostic tool for acute appendicitis in pediatric patients. The severity of appendicitis subclassified as simple appendicitis (congested or suppurated) vs complicated appendicitis (gangrenous or perforated) could be predicted with a PAS scale ≥8.MethodsThe type of study of the present research, according to Altman Douglas, is: Observational, Retrospective y Longitudinal. The design is cohort-type. The population was evaluated, 86 children aged 4-14 years with a preoperative diagnosis of appendicitis, grouped into 2 groups: complicated appendicitis (43) and simple appendicitis (43) exposed to the PAS≥8 or PAS 8.ResultsThe effectiveness of the PAS≥8 scale for diagnosing the severity of appendicitis showed a predictive diagnostic accuracy of 59.3% and increases the likelihood of severity by 2.246 times (CI:95% 0.917-5.50 p=0.077) in the predictive model. There were statistically significant differences in cough/hop/percussion Tenderness, migration of pain, anorexia, leukocytosis and neutrophilia, between scale PAS≥8 vs PAS<8.ConclusionThe PAS≥8 scale alone is not sufficient to diagnose the severity of acute appendicitis, with 59.3% predictive diagnostic accuracy and increasing the likelihood of presenting the severity of appendicitis by 2.246 times.
The ratio of plasma pTau217 to Aβ42 outperforms individual measurements in detecting brain amyloidosis
Authors: Lehmann Sylvain , Gabelle Audrey , Duchiron Marie , Busto Germain , Morchikh Mehdi , Delaby Constance , Hirtz Christophe , Mondesert Etienne , Cristol Jean-Paul , Barnier-Figue Genevieve , Perrein Florence , Turpinat Cédric , Jurici Snejana , Bennys Karim ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2024

AbstractIMPORTANCEEarly detection of brain amyloidosis (Aβ+) is pivotal for diagnosing Alzheimer’s disease (AD) and optimizing patient management, especially in light of emerging treatments. While plasma biomarkers are promising, their combined diagnostic value through specific ratios remains underexplored.OBJECTIVETo evaluate the diagnostic accuracy of plasma pTau isoform (pTau181 and pTau217) to Aβ42 ratios in detecting Aβ+ status.DESIGN, SETTING, AND PARTICIPANTSThis study included 423 participants from the multicenter prospective ALZAN cohort, recruited for cognitive complaints. Aβ+ status was determined using cerebrospinal fluid (CSF) biomarkers. Validation of the key findings was performed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, where Aβ+ status was determined using PET imaging.EXPOSURESPlasma biomarkers (pTau181, pTau217, Aβ40, Aβ42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALZAN cohort, the impact of confounding factors such as age, renal function, ApoE4 status, body mass index, and the delay between blood collection and processing was also evaluated to assess their influence on biomarker concentrations and diagnostic performance.MAIN OUTCOMES AND MEASURESThe primary outcome was the diagnostic performance of plasma biomarkers and their ratios for detecting Aβ+ status. Secondary outcomes included the proportion of patients classified as low, intermediate, or high risk for Aβ+ using a two-cutoff approach.RESULTSThe pTau181/Aβ42 ratio matched the diagnostic performance of pTau217 with AUC of 0.911 (0.880-0.936). The pTau217/Aβ42 ratio demonstrated the highest diagnostic accuracy in the ALZAN cohort, with an AUC of 0.927 (0.898-0.950), outperforming individual biomarkers. Both ratios effectively mitigated confounding factors, such as variations in renal function, and were particularly excellent in identifying Aβ+ status in individuals with early cognitive decline. Validation in the ADNI cohort confirmed these findings, with consistent performance across different measurement methods. The two-cutoff workflow using pTau217/Aβ42 reduced the intermediate-risk zone from 16% to 8%, enhancing stratification for clinical decision-making.CONCLUSIONS AND RELEVANCEThe pTau217/Aβ42 ratio offers superior diagnostic accuracy for detecting Aβ+ compared to individual biomarkers and reduces diagnostic uncertainty. These findings highlight the clinical utility of plasma biomarker ratios for early AD detection, paving the way for broader implementation in clinical and research settings.
The activity of soil microbial taxa in the rhizosphere predicts the success of root colonization
Authors: Harris Jennifer E. , Bledsoe Regina B. , Guha Sohini , Omari Haneen , Crandall Sharifa G. , Burghardt Liana T. , Couradeau Estelle M. 
Published: December 2024

AbstractPlant-beneficial microbes have great potential to improve sustainability in agriculture. Still, managing beneficial microbes is challenging because the impact of microbial dormancy on community assembly across the soil, rhizosphere, and endosphere is poorly understood. We address this gap with the first documented use of Biorthogonal Non-Canonical Amino Acid Tagging (BONCAT) to probe active microbes in the soil-to-root gradient. Using nodule-forming legumeTrifolium incarnatum,we confirmed that BONCAT is suitable for labeling endospheric microbes with microscopy. Next, we coupled BONCAT to Flow Cytometer Activated Cell Sorting (FACS) and 16S rRNA amplicon sequencing to probe patterns of microbial activity and the structure of the active microbial community across the soil, rhizosphere, root, and nodule with a native soil microbial community. As expected, we found x10 higher microbial activity in the endosphere than in the rhizosphere or bulk soil, likely due to increased plant resources. Finally, we revealed that microbial activity in the rhizosphere was significantly associated with successful endosphere colonization, more so than microbial abundance alone. This last finding has implications for the development of microbial inoculants, suggesting colonizing plant roots is linked to a microbe’s ability to overcome dormancy once deployed in the soil.
Hospital Waste Management: An Overview of the Situation in Health Districts outside Yaounde in the Centre Region, Cameroon
Authors: Edzamba Michel Franck , Cheuyem Fabrice Zobel Lekeumo , Sime Paule Sandra Djomo , Minlo Fernande Eliane Nyangon , Sani Bertille Ngon , Nkongo Florence Kissougle , Mossus Tatiana 
Published: December 2024

AbstractBackgroundHospital waste management is an important process that must be handled with care. This is because of the potential risks it represents for human health and the environment. A good understanding of the processes and legislation involved is an important asset, especially in developing countries. In order to assess the level of application of regulations, this study describes the quality of hospital waste management in health districts outside Yaounde in the Centre region.MethodologyA descriptive cross-sectional study was conducted in public health facilities of 24 Health Districts in the Centre Region from February 1 to March 31, 2024. Sampling was consecutive and non-exhaustive. Data were collected using a Google form from health facility managers and/or staff in charge of hospital hygiene. The data was coded and analyzed using R Statistics version 4.3.1.ResultsA total of 61 participants coming from 20 Health Districts of the Central Region were enrolled in the study. With a sex ratio (M/F) of 0.9, most of the participants were paramedical staff. Less than 10% of the participants were Medical-sanitary technician. Most of the respondents reported that waste was sorted at source. However, nearly half (45%) carried out regular checks at this stage. More than two-thirds of responded (78%) reported that household waste was packed in buckets and black bags. More than half of the infectious waste was packaged in bin buckets (57%). More than one-third (39%) of the waste was collected daily. The vast majority (93%) reported that they disposed of waste on site. Nearly 5% reported disposing of waste in a public landfill. A small proportion (7.3%) of health facilities had an incinerator.ConclusionDespite the efforts made, there are still significant shortcomings in the hospital waste management strategy of the health facilities visited. Stakeholders need technical, financial and material support if they are to meet international standards.