bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prevalence, Prevention, and Treatment of Cardiovascular Diseases in Twelve African Countries (2014-2019): An Analysis of the World Health Organisation STEPwise Approach to Chronic Disease Risk Factor Surveillance
Authors: Ng’ambi Wingston Felix , Estill Janne , Merzouki Fatma Aziza , Zyambo Cosamas , Beran David , Keiser Olivia 
Published: February 2025

ABSTRACTIntroductionCardiovascular diseases (CVDs) are the most common non-communicable diseases (NCDs), responsible for more than 75% of deaths in low- and middle-income countries. We conducted this study to understand the prevalence of history of CVDs, their prevention and treatment in twelve African countries using the WHO NCDs STEPwise survey (STEPS) data.MethodsWe used secondary STEPS data from 12 African countries between 2014 and 2019. A history of heart attack, angina (chest discomfort caused by heart disease), or stroke (cerebrovascular accident or incident) was considered CVD. We fitted logistic regression models to select the predictor variables from a regression model for CVD diagnosis, CVD prevention and CVD treatment binary endpoints.ResultsAmongst 60,294 individuals, the prevalence of CVD was 5%. The CVD prevalence was higher in older individuals, females, individuals with hypertension, smokers, people with high salt intake, and in certain countries. Of the 23,630 individuals at high risk of CVD but without a history of the disease, 11% received prophylactic treatment. Amongst the 2,895 persons with CVDs, 22% received treatment or counselling for CVD: 34% receiving aspirin, 32% counselling for CVD risk factors, 11% statins, and 24% both statins and aspirin. The uptake of CVD treatment varied by hypertension status, sex, age and country.ConclusionThe prevalence of CVD was relatively low and CVD treatment uptake was sub-optimal. Concerted efforts must be made to accelerate the diagnosis and expand treatment for CVDs in Africa if to curtail untimely deaths attributable to CVDs.
An integrated DNA interactome and transcriptome profiling reveals a PU.1/enhancer RNA-mediated Feed-forward Regulatory Loop Regulating monocyte/macrophage development and innate immune functions
Authors: Waliullah A S M , Qiu Kevin , Dziegielewska Barbara , Tran Minh L. , Nguyen Nicholas N. , Wang Leran , Pan Andrew , Segovia Natalie , Umarino Simone , Zhang Junyan , Nguyen Tuan M. , Craig Jeffrey , Tenen Daniel G. , Trinh Bon Q. 
Published: February 2025

ABSTRACTHigh expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNALOUP, which we previously identified as an RNA inducer of PU.1. The genomic region within theLOUPlocus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation ofLOUPpromoter activity. Depletion ofLOUPreduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production.LOUPinduces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNALOUPare biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/LOUPregulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.
Optimisation ofRamonda serbicaLEA protein production inEscherichia coliand its secondary structure analysis
Authors: Ana Pantelić , Tatiana Ilina , Dejana Milić , Helena Gradišar , Jelena Radosavljević , Vidović Marija 
Published: February 2025

AbstractDesiccation, an extreme form of dehydration, reduces the cellular water content to below 5 % and poses a major challenge for most plants.Ramonda serbica, a tertiary relict and homoiochlorophyllous resurrection plant, is an exceptional model for investigating vegetative desiccation tolerance. Late Embryogenesis Abundant (LEA) proteins are strongly involved in this adaptive trait, but their exact molecular function is still unclear. In this study, we report the first successful recombinant production of the desiccation-induced LEA protein, RsLEAP30, from a dicotyledonous resurrection plant species using anEscherichia coliexpression system. By employing immobilised metal affinity and size-exclusion chromatography, we achieved to purify RsLEAP30 to purity over 95 %, providing a robust and scalable method for producing other LEA proteins. Structural characterisation by circular dichroism spectroscopy, combined within silicomodelling, revealed that RsLEAP30 is predominantly disordered but contains α-helical regions. We suggest that this structural duality underpins the protective role of RsLEAP30 in chloroplasts, likely via interactions with thylakoids and desiccation-sensitive proteins within photosynthesis-associated proteins. This function may be crucial for the rapid recovery of photosynthetic components upon rehydration. Our study provides new insights into the structure–function relationship of LEA proteins in resurrection plants and establishes a foundation for future investigations. Understanding the protective mechanisms of RsLEAP30 will pave the way for bioengineering strategies aimed at improving the drought tolerance of crops.
Bdnf-Ntrk2 Signaling Promotes but is not Essential for Spinal Cord Myelination in Larval Zebrafish
Authors: Russell Kristen , Kearns Christina A. , Walker Macie B. , Knoeckel Christopher S. , Ribera Angeles B. , Doll Caleb A. , Appel Bruce 
Published: February 2025

ABSTRACTMyelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.
Oculocutaneous albinism variants in 28 consanguineous families and functional classification of a pathogenic deep intron variant inTYR
Authors: Farooq Muhammad , Bruun Gitte Hoffmann , Sarusie Menachem V. K. , Kessel Line , Akhtar Hamna , Abdullah Uzma , Anjum Iram , Doktor Thomas K. , Andresen Brage Storstein , Baig Shahid Mahmood , Larsen Lars Allan , Grønskov Karen 
Published: February 2025

AbstractOculocutaneous albinism (OCA) is genetically and clinically heterogeneous recessive disorders with at least 23 associated genes. Isolated OCA is characterized by hypopigmentation in the skin, hair, and eyes combined with ocular abnormalities. Hermansky Pudlak syndrome (HPS) and Chediak-Higaski syndrome are syndromic forms of OCA, distinguished by immunological and hematological symptoms in addition to hypopigmentation and ocular anomalies. Targeted clinical care is crucial for the patients and molecular genetic diagnosis is important for classification of patients. Current diagnostic yield is approximately 70%, and a high prevalence of patients, heterozygous for pathogenic variants in OCA genes, might suggest presence of disease-causing non-coding variants.We describe here NGS analysis, including CNV analysis, of 28 consanguineous families, comprising a total of 136 individuals presenting with OCA. We provide a molecular genetic diagnosis in all 28 families. Noteworthy, five families (18 %) had pathogenic variants in a gene associated with HPS. Furthermore, we report the first deep intron variant inTYRcausing OCA and show by minigene analysis that the variant causes inclusion of a pseudoexon.
Epigenetic Regulation During Flatfish Metamorphosis: Integrative Omics Analysis of DNA Methylation and Gene Expression in Turbot Brain
Authors: Guerrero-Peña Laura , Suarez-Bregua Paula , Sánchez-Baizán Núria , Piferrer Francesc , Tena Juan J. , Rotllant Josep 
Published: February 2025

AbstractThe regulation of gene expression plays a pivotal role in the complex metamorphic process of flatfishes, which oversees the dynamic alterations that occur during their transition from a pelagic to a benthic way of life. Flatfish metamorphosis is characterized by substantial modifications in both form and function, which are initiated by thyroid hormones. Epigenetic mechanisms play a vital role in the regulation of gene expression during this transformative process. This study examines the molecular mechanisms underlying flatfish metamorphosis by integrating multi-omics data that provide information on chromatin status, DNA methylation profile, and gene expression at three key stages (pre-metamorphosis, climax and post-metamorphosis) in the turbot (Scophthalmus maximus) brain, a complex organ that plays a critical role in the regulation of this intricate process. The analysis of DNA methylation patterns revealed major epigenetic dynamic changes during the different metamorphosis stages. Specifically, the methylation levels exhibited a typical bimodal distribution in the pre-metamorphic stage, transitioned to intermediate levels of methylation (around 50%) during the climax stage, and reverted to a bimodal distribution in the post-metamorphic stage. Notably, DMRs were identified in regions of open chromatin that colocalized with CpG islands. Moreover, our results indicate an inverse relationship between DNA methylation and transcriptional activity in regions near the transcription start sites (TSSs), where high levels of methylation correspond to low expression and low levels of methylation corresponds to high gene transcription. This study thereby elucidates the regulatory impact of methylation on gene expression during the metamorphosis process in the flatfish brain.
Bioactive Flavonoid Extract Suppresses NLRP3 Activation and Inflammation in 2D and 3D Lung Models
Authors: El Sabbagh Dana El Soufi , de Souza Diulie Valente , Pappis Lauren , Davidson Carolina Bordin , Mangos Maria , Wang Aizhou , Cypel Marcelo , Attisano Liliana , Machado Alencar Kolinski , Andreazza Ana Cristina 
Published: February 2025

AbstractInflammasome activation plays a critical role in lung inflammation, with the NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) inflammasome serving as a key mediator of inflammatory cytokine release and pyroptotic cell death. This study investigates the effects of a bioactive flavonoid extract (BFE), as a potential modulator of NLRP3-mediated inflammation using THP-1 derived macrophages, A549 lung cells (2D cells), and lung organoids (3D cells). Cells were primed with lipopolysaccharide (LPS), treated with BFE, and then activated with nigericin to induce NLRP3 activation and examine BFE’s effects. Markers of inflammation, including presence of ASC specks (3D models), reactive oxygen species production (ROS) (2D models), caspase-1 activity (2D and 3D models), and IL-1β release (2D and 3D models) were measured to assess the extent of inflammasome activation in several treatment conditions. By integrating 2D and 3D lung models, this work provides insight into the NLRP3 inflammasome axis in lung inflammation and explores BFE as a potential therapeutic strategy for inflammasome-driven pulmonary inflammatory processes.
First Use of Phage Therapy in Canada for the Treatment of a Life-Threatening, Multidrug-ResistantStaphylococcus epidermidisPeriprosthetic Joint Infection: An N-of-1 Trial
Authors: Cammuso Melissa T. , Cook Bradley W. M. , Cameron D. William , Ryan Stephen , Suh Gina A. , Azad Marisa A. 
Published: February 2025

ABSTRACTWe describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistantStaphylococcus epidermidiship PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDRS. epidermidis. We developed a novel phage protocol for this patient, with twice daily, intra-articular and intravenous (7 x 109PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Ten months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.
Investigating E3 ubiquitin ligase activity of ORF150 in fish herpesvirus pathogenesis
Authors: Wang Hao , Yang Jia , Li Mengjuan , Zhang Ye , Lu Liqun 
Published: February 2025

AbstractFish herpesviruses, members of the familyAlloherpesviridae, infect aquatic species. The host’s ubiquitin-proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays a crucial role in the viral replication cycle. Viruses exploit the UPS to facilitate their replication and evade host immune responses. This study demonstrated that cyprinid herpesvirus 2 (CyHV-2) infection significantly activates the host UPS pathway, as revealed by transcriptomics sequencing analysis. Further, treatment with MG132, a proteasome inhibitor, markedly downregulates intracellular viral replication and gene transcription. Additionally, we identified a novel, highly conserved E3 ubiquitin ligase with a C3HC4-type really interesting gene (RING)-finger (RING-HC) domain, encoded by open reading frame 150 (ORF150) of CyHV-2. These findings provide critical molecular evidence that the host UPS is essential for fish herpesvirus replication and suggest that viral E3 ligases may serve as potential targets for new antiviral strategies.
Human monoclonal antibodies that target clade 2.3.4.4b H5N1 hemagglutinin
Authors: Alzua Garazi Peña , León André Nicolás , Yellin Temima , Bhavsar Disha , Loganathan Madhumathi , Bushfield Kaitlyn , Brouwer Philip J.M. , Rodriguez Alesandra J. , Jeevan Trushar , Webby Richard , Marizzi Christine , Han Julianna , Ward Andrew B. , Duty J. Andrew , Krammer Florian 
Published: February 2025

AbstractThe highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds and mammals, including infection in humans, raising concerns about its pandemic potential. We aimed to generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. H2L2 Harbour Mice®, which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007-original/2022 H5N1 virus, enabling the generation of human chimeric antibodies. Through hybridoma technology, sixteen full human mAbs were generated, most of which showed cross-reactivity against H5 proteins from different virus variants. The functionality of the sixteen mAbs was assessedin vitrousing hemagglutination inhibition and microneutralization assays with viruses containing a clade 2.3.4.4b HA. Fourteen out of the sixteen mAbs neutralized the virusin vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrated greater neutralizing capacity and showed increased protective effectsin vivowhen administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identified a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, these mAbs could serve as important treatments in case of a widespread H5N1 epidemic or pandemic.
RB-TnSeq elucidates dicarboxylic acid specific catabolism in β-proteobacteria for improved plastic monomer upcycling
Authors: Pearson Allison N. , Lynch Julie M. , Ho Cindy N. , Hudson Graham A. , Roberts Jacob B. , Menasalvas Javier , Vilchez Aaron A. , Incha Matthew R. , Schmidt Matthias , Mukhopadhyay Aindrila , Deutschbauer Adam M. , Thompson Mitchell G. , Shih Patrick M. , Keasling Jay D. 
Published: February 2025

AbstractDicarboxylic acids are key components of many polymers and plastics, making them a target for both engineered microbial degradation and sustainable bioproduction. In this study, we generated a comprehensive dataset of functional evidence for the genetic basis of dicarboxylic and fatty acid metabolism using randomly-barcoded transposon sequencing (RB-TnSeq). We identified four β-proteobacteria that displayed robust growth with dicarboxylic acid sole carbon sources and cultured their mutant libraries with dicarboxylic and fatty acids with carbon chain lengths from C3 to C12. The resulting fitness data suggested that dicarboxylic and fatty acid metabolisms are largely distinct, and different sets of β-oxidation genes are required for catabolizing dicarboxylic versus fatty acids of the same carbon chain lengths. Additionally, we identified transcriptional regulators and transporters with strong fitness phenotypes related to dicarboxylic acid utilization. InRalstonia sp.UNC404CL21Col (R. CL21), we deleted two transcriptional repressors to improve its utilization of short chain dicarboxylic acids. We exploited the diacid-utilizing catabolism ofR. CL21to upcycle a mock mixture of the dicarboxylic acids produced when polyethylene is oxidized. After introducing a heterologous indigoidine production pathway, this engineeredRastoniaproduced 0.56 ± 0.02 g/L indigoidine from a mixture of dicarboxylic acids as a carbon source, demonstrating the potential ofR. CL21to upcycle plastics waste to products derived from tricarboxylic acid (TCA) cycle intermediates.ImportanceUpcycling the carbon in plastic wastes to value-added products is a promising approach to address the plastics waste and climate crises, and dicarboxylic acid metabolism is an important facet of several approaches. Improving our understanding of the genetic basis of this metabolism has the potential to uncover new enzymes and genetic parts for engineered pathways involving dicarboxylic acids. Our dataset is the most comprehensive interrogation of dicarboxylic acid catabolism to date, and this work will be of utility to researchers interested in both plastics bioproduction and upcycling applications.
Evaluation of Metagenome Binning: Advances and Challenges
Authors: Arangasamy Yazhini , Morice Étienne , Jochheim Annika , Lieser Benjamin , Söding Johannes 
Published: February 2025

AbstractBackgroundSeveral recent deep learning methods for metagenome binning claim improvements in the recovery of high quality metagenome-assembled genomes. These methods differ in their approaches to learn the contig embeddings and to cluster them. Rapid advances in binning require rigorous benchmarking to evaluate the effectiveness of new methods. We have benchmarked newly developed state-of-the-art deep learning binners on CAMI2 datasets, including our own, McDevol.ResultsThe results show that COMEBin and GenomeFace give the best binning accuracy, although not always the best embedding accuracy. Interestingly, post-binning reassembly consistently improves the quality of low coverage bins. We find that binning coassembled contigs with multi-sample coverage is effective for low coverage dataset while binning multi-sample contigs with multi-sample coverage (‘multi-sample’) is effective for high-coverage samples. In multi-sample binning, splitting the embedding space by sample before clustering showed enhanced performance compared to the standard approach of splitting final clusters by sample.ConclusionsCOMEBin and GenomeFace emerged as the top-performing tools overall, with MetaBAT2 and GenomeFace demonstrating superior speed. To facilitate future development, we provide workflows for standardized benchmarking of metagenome binners.
Stochastic Regression and Peak Delineation with Flow Cytometry Data
Authors: Kearsley Anthony J. , Parratt Kirsten H. , Pinheiro Guilherme L. , Da Silva Sandra M. 
Published: February 2025

AbstractMany modern molecular analysis methods utilize DNA content values as part of the measurement process, and thus, the distribution of genome copies per cell within a population of cells is important. Genome copy distributions can be measured via flow cytometry by thresholding (or “gating”) a subset of cells from which estimates of the targeted properties (e.g., genome copy number) can be calculated. This manuscript introduces a new approach that gives separate estimates of signal and noise, the former of which is used for gating and analysis, and the latter is used to quantify uncertainty. In this approach stochastic regression was used to quantify subpopulations of cells that have distinctly different genome copies per cell within a heterogenous population ofEscherichia coli(E. coli)cells. By separating the signal and noise components, they can be used independently to evaluate measurement quality across different experimental conditions.