bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarity-weighted entropy for quantifying genetic diversity in viral quasispecies
Authors: Wu Jian 
Published: October 2024

AbstractViral quasispecies are dynamic populations of genetically diverse viruses, often exhibiting high mutation rates. Understanding the genetic diversity within these quasispecies is critical for analyzing viral evolution, adaptation, and treatment resistance. Entropy and normalized Shannon entropy are widely used metrics to quantify this diversity. However, these metrics ignore genetic similarities between sequences, potentially underestimating the true diversity. In this paper, we introduce two methods for similarity-weighted normalized entropy that account for sequence similarities and provide more accurate measures of genetic diversity. By applying these methods to two hypothetical viral quasispecies populations, we compare the traditional entropy, normalized entropy, and the proposed similarity-weighted measures. Our results demonstrate that the similarity-weighted entropies better capture the true genetic diversity in highly related viral populations, while retaining the simplicity of the original entropy calculations. We discuss the advantages and limitations of both similarity-weighted measures and propose their application in viral quasispecies studies.
Exploring associations between psychotic experiences and structural brain age: a population-based study in late adolescence
Authors: Constantinides Constantinos , Caramaschi Doretta , Zammit Stanley , Freeman Tom P , Walton Esther 
Published: October 2024

AbstractNeuroimaging studies show advanced structural “brain age” in schizophrenia and related psychotic disorders, potentially reflecting aberrant brain ageing or maturation. The extent to which altered brain age is associated with subthreshold psychotic experiences (PE) in youth remains unclear.We investigated the association between PE and brain-predicted age difference (brain-PAD) in late adolescence using a population-based sample of 117 participants with PE and 115 without PE (aged 19-21 years) from the Avon Longitudinal Study of Parents and Children. Brain-PAD was estimated using a publicly available machine learning model previously trained on a combination of region-wise T1-weighted grey-matter measures.We found little evidence for an association between PEs and brain-PAD after adjusting for age and sex (Cohen’s d = -0.21 [95% CI -0.47, 0.05], p = 0.11). While there was some evidence for lower brain-PAD in those with PEs relative to those without PEs after additionally adjusting for parental social class (Cohen’sd= -0.31 [95% CI -0.58, -0.03], p = 0.031) or birth weight (Cohen’sd= -0.29 [95% CI -0.55, -0.03], p = 0.038), adjusting for maternal education or childhood IQ did not alter the primary results.These findings do not support the notion of advanced brain age in older adolescents with PEs. However, they weakly suggest there might be a younger-looking brain in those individuals, indicative of subtle delays in structural brain maturation. Future studies with larger samples covering a wider age range and multimodal measures could further investigate brain age as a marker of psychotic experiences in youth.
Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways
Authors: Gomez Gabriela T. , Shi Liu , Fohner Alison E. , Chen Jingsha , Yang Yunju , Fornage Myriam , Duggan Michael R. , Peng Zhongsheng , Daya Gulzar N. , Tin Adrienne , Schlosser Pascal , Longstreth W.T. , Kalani Rizwan , Sharma Malveeka , Psaty Bruce M. , Nevado-Holgado Alejo J. , Buckley Noel J. , Gottesman Rebecca F. , Lutsey Pamela L. , Jack Clifford R. , Sullivan Kevin J. , Mosley Thomas , Hughes Timothy M. , Coresh Josef , Walker Keenan A. 
Published: October 2024

AbstractCerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Our proteome-wide analysis of older adults (mean age: 76) identified 13 WMH-associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis, two of which remained associated with late-life WMH volume when measured nearly 20 years earlier, during midlife. We replicated the relationship between 9 candidate proteins and WMH volume in one or more external cohorts; we found that 11 of the 13 proteins were associated with risk for future dementia; and we leveraged publicly available proteomic data from brain tissue to demonstrate that a subset of WMH-associated proteins was differentially expressed in the context of cerebral atherosclerosis, pathologically-defined Alzheimer’s disease, and cognitive decline. Bidirectional two-sample Mendelian randomization analyses examined the causal relationships between candidate proteins and WMH volume, while pathway and network analyses identified discrete biological processes (lipid/cholesterol metabolism, NF-kB signaling, hemostasis) associated with distinct forms of SVD. Finally, we synthesized these findings to identify two plasma proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), as top candidate biomarkers for elevated WMH volume and its clinical manifestations.
Low prevalence of soil transmitted helminth infection in Ugandan children hospitalized with severe malaria
Authors: Capone Drew , Jahan Nuzrath , Namazzi Ruth , Opoka Robert O. , John Chandy C. 
Published: October 2024

AbstractCo-infection by intestinal helminths andPlasmodiumspp. may be common in endemic communities. Several studies have identified a relationship between helminth infection,Plasmodiumspp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed 202 stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool and tested them for six helminth species (Anyclostoma duodenale, Ascaris lumbricoides, Necator americanus, Strongyloides stercolaris, Trichuris trichiura, Shistosoma mansoni) using highly sensitive quantitative PCR. We found a low prevalence of infection by ≥1 intestinal helminth species in children with severe malaria (5.1%, n=9/177) and community control children (4.0%, n=1/25). Infection by ≥1 of the helminths assessed was not associated with severe malaria (aRR = 1.0, 95% Confidence Interval = 0.82, 1.3, p = 0.78). In 2003 Uganda instituted a national deworming program, with anti-helminth medication provided twice annually to children 6 months to 5 years of age. In these areas of Uganda, the national deworming campaign has been highly successful, as stool-based helminth infection was rare even when using highly sensitive methods of detection and was not a major contributor to risk of severe malaria.
Multi-source coherence analysis of the first European multi-centre cohort study for cancer prevention in people experiencing homelessness: a data quality study
Authors: Blasco-Calafat Antonio , Blanes-Selva Vicent , Fragner Tobias , Doñate-Martínez Ascensión , Alhambra-Borrás Tamara , García-Gómez Juan M. , Grabovac Igor , Saez Carlos 
Published: October 2024

AbstractBackground and objectivePeople experiencing homelessness (PEH) face significant health challenges and disparities in healthcare access due to barriers such as unstable housing, limited resources, and social stigma. In response, the European Union has initiated efforts to address these disparities. The CANCERLESS project, part of this initiative, has created the first European multi-centre dataset for cancer prevention in PEH. This work aims to evaluate and describe the heterogeneity of PEH across pilot sites and to provide data quality metrics for reliable future research.MethodsThe dataset comprises 652 cases: 142 from Vienna, 158 from Athens and Thessaloniki, 197 from Madrid, and 155 from the United Kingdom. All participants fit classifications from the European Typology of Homelessness and Housing Exclusion. This longitudinal study collected questionnaires at baseline, four weeks, and at the end of the intervention. The 180-question survey covered socio-demographic data, overall health, mental health, empowerment, and interpersonal communication. Data variability was assessed using information theory and geometric methods to analyse discrepancies in distributions and completeness across the dataset.ResultsSignificant variability was found among the four pilot countries, both overall and within specific sections, except for the health section. Madrid showed the largest discrepancies, with a high number of missing values related to interpersonal communication and healthcare service use.ConclusionHealth data may be comparable across the four countries, but further analysis should account for location-specific differences. This study underscores the heterogeneity among PEH and the critical need for data quality assessments to inform future research and policymaking in this field.
Evaluating the World Health Organization’s HEARTS Model for Hypertension and Diabetes Management: A Pilot Implementation Study in Guatemala
Authors: Wellmann Irmgardt Alicia , Ayala Luis Fernando , Valley Taryn M. , Irazola Vilma , Huffman Mark D. , Heisler Michele , Rohloff Peter , Donis Rocío , Palacios Eduardo , Ramírez-Zea Manuel , Flood David 
Published: October 2024

ABSTRACTBackgroundThe World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study’s objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.MethodsWe conducted a single-arm pilot implementation trial over 6 months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary outcomes were feasibility and acceptability, measured through 20 structured interviews with Ministry of Health employees and by examining enrollment and retention. Secondary outcomes included a suite of implementation and clinical outcomes, including treatment rate.ResultsThe study enrolled 964 patients, of whom 58.8% had hypertension only, 30.4% had diabetes only, and 10.8% had both conditions. Surveys on feasibility and acceptability among Ministry of Health staff had a median score of 5.0 (IQR: 5.0 to 5.0) and 5.0 (IQR range: 4.8 to 5.0), respectively, exceeding the prespecified benchmark of ≥3.5. Both districts achieved the prespecified benchmark of enrolling ≥25 hypertension patients and ≥25 diabetes patients. Only 36% of patients attended a follow-up visit within three months, lower than the prespecified benchmark of ≥75%. M treatment rates during the pilot increased by 22.3 (95% CI: 16.2 to 28.4; P<0.001) and 3.5 (95% CI: -1.6 to 8.7; P=0.17) patients per month for hypertension and diabetes, respectively.ConclusionsImplementation of an integrated hypertension and diabetes model based on HEARTS was generally feasible and acceptable in the Ministry of Health in Guatemala. Findings can refine national scale-up in Guatemala and inform HEARTS implementation projects in other settings.
Enhancing Leptospirosis Diagnosis through an integration of Machine Learning with Classification of Microscopic Agglutination Images
Authors: Mohammad Norhasmira , Hassan Murnihayati , Zawani Rosli Siti Nur , Tahir Natasya Amirah , Mohamed Nurul Azmawati , Sukri Khairunnisa Mohd , Azmi Liyana 
Published: October 2024

AbstractLeptospirosis, a widespread zoonotic disease, poses substantial challenges to global public health. In Malaysia, leptospirosis is an endemic disease, with annual cases peaking during the monsoon season. The microscopic agglutination test (MAT) is the gold-standard serological method for confirmation of leptospirosis. However, it is labour-intensive and time-consuming, as it relies on the subjective interpretation of medical lab technicians. This study investigates and describes the development of a semi-automated workflow for leptospira screening by integrating a TensorFlow and custom-designed Keras-based Deep Convolutional Neural Network (DCNN) with conventional MAT. We used a dataset of 442 positive and 442 negative MAT images, which consisted of a mixture of leptospira serovars to train the model. We then subjected our model to hyperparameter tuning, where we adjusted various settings to optimise the model’s performance. These settings included the number of convolutional layers, filters, kernel sizes, units in dense layers, activation functions, and the learning rate. We then tailored several convolutional layers to find the optimal balance between model complexity and performance. Verification of our tested model compared to the control samples (verified patient MAT results) achieved the following metrics: a Precision score of 0.8125, a Recall of 0.9286, and an F1-Score of 0.8667. Combining our model with the current Malaysia leptospira workflow can significantly speed up, reduce inaccuracies and improve the management of leptospirosis. Furthermore, the application of this model is practical and adaptable, making it suitable for other labs that observe MAT as their leptospira diagnosis. To our knowledge, this approach is Malaysia’s first hybrid diagnostic approach for leptospira diagnosis. Scaling up the dataset would enhance the model’s accuracy, making it adaptable in other regions where leptospirosis is endemic.
Geometry-Induced Competitive Release in a Meta-Population Model of Range Expansions in Disordered Environments
Authors: Nuñez Jimmy Gonzalez , Beller Daniel A. 
Published: October 2024

AbstractRare evolutionary events, such as the rise to prominence of deleterious mutations, can have drastic impacts on the evolution of growing populations. Heterogeneous environments may reduce the influence of selection on evolutionary outcomes through various mechanisms, including pinning of genetic lineages and of the population fronts. These effects play significant roles in enabling competitive release of otherwise trapped mutations. In this work we show that environments containing random arrangements of “hotspot” patches, where locally abundant resources enhance growth rates equally for all sub-populations, give rise to massively enriched deleterious mutant clones. We derive a geometrical optics description of mutant bubbles, which result from interactions with hotspots, that successfully predicts the observed increase in mutant survival. This prediction requires no fitting parameters and holds well in scenarios of rare mutations and of adaptation from standing variation. In addition, we find that the influence of environmental noise in shaping the fate of rare mutations is maximal near a percolation transition of overlapping discs, beyond which mutant survival decreases.
Pulmonary Mitochondrial DNA Release and Activation of the cGAS-STING Pathway in LethalStx12Knockout Mice
Authors: Liu Dan-Hua , Li Fang , Yang Run-Zhou , Wu Zhuanbin , Meng Xiao-Yan , Li Sen-Miao , Li Wen-Xiu , Li Jia-Kang , Wang Dian-Dian , Wang Rui-Yu , Li Shu-Ang , Liu Pei-Pei , Kang Jian-Sheng 
Published: October 2024

AbstractSTX12 (syntaxin12 or syntaxin13), a member of the SNARE protein family, plays a crucial role in intracellular vesicle transport and membrane fusion. Our previous research has demonstrated thatStx12knockout mice exhibit perinatal lethality with iron deficiency anemia. Despite its importance, the comprehensive physiological and pathological mechanism of STX12 remain largely unknown. Here, we uncover that STX12 deficiency causes the depolarization of mitochondrial membrane potential in zebrafish embryos and mouse embryonic fibroblasts. Additionally, the loss of STX12 decreases levels of mitochondrial complex subunits, accompanying mitochondrial DNA (mtDNA) release and activating cGAS-STING pathway and Type I interferon pathway in the lung tissue ofStx12−/−mice. Additionally, we have observed a substantial increase in cytokines and neutrophil infiltration within the lung tissues ofStx12knockout mice, indicating a severe inflammation, which could be a contributing factor forStx12−/−mortality. Various interventions have failed to rescue the lethal phenotype, suggesting that systemic effects may contribute to lethality. Further research is warranted to elucidate potential intervention strategies. Overall, our findings uncover the critical role of STX12 in maintaining mitochondrial function and mtDNA stability in pulmonary cells, and reveal that STX12 depletion results in pulmonary mtDNA release and activates mtDNA-dependent innate immunity.
LRRK2-mutant microglia trigger dopaminergic neurodegeneration when activated by neuromelanin
Authors: Blasco-Agell Lucas , Pons-Espinal Meritxell , Testa Veronica , Roch Gerard , Montero-Muñoz Jara , Fernandez-Carasa Irene , Baruffi Valentina , Gonzalez-Sepulveda Marta , Richaud-Patin Yvonne , Jimenez Senda , Cuadros Thais , Cladera-Sastre Joana M. , Compte Joan , Juan-Otero Manel , Tolosa Eduardo , Raya Angel , Vila Miquel , Consiglio A. 
Published: October 2024

AbstractParkinson’s disease (PD) is a progressive and yet incurable neurodegenerative condition characterized by loss of neuromelanin-containing dopamine neurons in thesubstantia nigraof the midbrain. The contribution of non-neuronal cells to neuron degeneration in PD is receiving increasing attention. Here, we generated functional microglia-like cells from induced pluripotent stem cells (iPSC) from patients with PD associated toLRRK2mutations, the most common cause of genetic PD, along with their gene-corrected isogenic controls and with iPSC from healthy donors. Microglia-like cells of either genotype did not induce neurodegeneration of healthy dopamine neurons in co-culture experiments. However, LRRK2-mutant microglia became hyperreactive upon LPS stimulation when compared with controls, as judged by cytokine expression profile, production of reactive oxygen species. We then tested α-synuclein and neuromelanin as potential endogenous stimuli for activating mutant microglia. Upon exposure to neuromelanin-containing particles, but not to preformed α-synuclein fibrils, LRRK2-mutant microglia induced the degeneration of healthy dopamine neurons, in a process that could be prevented by pre-treatment with the immunomodulatory drug ivermectin. Finally, the analysis of post-mortem midbrain tissue of LRRK2-PD patients found increased numbers of activated microglia cells in close contact with neuromelanin-containing neurons. Taken together, our findings uncover a potential critical role of neuromelanin-activated microglia in the context of PD progression, and provide an experimental model of PD to test new therapeutic targets.
FungAMR: A comprehensive portrait of antimicrobial resistance mutations in fungi
Authors: Bédard Camille , Pageau Alicia , Fijarczyk Anna , Mendoza-Salido David , Alcañiz Alejandro J , Després Philippe C. , Durand Romain , Plante Samuel , Alexander Emilie M. M. , Rouleau François D. , Giguère Mathieu , Bernier Mégane , Sharma Jehoshua , Maroc Laetitia , Gervais Nicholas C. , Menon Anagha C.T. , Gagnon-Arsenault Isabelle , Bakker Sibbe , Rhodes Johanna , Dufresne Philippe J. , Bharat Amrita , Sellam Adnane , De Luca Domenica G. , Gerstein Aleeza , Shapiro Rebecca S. , Quijada Narciso M. , Landry Christian R. 
Published: October 2024

AbstractAntimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, we performed a thorough manual curation of published AMR mutations in fungal pathogens to produce the FungAMR reference dataset. A total of 462 papers were curated, leading to 54,666 mutation entries all classified with the degree of evidence that supports their role in resistance. FungAMR covers 92 species, 202 genes and 184 drugs. We combined variant effect predictors with FungAMR resistance mutations and showed that these tools could be used to help predict the potential impact of mutations on AMR. Additionally, a comparative analysis among species revealed a high level of convergence in the molecular basis of resistance, revealing some potentially universal resistance mutations. The analysis also showed that a significant number of resistance mutations lead to cross-resistance within antifungals of a class, as well as between classes for certain mutated genes. The acquisition of fungal resistance in the clinic and the field is an urging concern. Finally, we provide a computational tool, ChroQueTas, that leverages FungAMR to screen fungal genomes for AMR mutations. These resources are anticipated to have great utility for researchers in the fight against antifungal resistance.
Oxytocin Gαisignaling-induced amygdala astrocytes processes retraction shapes behavioral stress response
Authors: Baudon Angel , Grelot Valentin , Althammer Ferdinand , Wang Kai-Yi , Denis Clémence , Ali Syed Azmal , Yan Yudong , Castillo-Diaz Fernando , Piacentini Francesca , Creusot Etienne Clauss , Hovhannisyan Volodya , Schubert Tim , Kleinwaechter Annabel C. , Helen Jemima , Lakomy Tom , Krabichler Quirin , Breton Rachel , Derrien Pierre-Alexis , Andry Virginie , Sauvage Maria-Angeles Carrillo-de , Demais Valérie , Ces Aurélia , Kremer Mélanie , Di-Benedetto Barbara , Goumon Yannick , Schaaf Christian P. , Grinevich Valery , Rouach Nathalie , Darbon Pascal , Neumann Inga D. , Adamantidis Antoine , Busnelli Marta , Benhaim Lucile , Krijgsveld Jeroen , Pfrieger Frank W. , Charlet Alexandre 
Published: October 2024

AbstractAnticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin- dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology- dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.