bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrolysis of palm kernel meal fibre using a newly isolatedBacillus subtilisF6 with high mannanase activity
Authors: Ong Wei Li , Chan Kam Lock , Suwanto Antonius , Li Zhi , Ng Kian-Hong , Zhou Kang 
Published: June 2024

AbstractHigh fibre content is the main limitation of using mannan-rich palm kernel meal (PKM) in feeding non-ruminant livestock. Microbial fermentation stands out as a cost-effective and environmentally friendly approach for hydrolysing fibre in lignocellulosic biomass. In this study, aBacillus subtilisstrain F6 with high mannanase secretion capability was isolated from an environmental source. Fermentation of PKM using strain F6 resulted in at least a 10% reduction in its neutral detergent fibre content. Notably, the strain exhibited a rapid response to PKM, with significant mannanase activity detected as early as 6 h, enabling fibre hydrolysis within a short fermentation period. Subsequent transcriptome analysis uncovered potential enzymes involved in PKM fibre degradation, and the purified recombinant enzymes were generated to assess their activity on PKM fibre degradation. β-mannanase GmuG demonstrated strong hydrolysis activity of PKM fibre, and its biochemical properties were determined. Overall, the study reported the isolation of aB. subtilisstrain suitable for fibre hydrolysis of mannan-rich biomass, followed by an investigation to identify and characterize the enzyme responsible for fibre degradation.Graphical abstract
Individual, Household and Contextual Factors Associated with Anaemia in Children in Nigeria
Authors: Dahiru Tukur , Usman Suleiman , Hamza Khadeejah Liman , Nwankwo Bilkisu , Nmadu Awawu Grace , Lawal Aminu , Yakubu Idris Muhammad , Oyefabi Adegboyega Moses 
Published: June 2024

ABSTRACTIntroductionAnaemia among children is an issue of significant concern within the realm of public health due to its potential to result in significant adverse outcomes, including cognitive deficits and growth deficiencies. Its prevalence exhibits regional variations, wherein larger frequencies are observed in regions characterized by lower levels of socioeconomic development. This study sought to identify the individual, household, and contextual factors associated with anaemia in Nigeria.MethodsData on a weighted sample of 11,223 children under five years of age from 42,000 households was obtained from the Nigeria Demographic and Health Survey (NDHS) 2018. The study utilized the household members recode file, a data base which allows for the estimation of prevalence of childhood anaemia together with selected household variables and the kids recode file, a data base that allows for estimation of other household variables. Relevant variables were then generated, and the two data files were merged. Descriptive statistics were generated, and the multi-level logistic regression was computed to identify individual, household and contextual factors associated with anaemia.ResultsThe study found that the overall prevalence of anaemia was 67.9%. It was noted that being a: child of Muslim parents; big baby at birth; wasted, stunted; underweight, child resident in Southeast and Southwest Nigeria and a child resident in rural area were significantly associated with increased odds of anaemia. While having a mother with secondary education, being a child in the second, third, or fourth birth order belonging to richest households, living in households with tiled floors, living in households with cemented floors, living in households with carpeted floors and improved sanitation/water source and living in Northeast Nigeria were significantly associated with decreased odds of anaemia. About of 8.5% individual, household and contextual factors determine the average prevalence of anaemia in children in Nigeria.ConclusionThe findings from this study reveal that individual, household and contextual factors are important determinants of anaemia in children in Nigeria.
The MFN2 Q367H variant reveals a novel pathomechanism connected to mtDNA-mediated inflammation
Authors: Zaman Mashiat , Sharma Govinda , Almutawa Walaa , Soule Tyler GB , Sabouny Rasha , Joel Matt , Mohan Armaan , Chute Cole , Joseph Jeffrey T , Pfeffer Gerald , Shutt Timothy E. 
Published: June 2024

AbstractPathogenic variants in the mitochondrial protein MFN2 are typically associated with a peripheral neuropathy phenotype, but can also include a variety of additional pathologies including myopathy. Here, we identified a previously uncharacterized MFN2 variant, Q367H, in a patient diagnosed with late-onset distal myopathy, but without peripheral neuropathy. Consistent with the hypothesis that the Q367H MFN2 variant contributes to the patient’s pathology, patient fibroblasts and transdifferentiated myoblasts showed changes consistent with impairment of several MFN2 functions. We also observed mtDNA outside of the mitochondrial network that co-localized with early-endosomes, and measured activation of both TLR9 and cGAS-STING inflammation pathways that sense mtDNA. Notably, the inflammatory signaling was increased 3-10 fold in transdifferentiated patient myoblasts. We also found that re-expressing the Q367H variant in MFN2 knockout cells also induces mtDNA release. As elevated inflammation can cause myopathy, our findings linking the Q367H MFN2 variant with elevated TLR9 and cGAS-STING signaling that is exacerbated in myoblasts, can explain patient’s myopathy. Thus, we characterize a novel MFN2 variant in a patient with an atypical presentation that separates peripheral neuropathy and myopathy phenotypes, and establish a potential novel pathomechanism connecting MFN2 dysfunction to mtDNA-mediated inflammation.
Diametrics: A User-Friendly Web Tool for Custom Analysis of Continuous Glucose Monitoring Data
Authors: Russon Catherine , Allen Michael , Saunby Michael , Pulsford Richard , Vaughan Neil , Cocks Matthew , Low Jonathan , Hesketh Katie , Andrews Robert 
Published: June 2024

AbstractBackgroundContinuous Glucose Monitoring (CGM) systems have revolutionized diabetes management by providing real-time blood glucose tracking. However, there is a need for openly accessible tools that can analyze CGM data in relation to specific events like meals or exercise, which often require extensive technical skills to interpret, thus restricting its broader use among researchers and clinicians. Developing user-friendly web applications to facilitate this analysis could significantly broaden accessibility and utility.MethodDiametricswas built with a focus on ease-of-use and versatility. The application’s efficacy was validated againstiglu, an establishedRtool with a no-code web app for CGM analysis, using data from 418 participants from three studies. The unique period-specific analysis feature was demonstrated through an illustrative case study.ResultsDiametricsproved effective at replicated established CGM metrics, demonstrating high concordance withiglu. The platform supports a wide range of CGM devices, accommodates data in various formats, and offers extensive customization in the analysis settings. The case study highlightedDiametrics’ability to integrate exercise-related data with CGM readings, enabling detailed analyses of how different exercise types, intensities, and times of day impact glucose levels.ConclusionsDiametricsis a freely available, reproducible, user-friendly, and accurate web-based tool for CGM data analysis with a unique capability to analyze data over specific time periods. With its intuitive design and open-source accessibility,Diametricsprovides a valuable resource in diabetes research and management, empowering users of various technical levels to perform complex analyses with ease.
Integrated Clinical, Climate, and Environmental Prediction Modeling for Diagnosis of Spotted Fever Group Rickettsioses in northern Tanzania
Authors: Williams Robert J. , Brintz Ben J. , Nicholson William L. , Crump John A. , Moorthy Ganga , Maro Venace P. , Kinabo Grace D. , Ngocho James , Saganda Wilbrod , Leung Daniel T. , Rubach Matthew P. 
Published: June 2024

AbstractSpotted fever group rickettsioses (SFGR) pose a global threat as emerging zoonotic infectious diseases; however, timely and cost-effective diagnostic tools are currently limited. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, the inclusion of location-specific parameters such as climate data may improve predictive ability. To create a prediction model, we used data from 449 patients presenting to two hospitals in northern Tanzania between 2007 to 2008, of which 71 (15.8%) met criteria for acute SFGR based on ≥4-fold rise in antibody titers between acute and convalescent serum samples. We fit random forest classifiers by incorporating clinical and demographic data from hospitalized febrile participants as well as satellite-derived climate predictors from the Kilimanjaro Region. In cross- validation, a prediction model combining clinical, climate, and environmental predictors (20 predictors total) achieved a statistically non-significant increase in the area under the receiver operating characteristic curve (AUC) compared to clinical predictors alone [AUC: 0.72 (95% CI:0.57-0.86) versus AUC: 0.64 (95% CI:0.48-0.80)]. In conclusion, we derived and internally-validated a diagnostic prediction model for acute SFGR, demonstrating that the inclusion of climate variables alongside clinical variables improved model performance, though this difference was not statistically significant. Novel strategies are needed to improve the diagnosis of acute SFGR, including the identification of diagnostic biomarkers that could enhance clinical prediction models.
Impact of interventions on mpox transmission during the 2022 outbreak in Canada: a mathematical modeling study of three different cities
Authors: Xiu Fanyu , Doyle Carla , Anato Jorge Luis Flores , Knight Jesse , Wang Linwei , Cox Joseph , Grace Daniel , Hart Trevor A. , Zhang Terri , Skakoon-Sparling Shayna , Dvorakova Milada , Shahin Rita , Sachdeva Herveen , Lachowsky Nathan , Sbihi Hind , Tan Darrell H.S. , Irvine Michael A. , Mishra Sharmistha , Maheu-Giroux Mathieu 
Published: June 2024

AbstractBackgroundThe 2022-2023 global mpox outbreak primarily affected gay, bisexual, and other men who have sex with men (GBM). It was met with swift community and public health responses. The relative impact of GBM’s reductions in sexual partners, contact tracing/isolation, and vaccination on transmission in Canadian cities remain unknown.MethodsWe estimated changes in sexual behaviours during the outbreak using 2022 data from theEngage Cohort Studywhich recruited self-identified GBM in Montréal, Toronto, and Vancouver (n=1,445). The numbers of sexual partners in the past 6 months (P6M) were modeled using negative binomial regressions. A transmission-dynamic compartmental model was calibrated to surveillance data. We estimated the averted fraction of new infections attributable to reductions in sexual partners, contact tracing/isolation, and first-dose vaccination, versus an unmitigated epidemic scenario, in each of the three cities.ResultsThe empirical estimates of sexual behaviours changes were imprecise: 20% (RR=0.80; 95% credible intervals [95%CrI]: 0.47-1.36) fewer sexual partners among those reporting ≤7 partners (P6M) and 33% (RR=0.67; 95%CrI: 0.31-1.43) fewer among those with >7 partners (P6M). Compared to the unmitigated epidemics, we estimated that the three interventions combined avert 46%-58% of cases. Reductions in sexual partners, contact tracing/isolation prevented approximately 12% and 14% of cases, respectively. Vaccination’s effect varied across cities by start date and coverage, with 21%-39% mpox infections prevented.ConclusionsReduction in sexual activity, contact tracing/isolation, and vaccination all contributed to accelerating epidemic control and infections averted. Early vaccination had the largest impact.
DEVELOPMENT AND VALIDATION OF A PREDICTION RULE FOR BENEFIT AND HARM OF ORAL ANTICOAGULATION IN NON-VALVULAR ATRIAL FIBRILLATION
Authors: Raposeiras-Roubin Sergio , Chao Tze-Fan , Abu-Assi Emad , Chan Yi-Hsin , González Bermúdez Inmaculada , Liao Jo-Nan , Kuo Ling , González Ferreiro Rocío , Íñiguez-Romo Andrés 
Published: June 2024

ABSTRACTBackgroundOral anticoagulation therapy (OAC) remains the gold standard for stroke prevention in patients with atrial fibrillation (AF). In real life, there are patients who do not receive OAC due to high bleeding risk. In those patients, left atrial appendage closure (LAAC) has emerged as a potential alternative for stroke prevention. With this study, we aimed to develop a clinical decision tool to identify patients expected to derive harm vs benefit from OAC therapy.MethodsAmong 14,915 AF patients with CHA2DS2-VASc ≥ 1 (2 for women) from CardioCHUVI-AF registry (78% with OAC), a prediction rule was derived using a linear regression model to predict the stroke-bleeding balance. This rule was externally validated in the Taiwan AF registry, with 26,595 patients (70.5% with non OAC therapy).ResultsA simplified risk score was created using 7 clinical variables. The low-score group (≤ −8 points) was associated with higher rates of bleeding than stroke (7.25 vs 1.11 and 3.27 vs 2.58 per 100 patients/year in derivation and validation cohorts, respectively; p<0.001). In those patients, OAC was harmful. In contrast, high-score group (≥ +6 points) was associated with higher stroke risk than bleeding risk (2.32 vs 1.71 and 4.19 vs 1.64 per 100 patients/year in derivation and validation cohorts, respectively; p<0.001), with great benefit of OAC therapy.ConclusionsA prediction rule balancing stroke and bleeding risks correctly identify patients with harm vs benefit from OAC therapy. This rule requires further prospective evaluation to assess potential effects on patient care to select candidates for LAAC.CLINICAL PERSPECTIVEWhat is new?We developed and externally validated a simple user-friendly clinical tool -OAC score- to balance both embolic and bleeding risks in atrial fibrillation patients with CHA2DS2-VASC ≥1 (excluding female sex).According to OAC score, we can identify atrial fibrillation patients expected to derive benefit vs harm from anticoagulation therapy.Patients with a low OAC score have much higher rates of bleeding than stroke, which is exaggerated with anticoagulation. The opposite occurs in patients with a high score.What are the clinical implications?A standardised stratification of both stroke and bleeding risk in atrial fibrillation patients at high embolic risk can be performed using an user-friendly, comprehensive tool (the OAC score).In patients with low risk OAC score, despite high risk CHA2DS2-VASC, anticoagulation is not beneficial and left atrial appendage closure could be an alternative.Further studies are needed to assess the impact of oral anticoagulation and left atrial appendage closure in patients with atrial fibrillation according to the OAC score risk groups.
Connectivity profile and function of uniquely human cortical areas
Authors: Bryant Katherine L. , Camilleri Julia , Warrington Shaun , Freches Guilherme Blazquez , Sotiropoulos Stamatios N. , Jbabdi Saad , Eickhoff Simon , Mars Rogier B. 
Published: June 2024

AbstractQuantitative comparison of the white matter organization of the human neocortex with that of the chimpanzee and macaque shows a wide distribution of areas with a uniquely human connectivity profile, including the frontal-parietal fiber systems and the temporal visual pathway. Functional decoding of these areas shows their involvement in language, abstract reasoning, and social information processing. Overall, these results counter models that assign primacy to prefrontal cortex for human uniqueness.
The transcriptomic architecture of the human cerebral cortex
Authors: Nickl-Jockschat Thomas , Baek Stephen , Peterson Zeru J. , Charton Jerome , Pavic Milosch , Nastruz Meredith , Rooke Ethan , Sharkey Rachel J. , Eickhoff Simon B. , Hawrylycz Mike , Abel Ted 
Published: June 2024

SummaryFor over a century, scientists have been attempting to map the human cerebral cortex, however, they have not taken into account the complex molecular structure of the cortex, which is only beginning to be understood. Here, we parcellate the human cerebral cortex using a machine learning (ML) approach to define its transcriptomic architecture, revealing a multi-resolution organization across individuals. The transcriptomically-derived spatial patterns of gene expression separate the cortex into three major regions, frontal, temporal and parietooccipital, with smaller subregions appearing at lower levels of the transcriptomic hierarchy. The core regions, which remain stable across different hierarchical levels, are physiologically associated with language, emotion regulation, social cognition, motor and visuospatial processing and planning. Importantly, some core regions cross structural and anatomical boundaries identified in previous parcellations of the cortex, revealing that the transcriptomic architecture of the cortex is closely linked to human-specific higher cognitive function.
Optimized genome-wide CRISPR screening enables rapid engineering of growth-based phenotypes inYarrowia lipolytica
Authors: Robertson Nicholas R. , Trivedi Varun , Lupish Brian , Ramesh Adithya , Aguilar Yuna , Arteaga Anthony , Nguyen Alexander , Lee Sangcheon , Lenert-Mondou Chase , Harland-Dunaway Marcus , Jinkerson Robert , Wheeldon Ian 
Published: June 2024

AbstractCRISPR-Cas9 functional genomic screens uncover gene targets linked to various phenotypes for metabolic engineering with remarkable efficiency. However, these genome-wide screens face a number of design challenges, including variable guide RNA activity, ensuring sufficient genome coverage, and maintaining high transformation efficiencies to ensure full library representation. These challenges are prevalent in non-conventional yeast, many of which exhibit traits that are well suited to metabolic engineering and bioprocessing. To address these hurdles in the oleaginous yeastYarrowia lipolytica, we designed a compact, high-activity genome-wide sgRNA library. The library was designed using DeepGuide, a sgRNA activity prediction algorithm, and a large dataset of ∼50,000 sgRNAs with known activity. Three guides per gene enables redundant targeting of 98.8% of genes in the genome in a library of 23,900 sgRNAs. We deployed the optimized library to uncover genes essential to the tolerance of acetate, a promising alternative carbon source, and various hydrocarbons present in many waste streams. Our screens yielded several gene knockouts that improve acetate tolerance on their own and as double knockouts in media containing acetate as the sole carbon source. Analysis of the hydrocarbon screens revealed genes related to fatty acid and alkane metabolism inY. lipolytica. The optimized CRISPR gRNA library and its successful use inY. lipolyticaled to the discovery of alternative carbon source-related genes and provides a workflow for creating high-activity, compact genome-wide libraries for strain engineering.HighlightsDesigned a compact, high activity CRISPR sgRNA knockout library forYarrowia lipolytica.Developed an efficient pipeline for discovering genes involved in alternative carbon-source utilization.Identified single and double gene knockouts that improve growth on acetate.Identified genes with improved fitness and essentiality for hydrocarbon growth.
Exploring the role ofE. faecalisEnterococcal Polysaccharide Antigen (EPA) and lipoproteins in evasion of phagocytosis
Authors: Norwood Joshua S , Davis Jessica L , Salamaga Bartłomiej , Moss Charlotte E , Johnston Simon , Elks Philip M , Kiss-Toth Endre , Mesnage Stéphane 
Published: June 2024

AbstractEnterococcus faecalisis an opportunistic pathogen frequently causing nosocomial infections. The virulence of this organism is underpinned by its capacity to evade phagocytosis, allowing dissemination in the host. Immune evasion requires a surface polysaccharide produced by all enterococci, known as the Enterococcal Polysaccharide Antigen (EPA). EPA consists of a cell wall-anchored rhamnose backbone substituted by strain-specific polysaccharides called “decorations”, essential for the biological activity of this polymer. However, the structural determinants required for innate immune evasion remain unknown, partly due to a lack of suitable validated assays. Here, we describe a quantitative,in vitroassay to investigate how EPA decorations alter phagocytosis. Using theE. faecalismodel strain OG1RF, we demonstrate that a mutant with a deletion of the locus encoding EPA decorations can be used as a platform strain to express heterologous decorations, thereby providing an experimental system to investigate the inhibition of phagocytosis by strain-specific decorations. We show that the aggregation of cells lacking decorations is increasing phagocytosis and that this process does not involve the recognition of lipoproteins by macrophages. Collectively, our work provides novel insights into innate immune evasion by enterococci and paves the way for further studies to explore the structure/function relationship of EPA decorations.
Cortical synaptic vulnerabilities revealed in a α-synuclein aggregation model of Parkinson’s disease
Authors: Sah Saroj , Sauerbeck Andrew D. , Gupta Jyoti , Pérez-Acuña Dayana , Reiber Jacob E. , Russell Dreson L. , Goralski Thomas M. , Henderson Michael X. , Volpicelli-Daley Laura A. , Higley Michael J. , Kummer Terrance T. , Biederer Thomas 
Published: June 2024

AbstractCognitive impairment is a frequent non-motor symptom in Parkinson’s disease, and cortical Lewy pathology is strongly associated with cognitive decline. Synaptic pathology has been observed in the PD cortex, but the extent of synaptic vulnerabilities and their temporal and spatial relationship to pathology remains unclear. We employed high-resolution imaging to analyze synaptic abnormalities in layer 5 of the secondary motor cortex. We used striatal injections of α-synuclein pre-formed fibrils as a model to cause the progressive pathological aggregation of endogenous α-synuclein. We find that cortical α-synuclein pathology results in the progressive loss of excitatory synapses, followed by a reduction in inhibitory postsynaptic sites. Synapse loss is most pronounced in areas with high pathology. Additionally, we observed ultrastructural changes in the remaining excitatory synaptic loci, including smaller synaptic vesicles. Consistent with these results, gene ontology analysis of synaptic genes exhibiting altered expression in pathological neurons supported pre- and post-synaptic changes, including in synapse organizing pathways. Our results demonstrate that α-synuclein aggregation in the cortex is linked to molecular and structural alterations that disrupt synaptic connectivity and provide insights into the progressive PD-relevant vulnerability of cortical synapses.