bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Aerointolerant Gut Microbes and Butyrate Depletion in Severe Acute Malnutrition
Authors: Camara Aminata , Konate Salimata , Alou Maryam Tidjani , Armstrong Nicholas , Caputo Aurelia , Togo Amadou Hamidou , Niare Safiatou , Kone Abdoulaye Kassoum , Traore Issa , Levasseur Anthony , Doumbo Ogobara K. , Thera Mahamadou Ali , Million Matthieu 
Published: February 2025

AbstractSevere acute malnutrition (SAM) constitutes the leading risk for childhood mortality worldwide. Butyrate, a critical metabolite for mucosal immunity produced by anaerobic gut microbes, has been found to be dramatically depleted in children experiencing fatal outcomes related to SAM. However, the association between butyrate depletion and gut microbiota alteration has not yet been fully explored. Here, we performed a large group-matched case-control study in children aged 0-59 months in Mali. We compared faecal short-chain fatty acids (SCFAs) and gut microbiota from children with SAM and healthy controls, using gas chromatography-mass spectrometry and 16S rRNA v3v4 gene amplicon sequencing. A total of 253 children, including 143 with SAM and 110 controls, were included. Our findings revealed a dramatic imbalance in gut microbiota characterised by the predominance of aerotolerant micro-organisms in children with SAM, irrespective of age and sex. Importantly, aerointolerant species were totally absent in eight samples from children with SAM. A pronounced depletion of faecal valeric, butyric, propanoic and, to a lesser extent, acetic acid was observed, correlating with a ten-fold decrease in butyrate-producing microbes among the SAM population. This notable depletion of gut aerointolerant prokaryotes and butyrate levels persisted without being reversed at the time of discharge. Future therapeutic strategies aimed at addressing SAM should focus on restoring the gut anaerobic microbiota and faecal propionate and butyrate.
Investigating the contribution of circulating inflammatory cytokines on the link between obesity and COVID-19
Authors: Khamis Zahra J. , Karteris Emmanouil , Alhajeri Amani , Smith Steven G. , Blakemore Alexandra , Drenos Fotios 
Published: February 2025

AbstractBackgroundCoronavirus disease 2019 (COVID-19), is more severe in individuals with obesity. Furthermore, a cytokine storm was observed in many critically ill patients with COVID-19. Since adipose tissue secretes cytokines, we investigated whether cytokines mediate the effect of obesity on COVID-19 severity.MethodsUsing two-sample Mendelian randomization analyses we assessed the causal effect of body mass index (BMI) on COVID-19 severity. We then evaluated the BMI effect on 41 inflammatory cytokines, as well as on JAK-2, lymphocyte percentage and leptin. We also tested the relationship between these immunological factors and COVID-19 severity. The estimates obtained were used in a mediation analysis to understand the immunological factors linking BMI to COVID-19 severity.ResultsHigher BMI increased the risk of COVID-19 severity. BMI was also causally associated with 5 of the 41 inflammatory cytokines, HGF, TRAIL, IL 13, IL6, and IL 7. We identified TNF-α and IL-8 as the only two inflammatory cytokines associated with COVID-19 severity. Leptin-related genetic variation was associated with COVID-19 severity, but JAK-2 and lymphocyte percentage were not. We found no statistical evidence of mediation of immunological factors tested on the relationship between BMI and COVID-19 severity, although our estimate was 52.8%.ConclusionsWe replicated the previously reported association between BMI and COVID-19 severity. We identified the inflammatory cytokines elevated due to higher BMI. Other inflammatory cytokines showed evidence for increasing COVID-19 severity. However, we were unable to find statistical evidence of baseline levels of circulating cytokines, or additional factors involved in a cytokine storm i.e. JAK-2, lymphocyte percentage, and leptin, mediating the link between BMI and severe COVID-19. Although targeting specific cytokines will be of benefit in the general population, further work on cytokine levels during early phases of COVID-19 infection is needed to provide new approaches to decrease the risk of severe COVID-19 with higher BMI.
Effects of food insecurity on infant feeding confidence and practices during the COVID-19 pandemic and its waves
Authors: Hussain Maha , Hyun Jessica , Arduin Elena , Kyle Margaret H. , Abreu Wanda , Scripps Tessa , Nichols Presley H. , Khan Adrita , Glassman Melissa , Stockwell Melissa S. , Walzer Lauren , Dumitriu Dani , Fernández Cristina R. 
Published: February 2025

AbstractBackgroundThe COVID-19 pandemic has intensified economic hardships, with potential negative impacts on food insecurity and infant feeding beliefs and practices. The relationship between food insecurity and infant feeding beliefs and practices during the pandemic is not yet fully understood. Neither is how these relationships changed over the course of the waves of the pandemic. We examined these relationships in a cohort of infants born during the various waves of the COVID-19 pandemic in New York City (NYC).MethodsWe conducted a cross-sectional analysis of infants enrolled from birth into the COVID-19 Mother-Baby Outcomes (COMBO) study and born March 2020 to May 2024. We measured food insecurity in the prior 30 days with a 2-item survey adapted from Hunger Vital Sign™, infant feeding confidence at hospital discharge, and current infant feeding practices.Results40% of women in our sample had been exposed to prenatal SARS-CoV-2 infection and approximately 24% of mothers were food insecure. There was a significant association between food insecurity and prenatal SARS-CoV-2 infection, Spanish as one’s preferred language, and self-identifying as Latina. In unadjusted models of the entire sample, food insecurity was associated with formula feeding (p<0.001), but this relationship was no longer significant after adjusting for covariates (p=0.059). In comparing the first and second waves of the pandemic (March 2020-December 2021 vs. January 2022-May 2024), there was no significant difference in rate of food insecurity. When comparing different waves of the pandemic, food insecurity was associated with increased likelihood of formula feeding, even after adjusting for confounders.DiscussionFood insecurity was initially associated with feeding methods, but this relationship lost significance after adjusting for confounders. However, when analyzed separately, food insecurity was significantly linked to lower odds of exclusive breastfeeding during different waves of the pandemic, suggesting the influence of external factors like policy changes and social support variations. Other factors, such as maternal BMI, ethnicity, and delivery mode, were also significantly associated with breastfeeding practices, highlighting the need for targeted interventions to support breastfeeding, especially among food-insecure mothers.
A perturbation proteomics-based foundation model for virtual cell construction
Authors: Sun Rui , Qian Liujia , Li Yongge , Cheng Honghan , Xue Zhangzhi , Zhang Xuedong , Tan Lingling , Zhan Yuecheng , Hu Wenbin , Xiao Qi , Liu Zhiwei , Zhang Guangmei , Weinan E , Zhou Peijie , Wen Han , Zhu Yi , Guo Tiannan 
Published: February 2025

AbstractBuilding a virtual cell requires comprehensive understanding of protein network dynamics of a cell which necessitates large-scale perturbation proteome data and intelligent computational models learned from the proteome data corpus. Here, we generate a large-scale dataset of over 38 million perturbed protein measurements in breast cancer cell lines and develop a neural ordinary differential equation-based foundation model, namely ProteinTalks. During pretraining, ProteinTalks gains a fundamental understanding of cellular protein network dynamics. Our model encodes protein networks and exhibits consistently improved predictive accuracy across various downstream tasks, highlighting its generalization capabilities and adaptability. In cancer cells, ProteinTalks robustly predicts drug efficacy and synergy, identifies novel drug combinations, and, through its interpretability, uncovers resistance-associated proteins. When applied to more complex system, patient-derived tumor xenografts, ProteinTalks predicts potential responses to drugs. Its integration with clinical patient data enhances the prognosis prediction of breast cancer patients. Collectively, we present a foundational model based on proteome dynamics, offering potential for various downstream applications, including drug discovery, and providing a basis for developing virtual cells.
Neocortical Layer-5 tLTD Relies on Non-Ionotropic Presynaptic NMDA Receptor Signaling
Authors: Thomazeau Aurore , Rannio Sabine , Brock Jennifer A. , Wong Hovy Ho-Wai , Sjöström P. Jesper 
Published: February 2025

AbstractIn the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca2+when simultaneously depolarized and glutamate bound. Hebbian coincidence detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic NMDARs (preNMDARs) also exist. It is known that preNMDARs regulate neurotransmitter release, but precisely how remains poorly understood. Emerging evidence suggest that NMDARs can also signal non-ionotropically, without the need for Ca2+flux. At synapses between developing visual cortex layer-5 (L5) pyramidal cells (PCs), preNMDARs rely on Mg2+and Rab3-interacting molecule 1αβ (RIM1αβ) to regulate evoked release during periods of high-frequency firing, but they signal non-ionotropically via c-Jun N-terminal kinase 2 (JNK2) to regulate spontaneous release regardless of frequency. At the same synapses, timing- dependent long-term depression (tLTD) depends on preNMDARs but not on frequency. We therefore tested if tLTD relies on non-ionotropic preNMDAR signaling. We found that tLTD at L5 PC→PC synapses was abolished by pre- but not postsynaptic NMDAR deletion, cementing the view that tLTD requires preNMDARs. In agreement with non-ionotropic NMDAR signaling, tLTD prevailed after channel pore blockade with MK-801, unlike tLTP. Homozygous RIM1αβ deletion did not affect tLTD, but wash-in of the JNK2 blocker SP600125 abolished tLTD. Consistent with a presynaptic need for JNK2, a peptide blocking the interaction between JNK2 and Syntaxin-1a (STX1a) abolished tLTD if loaded pre- but not postsynaptically, regardless of frequency. Finally, low-frequency tLTD was not blocked by the channel pore blocker MK-801, nor by 7-CK, a non-competitive NMDAR antagonist at the co-agonist site. We conclude that neocortical L5 PC→PC tLTD relies on non-ionotropic preNMDAR signaling via JNK2/STX1a. Our study brings closure to long-standing controversy surrounding preNMDARs and highlights how the textbook view of NMDARs as ionotropic coincidence detectors in plasticity needs to be reassessed.
Non-causal association between α-klotho and human lifespan: evidence from multi-omics insights
Authors: Liu Xueyi , Yang Wulin 
Published: February 2025

AbstractWhile genetic evidence robustly associates longevity in non-human primates with Klotho protein, such a direct correlation in humans remains elusive. To scrutinize the potential causal link between genetically predicted Klotho levels and human lifespan, we devised a meticulous two-sample Mendelian randomization (MR) analysis, just leveraging single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTLs) as instrumental variables, meticulously analyzing the relationship between serum α-klotho and human longevity. By integrating MR estimates across diverse data sources using the fixed-effects inverse-variance weighted (IVW) approach, we consolidated our findings with a fixed-effects meta-analysis, fortified by sensitivity analyses embracing the simple median, weighted median, MR-Egger regression, and MR-pleiotropy residual sum and outlier assessments. Surprisingly, our genome-wide association MR analyses failed to uncover a causal association between Klotho and human lifespan, holding for both experimental and validation cohorts. Furthermore, the analysis grounded in protein quantitative trait loci also yielded no evidence of a causal link, with the sensitivity analyses consistently reinforcing the robustness of our findings. Hence, while animal models suggest a correlation between circulating Klotho and lifespan, this study demonstrates that genetically predicted levels of circulating α klotho do not exhibit a direct causal effect on human longevity.
The VExUS System Has a Limited Clinical Impact in the Evaluation and Management of Hypoosmolar Hyponatremia: A Single-Center Observational Study
Authors: Marques FJ. , Viejo-Boyano I. , González-Calero P. , Ferri A. , Gavilà M. , Mompó M. , Barrios P. , Cholbi-Vives E. , Peris-Fernandez M. 
Published: February 2025

AbstractBackgroundHyponatremia is the most frequent electrolyte disturbance in hospitalized patients, yet assessing volume status remains a diagnostic challenge. The Venous Excess Ultrasound (VExUS) system has been proposed as a noninvasive method to evaluate volume overload and guide management. However, data on its clinical impact in hypoosmolar hyponatremia are limited.ObjectiveTo investigate whether the VExUS system can support the management of acute hypoosmolar hyponatremia, detect discrepancies with physical examination in assessing volume status, and predict clinical outcomes.MethodsThis single-center observational study included adult inpatients with moderate or severe hypoosmolar hyponatremia (plasma sodium <=130 mEq/L). Patients underwent a standard clinical evaluation (history and physical examination) and a VExUS-based ultrasound assessment of at least two venous regions (inferior vena cava, hepatic veins, portal vein, or renal veins). Internal jugular vein measurements were used when feasible. The treating physicians of the patients were blinded to the ultrasound findings. Serum sodium levels were measured at 24, 48, and 96 hours. Treatments were based on existing clinical guidelines, and any changes in therapy were documented.ResultsTwenty-eight patients were enrolled, and two were excluded due to inadequate ultrasound data or new-onset cirrhosis. VExUS classification differed from clinical examination in 65.4 percent of patients (17 of 26), yet these discrepancies did not lead to significant differences in serum sodium trends or management changes at 24, 48, or 96 hours (p>0.05). Only four patients required therapeutic adjustments within 24 hours, and one displayed discrepant volume classifications. The VExUS system showed limited ability to distinguish euvolemia in patients with SIADH and demonstrated minimal correlation with laboratory parameters such as NT-proBNP and CA-125.ConclusionsWhile ultrasound assessment is noninvasive and potentially useful, this study found that discrepancies in VExUS-based volume status classification did not significantly alter clinical outcomes or treatment strategies in hospitalized patients with hypoosmolar hyponatremia. The VExUS method should not replace standard complementary evaluations recommended by hyponatremia guidelines, although it may have a niche role when ruling in or out hypervolemia in selected cases.
Ventral Tegmental Area as the Core Pathophysiological Hub in Bipolar Disorder: Evidence from Resting-State fMRI
Authors: Lee Tien-Wen 
Published: February 2025

AbstractObjectivesBipolar disorder (BPD) is a major and complex psychiatric condition, clinically characterized by euthymic, depressive, and manic phases. Through the concept of “dialectic neuroscience,” the ventral tegmental area (VTA) has been proposed as a potential key hub in BPD. This study utilized resting-state functional magnetic resonance imaging (rsfMRI) to investigate functional connectivity (FC) changes seeded by the VTA in BPD.MethodsMRI data from 98 participants in a publicly available dataset were analyzed (49 stable BPD patients and 49 healthy controls). Using the dopamine receptor D1 distribution template from JuSpace, the representative voxel of the VTA in the midbrain was identified based on the highest correlation with the D1 template. This voxel served as the seed for FC map construction. The FC maps were Fisher-transformed and compared statistically using an independent two-sample t-test.ResultsSignificant deviations in BPD were observed in brain regions that were highly consistent with the projections of the VTA, including the ventral and medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and nucleus accumbens.ConclusionsThe FC analysis provided empirical support for the VTA theory in BPD. The role of VTA abnormalities in contributing to the manifestation of opposing polarities within a single disorder was discussed, offering insights into the potential physiological mechanisms and genesis of BPD. The framework of dialectic neuroscience may provide a valuable approach for developing guiding brain theories in psychiatric disorders.
Spatially regulated mRNA decay sharpens expression patterns in theDrosophilaembryo
Authors: Love Jennifer C. , Beadle Lauren Forbes , Sutcliffe Catherine , Rattray Magnus , Ashe Hilary L. 
Published: February 2025

AbstractThe regulation of mRNA decay is important for numerous cellular and developmental processes. Here, we use the patterning geneeven-skipped(eve) in the earlyDrosophilaembryo to investigate the contribution of mRNA decay to shaping mature expression patterns. Through P-body colocalisation analysis and mathematical modelling of live and fixed imaging data, we present evidence thatevemRNA stability is regulated across stripe 2, with enhanced mRNA decay at the edges of the stripe. To manipulate mRNA stability, we perturbed mRNA decay in the embryo by optogenetic degradation of the 5’ to 3’ exoribonuclease Pacman (Pcm). Depleting Pcm results in larger P-bodies, which accumulateevemRNAs, and disruptedeveexpression patterns. Overall, these data show howevemRNA instability can function with transcriptional regulation to define sharp expression domain borders. We discuss how spatially regulated mRNA stability may be widely used to sculpt expression patterns during development.
Diverse mechanisms of DDX3Y suppression by DDX3X
Authors: Xu Xiaolu , Wei Shuo 
Published: February 2025

AbstractThe DEAD-box RNA helicase DDX3X has important roles in development and disease. Loss of DDX3X during developmental and pathological processes such as tumorigenesis can lead to compensatory upregulation of the close paralog DDX3Y in males, which may underlie the sexual dimorphism displayed by some DDX3X-associated diseases. However, how DDX3X cross-regulates DDX3Y remains largely unknown. Here, we investigated the regulation of DDX3Y by DDX3X in two male-derived human cancer cell lines, HCT116 and U87MG. Depletion of DDX3X in HCT116 cells results in moderately increased DDX3Y mRNA and protein, in part due to stabilization ofDDX3Ytranscripts. Conversely, reduction of DDX3X in U87MG cells markedly upregulates DDX3Y protein without affecting its mRNA, mainly by enhancing DDX3Y protein stability. We further show that DDX3X physically interacts with DDX3Y. DDX3Y is much less stable than DDX3X in U87MG cells, and substitution of two lysine residues in DDX3Y with the corresponding arginine in DDX3X stabilizes DDX3Y. Thus, the compensatory upregulation of DDX3Y following DDX3X loss can occur at either transcript or protein level, suggesting complex and cell type-specific cross-regulation between these X- and Y-linked paralogs to keep the total DDX3 dosage in check.
Evaluation of Antioxidant Anticancer and Antimicrobial Activities of Datura Leaf Extracts: A Microbiological Perspective
Authors: Sheoran Sumit , Arora Swati 
Published: February 2025

AbstractDatura, a genus of flowering plants, has long been used in traditional medicine owing to its pharmacological properties. This study investigated the antioxidant and antimicrobial activities of Datura leaf extracts by using in vitro assays. Antioxidant potential was evaluated using standard methods, while antimicrobial activity was assessed against various bacterial and fungal strains using the disk diffusion method. The results demonstrated significant antioxidant properties and broad-spectrum antimicrobial activity, supporting the potential of Datura as a source of bioactive compounds for pharmaceutical applications. The findings of this study elucidate the potential of datura leaf extracts as natural alternatives to synthetic antioxidants and antimicrobial agents in various industries. Further research is warranted to explore the specific bioactive compounds responsible for these properties and to investigate their mechanisms of action. Additionally, future studies should focus on optimizing extraction methods to enhance the potency and efficacy of Datura-derived products for potential therapeutic applications.
Enhanced Computational and Experimental Approaches for Comparative Analysis of the Human Mycobiome
Authors: Begum Neelu , Lee Sunjae , Almeida Mathieu , Engstrand Lars , Patel S. Vishal C. , Uhlen Mathias , Ehrlich Dusko , Shoiae Saeed , Moyes David L. 
Published: February 2025

AbstractThe mycobiome is now recognized as a critical part of the human microbial ecosystem, playing a significant role in both health and disease. Mycobiome research is currently in its infancy and relies on fungal-specific primers with challenges in bioinformatics to accurately determine the structure of the mycobiota community. In addition, the majority of computational and experimental methods currently in use have been optimized for bacteria rather than for fungi. Here, we provide a comparative analysis of extraction methodologies for metagenome sequencing and subsequent bioinformatic analysis that will enhance fungal species identification. We utilized cultured mock fungal communities, including both yeast and mold species, to evaluate the efficiency of extraction protocols. We further enhanced computational analysis of the mycobiome, using mock and human metagenome data together with our curated catalogue consisting of 984 fungal genomes specific to the human mycobiome. Application of this optimised workflow for oral and gut samples of healthy individuals detected of novel species fromPucciniaandLentinusgenera among the established presence ofMalassezia,Rhizophagus,CandidaandSaccharomycesgenera. In addition,Enterocytozoon,was identified specifically in the gut mycobiome. Our pipeline enabled the comprehensive sampling of all fungal genes in a microbial community within a human sample minimising bias, reducing errors and artefacts from amplification, and providing accurate diversity and abundance data for the human mycobiome.