bluuebunny/crossref_metadata_2025_split huggingface dataset:
TREATMENT OUTCOMES AND ASSOCIATED FACTORS AMONG SEVERELY MALNOURISHED UNDER-FIVE CHILDREN ADMITTED TO JINKA GENERAL HOSPITAL, SOUTH ARI ZONE, SOUTH E THIOPIA REGION
Authors: Tukura Turufat 
Published: November 2024

AbstractIntroductionRecurrent drought has contributed to household level food insecurity that resulted in malnutrition in the zone. This contributed to high prevalence of children malnutrition.At the Jinka General Hospital the treatment outcomes and associated factors were not identified by research where there are high admissions of children with severe acute malnutrition with significant mortality. Therefore, this study was aimed to conduct a retrospective review of records of children admitted with severe acute malnutrition to Jinka General Hospital to assess treatment outcomes and associated factors at stabilization centreObjectiveThis study was to assess treatment outcomes and associated factors in children with severe acute malnutrition admitted to Jinka General Hospital.MethodA hospital record-based data analysis study was conducted to assess the treatment outcomes and associated factors of severe acute malnutrition among a total of 453 children aged 0 to 6 months and 6–59 months old. Severe acute malnutrition registration book and patient charts was used as a source of data. Data was entered into STATA version 16 for analysis. Ordered logistic regression was used to analyse treatment outcome with successful (cured), death (poor) and unknown (unsatisfactory). Variables at P-value <0.05 were considered as predictors of treatment outcome among children admitted with Severe Acute Malnutrition (SAM).ResultsRehydration Solution for Malnutrition (ResoMal), educational status of mother, exclusive breast feeding, returned defaulter, severe wasting with bilateral Pitting oedema (Marasmus-Kwashiorkor), Infants 0-6 Months of age, and Unconscious were the substantial predictors of death among children admitted with SAM. Whereas therapeutic milk F-100, Gentamycin, sex of the child (male), rural residence, new admission, bilateral Pitting Oedema +++(Kwashiorkor), and some dehydrations were the predictors of recovery among the SAM cases.Conclusionexclusive breast feeding, and educational status of mother are the prevention of malnutrition. Targeted intervention of cases based on the enter category to stabilization centres is imperative for better outcome. The study also highlighted that the cure rate was below the SPHERE treatment outcome standard and death rate was at alarming rate according to SPHERE standard and national treatment outcome indicator. Thus, the study recommends management of SAM children through adherence with National Guideline for the Management of Acute Malnutrition in Ethiopia and empowering of women and girls to improve their literacy. This will contribute to improve household level food preparation practice and services to prevent malnutrition among children.
RING1 dictates GSDMD-mediated inflammatory response and host susceptibility to pathogen infection
Authors: Li Yuanyuan , Gao Wenqing , Qiu Yuxin , Pan Jiasong , Guo Qingqing , Liu Xuehe , Geng Lu , Shen Yajie , Hu Zhidong , Li Suhua , Liu Shanshan , Yang Hua , Ge Baoxue , Fan Xiaoyong , Chen Xiangjun , Li Jixi 
Published: November 2024

AbstractRING1 is an E3 ligase component of the polycomb repressive complex 1 (PRC1) with known roles in chromatin regulation and cellular processes such as apoptosis and autophagy. However, its involvement in inflammation and pyroptosis needs to be better characterized. Here, we found that human RING1, but not RING2, promoted K48-linked ubiquitination of Gasdermin D (GSDMD) and acted as a negative regulator of pyroptosis and bacterial infection.Ring1knockout mice increased the bacterial loads and mortality rate by treatment ofS. typhimurium. Upon infection byM. tuberculosis(Mtb) H37Rv strain, RING1 deletion initially reduced bacterial loads but later increased lung inflammation and impaired immune defense responses in mice. Also,Ring1knockout exacerbated acute sepsis induced by lipopolysaccharide (LPS). Mechanistically, RING1 directly interacts with GSDMD and ubiquitinates the K51 and K168 sites of GSDMD for K48-linked proteasomal degradation, thereby inhibiting pyroptosis. Inhibition of RING1 E3 ligase activity by mutation or small molecular compound increased GSDMD level and cell death during pyroptosis. Our findings reveal that RING1 dictates GSDMD-mediated inflammatory response and host susceptibility to pathogen infection, highlighting RING1 as a potential therapeutic target for combating infectious diseases.Graphic AbstractHighlightsE3 ubiquitin ligase RING1 targets GSDMD for proteasomal degradation.Mice lacking RING1 are more vulnerable toS. typhimuriuminfection and LPS- induced sepsis.In the early stages ofM. tuberculosis(Mtb) infection,Ring1-/-mice exhibit efficient bacterial clearance.Chronic inflammation inRing1-/-mice impairs the ability to control Mtb in the late stages of infection.
Nucleosome repositioning in cardiac reprogramming
Authors: Harris Sonalí , Baksh Syeda S. , Wang Xinghua , Anwar Iqra , Pratt Richard E. , Dzau Victor J. , Hodgkinson Conrad P. 
Published: November 2024

AbstractEarly events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen in response to reprogramming. Histone modification and re-positioning would be expected to open up chromatin on lineage-specific genes and this can be ascertained by studying nucleosome architecture. We have recently developed a set of tools to identify significant changes in nucleosome architecture which we used to study skeletal muscle differentiation. In this report, we have applied these tools to understand nucleosome architectural changes during fibroblast to cardiac muscle reprogramming. We found that nucleosomes surrounding the transcription start sites of cardiac muscle genes induced during reprogramming were insensitive to reprogramming factors as well as to agents which enhance reprogramming efficacy. In contrast, significant changes in nucleosome architecture were observed distal to the transcription start site. These regions were associated with nucleosome build-up. In summary, investigations into nucleosome structure do not support the notion that fibroblasts to cardiac muscle cell reprogramming involves chromatin opening and suggests instead long-range effects such as breaking closed-loop inhibition.
A model of Hill-Robertson interference caused by purifying selection in a non-recombining genome
Authors: Becher Hannes , Charlesworth Brian 
Published: November 2024

AbstractA new approach to modeling the effects of Hill-Robertson interference on levels of adaptation and patterns of variability in a non-recombining genome or genomic region is described. The model assumes a set ofLdiallelic sites subject to reversible mutations between beneficial and deleterious alleles, with the same selection coefficient at each site. The assumption of reversibility allows the system to reach a stable statistical equilibrium with respect to the frequencies of deleterious mutations, in contrast to many previous models that assume irreversible mutations to deleterious alleles. The model is therefore appropriate for understanding the long-term properties of non-recombining genomes such as Y chromosomes, and is applicable to haploid genomes or to diploid genomes when there is intermediate dominance with respect to the effects of mutations on fitness. Approximations are derived for the equilibrium frequencies of deleterious mutations, the effective population size that controls the fixation probabilities of mutations at sites under selection, the nucleotide site diversity at neutral sites located within the non-recombining region, and the site frequency spectrum for segregating neutral variants. The approximations take into account the effects of linkage disequilibrium on the genetic variance at sites under selection. Comparisons with published and new computer simulation results show that the approximations are sufficiently accurate to be useful, and can provide insights into a wider range of parameter sets than is accessible by simulation. The relevance of the findings to data on non-recombining genome regions is discussed.
Convergent evolution of viral-like Borg archaeal extrachromosomal elements and giant eukaryotic viruses
Authors: Banfield Jillian F. , Valentin-Alvarado Luis E. , Shi Ling-Dong , Robinson Colin Michael , Bamert Rebecca S. , Coulibaly Fasseli , Barth Zachary K. , Aylward Frank O. , Schoelmerich Marie C , Lei Shufei , Sachdeva Rohan , Knott Gavin J. 
Published: November 2024

ABSTRACTBorgs are huge extrachromosomal elements of anaerobic methane-oxidizing archaea. They exist in exceedingly complex microbiomes, lack cultivated hosts and have few protein functional annotations, precluding their classification as plasmids, viruses or other. Here, we usedin silicostructure prediction methods to investigate potential roles for ∼10,000 Borg proteins. Prioritizing analysis of multicopy genes that could signal importance for Borg lifestyles, we uncovered highly represented de-ubiquitination-like Zn-metalloproteases that may counter host targeting of Borg proteins for proteolysis. Also prevalent are clusters of multicopy genes for production of diverse glycoconjugates that could contribute to decoration of the host cell surface, or of putative capsid proteins that we predict multimerize into hexagonal arrays. Features including megabase-scale linear genomes with inverted terminal repeats, genomic repertoires for energy metabolism, central carbon compound transformations and translation, and pervasive direct repeat regions are shared with giant viruses of eukaryotes, although analyses suggest that these parallels arose via convergent evolution. If Borgs are giant archaeal viruses they would fill the gap in the tri(um)virate of giant viruses of all three domains of life.One Sentence SummaryProtein analyses, informed byin silicoprotein structure prediction, revealed that Borgs share numerous features with giant eukaryotic viruses, suggesting that Borgs have a viral-like lifestyle and evolutionary convergence of large extrachromosomal elements across the Domains of Life.
Evolution and evolvability of rifampicin resistance across the bacterial tree of life
Authors: Bolourchi Negin , Brown Christopher R. P. , Letten Andrew D. , Engelstädter Jan 
Published: November 2024

AbstractPredicting the ability of bacteria to develop antibiotic resistance is challenging, especially for the vast majority of species for which no experimental data are available. Here, we investi-gated the evolvability and intrinsic presence of rifampicin resistance across the bacterial tree of life. We compiled a panel of known rifampicin resistance mutations, comprising 60 amino acid substitutions within the generpoB. We then screened>18 000 genomes from all major bac-terial groups for the presence of those mutations and determined which mutations can evolve through point mutations. Our results demonstrate that although the evolvability of individual mutations varies considerably across species, overall predicted evolvability is high and relatively homogeneous across bacterial taxa. Rifampicin resistance mutations are present intrinsically in 8% of species. Our analysis provides a global picture of the mutational landscape of rifampicin resistance, including both insight into existing observations as well as predictions informing future work.
GenomicSign: A computational method to discover unique, specific, and amplifiable signatures of target genomic sequences
Authors: Kumar S. Prasanna , Palaniappan Ashok 
Published: November 2024

AbstractMolecular diagnostics for the rapid identification of infectious, virulent, and pathogenic organisms are key to health and global security. Such methods rely on the identification and detection of signatures possessed by the organism. In this work, we outline a computational algorithm, GenomicSign, to determine unique and amplifiable genomic signatures of a set of target sequences against a background set of non-target sequences. The set of target sequences might comprise variants of a pathogen of interest, say SARS-CoV2 virus. Unique k-mers of the consensus target sequence for a range of k-values are determined, and the threshold k-value yielding a sharp transition in the number of unique k-mers is identified as kopt. Corresponding unique k-mers for k ≥ koptare compared against the set of non-target sequences to identifytarget-specificunique k-mers. A pair of proximal such k-mers could enclose a potential amplicon. Primers to such pairs are designed and scored using a custom scheme to rank the potential amplicons. The top-ranked resulting amplicons are candidates for unique and amplifiable genomic signatures. The entire workflow is demonstrated using a case study with the SARS-CoV2 omicron genome. A case study distinguishing the SARS-CoV2 omicron target strain against non-target other SARS-CoV2 variants is performed to illustrate the workflow. GenomicSign has been implemented in Python and is available as an open-source software under MIT licence (https://www.github.com/apalania/GenomicSign).
Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders
Authors: Gilchrist Lachlan , Mutz Julian , Hysi Pirro , Legido-Quigley Cristina , Koks Sulev , Lewis Cathryn M. , Proitsi Petroula 
Published: November 2024

AbstractEvidence indicates phenotypic and biological overlap between psychiatric and neurodegenerative disorders. Further identification of underlying mutual and unique biological mechanisms may yield novel multi-disorder and disorder-specific therapeutic targets. The metabolome represents an important domain for target identification as metabolites play critical roles in modulating a diverse range of biological processes. Here, we used Mendelian randomisation (MR) to test the causal effects of ∼1000 plasma metabolites and ∼300 metabolite ratios on anxiety, bipolar disorder, depression, schizophrenia, amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. In total, 85 causal effects involving 77 unique metabolites passed FDR correction and robust sensitivity analyses (IVW-MR OR range: 0.73-1.48;pFDR< 0.05). No evidence of reverse causality was identified. Multivariate analyses implicated sphingolipid metabolism in psychiatric disorder risk and carnitine derivatives in risk for amyotrophic lateral sclerosis and multiple sclerosis. However, polygenic risk scores for prioritised metabolites showed limited prediction in the UK Biobank. Downstream colocalisation in regions containing influential variants identified greater than suggestive evidence (PP.H4 ≥ 0.6) for a shared causal variant for 29 metabolite/psychiatric disorder trait-pairs on chromosome 11 at theFADSgene cluster. Most of these metabolites were lipids containing linoleic or arachidonic acid. Additional colocalisation was identified between the ratio of histidine-to-glutamine, glutamine, Alzheimer’s disease andSPRYD4gene expression on chromosome 12. Although no single metabolite had a causal effect on a psychiatric and a neurodegenerative disease, results suggest a broad effect of lipids across brain disorders. Metabolites identified here may help inform future targeted interventions.
A single-cell transcriptomic atlas of the prefrontal cortex across the human lifespan
Authors: Yang Hui , Clarence Tereza , Scott Madeline R. , Prashant N.M. , Wang Xinyi , Pjanic Milos , Venkatesh Sanan , Hong Aram , Casey Clara , Shao Zhiping , Alvia Marcela , Argyriou Stathis ,   PsychAD Consortium, Auluck Pavan K. , Marenco Stefano , Haroutunian Vahram , Voloudakis Georgios , Bendl Jaroslav , McClung Colleen A. , Lee Donghoon , Fullard John F. , Hoffman Gabriel E. , Girdhar Kiran , Roussos Panos 
Published: November 2024

AbstractThe dorsolateral prefrontal cortex is central to higher cognitive functions and is particularly vulnerable to age-related decline. To advance our understanding of the molecular mechanisms underlying brain development, maturation, and aging, we constructed a detailed single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, encompassing over 1.3 million nuclei from 284 postmortem samples spanning the full human lifespan (0-97 years). This atlas reveals distinct phases of transcriptomic activity: a dynamic developmental period, stabilization during midlife, and subtle yet coordinated changes in late adulthood. Modeling non-linear age trends across the lifespan shows ten distinct trajectories of the entire transcriptome from all cell types, with notable findings in neurons and microglia, linked to neurodevelopmental disorders and Alzheimer’s disease risk, respectively. Moreover, excitatory neurons exhibit a convergence of gene expression patterns across the lifespan, suggesting the emergence of a common molecular signature of aging. Pseudotime analysis tracing the progression of cellular lineages throughout life reveals key gene clusters with dynamic expression changes that reflect development, maturation, and aging, as well as their connection to brain-related diseases. We uncover significant circadian rhythm reprogramming in late adulthood, characterized by disruption of core clock gene rhythmicity and the emergence of new rhythmic patterns, particularly within microglia and oligodendrocytes. This comprehensive single-cell atlas provides a baseline for understanding the molecular transitions from development through successful aging in the human dorsolateral prefrontal cortex.
Perceptions and Misconceptions of PSA Screening in Switzerland: A Preference Epidemiology Study
Authors: Spitale Giovanni , Germani Federico , Biller-Andorno Nikola 
Published: November 2024

AbstractIntroductionPSA screening for prostate cancer detection is highly debated due to the challenging balance between its potential benefits and risks, regarding overdiagnosis and overtreatment. This study applies a preference epidemiology approach to understand how individuals evaluate these trade-offs, aiming to identify the thresholds at which people find screening acceptable or burdensome. By examining both personal and societal perspectives on PSA screening, this preference epidemiology study provides insights into how values, preferences, and psychosocial factors influence health-related decision-making.MethodsA survey of Swiss men aged 55+ examined their awareness of PSA screening, their screening history, and their willingness to participate in future screenings. Hypothetical scenarios illustrating different trade-offs between overdiagnosis and lives saved by PSA screening were presented to the participants. Data were analyzed using Chi-square tests, MANOVA, and thematic analysis.Results425 participants were included in the study. Most respondents significantly overestimated PSA screening’s life-saving potential, with a median estimate of 50 deaths prevented versus the current figure of 3 deaths prevented per 1000 persons screened reported in the literature. Over half of the participants supported the use of PSA screening even in a hypothetical scenario where no lives were saved. Personal and family cancer history were associated with increased support for PSA screening.Discussion and conclusionProviding factual information about the risks and benefits of PSA screening alone may not ensure fully informed, autonomous decision-making. A systematic understanding of how personal evaluations of the risks and benefits are conducted is essential for the assessment of screening programs, which could inform key policy decisions, such as the integration of screenings into mandatory health insurance packages. These findings highlight the importance for both policy decisions and health communication to go beyond fact-sharing and incorporate systematic evidence from nuanced, value-sensitive evaluations to better support informed and autonomous decision-making.
A Resistance Persistence Index (RPI) for antimicrobial resistance in wastewater
Authors: Hajkowski Michael , Rafael-Mingoa Benjamin , Crystal-Franco Gabriela , Dick Katherine , Acholonu Michael , Nand Sanjiev , Soto Luzmaria , Withers Brennan Nuque , Hernandez Morgan , Cheng Ariel , Anand Archana 
Published: November 2024

AbstractAntimicrobial resistance (AMR) represents a critical global health challenge, exacerbated by the proliferation of resistance genes in wastewater environments. This study introduces a novel Resistance Persistence Index (RPI) that integrates existing risk assessment frameworks with persistence and mobility metrics of antimicrobial resistance genes (ARGs) in wastewater treatment plant (WWTP) influent. We evaluated samples collected across wet and dry seasons, focusing on the dynamics of ARG diversity, abundance, and their associations with human impact. Our findings indicate a significant increase in unique ARGs during the wet season, with “antibiotic inactivation” as the predominant resistance mechanism. Using Zhang et al.’s ranking framework, we assessed the risk levels of various ARGs, revealing that while fewer high-risk ARGs were identified, they demonstrated substantial abundance. The RPI provided insights into how the combined effects of persistence and mobility influence the risk associated with different ARG families. This integrated framework offers a comprehensive tool for understanding and managing AMR in environmental settings, guiding future surveillance and intervention strategies.
Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study
Authors: Li Zexu , Ding Huitong , Wang Mengyao , Li Yi , Ang Ting Fang Alvin , Ashita Gurnani , Katherine Gifford , Karjadi Cody , Levy Daniel , Au Rhoda , Liu Chunyu 
Published: November 2024

AbstractBackgroundCognitive function measured by digital clock drawing test (dCDT) has drawn attention for their precision, automation, and reproductivity. However, the relationship between digital cognitive metrics and biological aging is lacking.MethodsWe conducted association analyses between cognitive function measured by dCDT and biological aging metrics quantified by five DNA methylation (DNAm) age metrics (Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in the Framingham Heart Study (FHS). We conducted linear regression to investigate the association between cognitive functions (global cognitive function and four sub-domain functions) and DNAm age acceleration, adjusting for covariates. We used a false discovery rate (FDR) < 0.05 for significance.ResultsAmong the 1,798 FHS participants (mean age 65±13, 53% women), we found that a lower dCDT total score is associated with DNAm age acceleration. Larger magnitudes of associations were observed in older participants (≥ 65 years). The dCDT total score showed the strongest association with the DundinPACE in the pooled sample (beta = −2.1, FDR = 0.0004), the younger (beta = −1.9, FDR = 0.02), and older age group (beta = −2.2, FDR = 0.01). The dCDT total score was significantly associated with age acceleration estimated by Horvath (beta=-1.9, FDR =0.01) and PhenoAge (beta=-2.5, FDR=0.01) in older participants while not in the pooled sample or younger participants (<65 years). In sub-domain cognitive functions, we found that simple motor function was significantly associated with DunedinPACE (FDR = 0.005) in both age groups and associated with GrimAge (FDR = 0.05 in older age group), indicating the deterioration in various organ systems may particularly impact this domain.DiscussionOur findings suggest that cognitive function measured by a digital clock drawing test is associated with DNAm age acceleration in middle-aged and older participants in the FHS, potentially shedding light on the epigenetic mechanisms underlying digitally measured cognitive function.