bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fasting, ketogenic and anti-inflammatory diets stabilized active relapsing-remitting multiple sclerosis over 18 months – a randomized, controlled study
Authors: Bahr Lina S. , Bellmann-Strobl Judith , Koppold Daniela A. , Rust Rebekka , Schmitz-Hübsch Tanja , Olszewska Maja , Stadlbauer Jean , Bock Markus , Scheel Michael , Chien Claudia , Multmeier Jan , Krannich Alexander , Michalsen Andreas , Paul Friedemann , Mähler Anja 
Published: August 2024

AbstractBackgroundMultiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adulthood leading to disability and early retirement. Ketone-based diets improve the disease course in MS animal models and health outcomes in different pilot studies of neurodegenerative diseases.MethodsWe enrolled 105 individuals with relapsing-remitting MS (RRMS) in an 18-month, randomized, controlled study, and randomized them into 1) standard healthy diet (SD) as recommended by the German Nutrition Society, 2) fasting diet (FD) with 7-day fasts every 6 months with intermittent fasting at 6 of 7 days a week or 3) ketogenic diet (KD) with 20-40 g carbohydrates per day. Primary outcome was the number of new MRI lesions after 18 months in the KD and FD compared to SD and compared to baseline. Secondary outcomes included further MRI outcomes, disease biomarkers as well as metabolic, and clinical MS outcomes.ResultsEighty-one participants completed the study. The primary endpoint number of new T2 lesions after 18 months did not change in any of the groups (SD 0 (0-(−1)), FD 0 (2-0), KD 0 (2-0)). Compared to baseline, in the FD group, Neurofilament light chain (NfL) - concentrations were lower at 9 months (−1.94 pg/mL, p = 0.042) and depressive symptoms improved slightly at 18 months (p = 0.079). In the KD group, cognition improved at 18 months (symbol digit modalities test +3.7, p = 0.020). Cardiometabolic risk markers (body mass index, abdominal fat, blood lipids, adipokines, blood pressure) improved in all three groups at 9 months differently and were partially associated with clinical outcomes in the FD and KD group.ConclusionDietary interventions may stabilize RRMS disease course and improve cardiometabolic risk factors, cognition, and depressive symptoms, providing valuable complementary treatment options.Trial registrationClinicalTrials.gov,NCT03508414. Retrospectively registered on 25 April 2018.
Protection from Killed Whole-Cell Cholera Vaccines: A Systematic Review and Meta-Analysis
Authors: Xu Hanmeng , Tiffany Amanda , Luquero Francisco , Kanungo Suman , Bwire Godfrey , Qadri Firdausi , Garone Daniela , Ivers Louise C , Lee Elizabeth C , Malembaka Espoir Bwenge , Mendibourne Vincent , Bouhenia Malika , Breakwell Lucy , Azman Andrew S 
Published: August 2024

SummaryBackgroundKilled whole-cell oral cholera vaccines (kOCVs) are a standard prevention and control measure in cholera endemic areas, outbreaks, and humanitarian emergencies. Recently, new evidence has emerged and the ways in which the vaccines are used have changed. An updated synthesis of evidence on kOCV protection, is needed.MethodsWe systematically searched for randomized trials and observational studies that reported estimates of protection against confirmed cholera conferred by kOCVs. Eligible studies in English, French, Spanish or Chinese published through March 8, 2024, were included. Data on efficacy and effectiveness were extracted as were the number of doses, duration of follow-up, and age group. Efficacy and effectiveness estimates were summarized separately using random effects models to estimate protection by time since vaccination; meta-regression models were used to estimate protection, by dose, as a function of time since vaccination.FindingsTwenty-three publications from five randomized controlled trials and ten observational studies were included. Average two-dose efficacy one-year post-vaccination was 55% (95%CI: 46-62%), declining to 44% (95%CI: 25-59%) four years post-vaccination. Average two-dose effectiveness was 69% (95%CI: 58-78%) one-year post-vaccination declining to 47% (95%CI: 9-70%) four years post-vaccination. Only one randomized trial assessed one-dose efficacy and found sustained protection for two years (52%; 95%CI 8-75%). Average one-dose effectiveness one year after vaccination was 60% (95%CI: 51-68%) and 47% (95%CI: 34-58%) after two years. Through age-group specific meta-analysis average 2-dose efficacy in children under five years old was half that of older individuals.InterpretationTwo doses of kOCV provide protection against medically-attended cholera for at least four years post-vaccination. One-dose of kOCV provides protection for at least two years post-vaccination, but wanes faster than that of two doses. Children under five are less protected by kOCVs compared to those 5 years and older regardless of the number of doses received.FundingBill and Melinda Gates Foundation
Severe acute respiratory syndrome (SARS) mathematical models and disease parameters: a systematic review and meta-analysis
Authors: Morgenstern Christian , Rawson Thomas , Routledge Isobel , Kont Mara , Imai-Eaton Natsuko , Skarp Janetta , Doohan Patrick , McCain Kelly , Johnson Rob , Unwin H. Juliette T. , Naidoo Tristan , Dee Dominic P , Parchani Kanchan , Cracknell Daniels Bethan N , Vicco Anna , Drake Kieran O. , Christen Paula , Sheppard Richard J , Leuba Sequoia I , Hicks Joseph T , McCabe Ruth , Nash Rebecca K , Santoni Cosmo N ,   Pathogen Epidemiology Review Group, Cuomo-Dannenburg Gina , van Elsland Sabine , Bhatia Sangeeta , Cori Anne 
Published: August 2024

AbstractWe conducted a systematic review (PROSPERO CRD42023393345) of severe acute respiratory syndrome (SARS) transmission models and parameters characterising its transmission, evolution, natural history, severity, risk factors and seroprevalence. Information was extracted using a custom database and quality assessment tool.We extracted 519 parameters, 243 risk factors, and 112 models from 288 papers. Our analyses show SARS is characterised by high lethality (case fatality ratio 10.9%), transmissibility (R0range 1.1-4.59), and is prone to superspreading (20% top infectors causing up to 91% of infections). Infection risk was highest among healthcare workers and close contacts of infected individuals. Severe disease and death were associated with age and existing comorbidities. SARS’s natural history is poorly characterised, except for the incubation period and mean onset-to-hospitalisation.Our associated R package, epireview, contains this database, which can continue to be updated to maintain a living review of SARS epidemiology and models, thus providing a key resource for informing response to future coronavirus outbreaks.
α-KIDS: A novel feature evaluation in the ultrahigh-dimensional right-censored setting, with application to Head and Neck Cancer
Authors: Urmi Atika FArzana , Ke Chenlu , Bandyopadhyay Dipankar 
Published: August 2024

AbstractRecent advances in sequencing technologies have allowed collection of massive genome-wide information that substantially enhances the diagnosis and prognosis of head and neck cancer. Identifying predictive markers for survival time is crucial for devising prognostic systems, and learning the underlying molecular driver of the cancer course. In this paper, we introduceα-KIDS, a model-free feature screening procedure with false discovery rate (FDR) control for ultrahigh dimensional right-censored data, which is robust against unknown censoring mechanisms. Specifically, our two-stage procedure initially selects a set of important features with a dual screening mechanism using nonparametric reproducing-kernel-based ANOVA statistics, followed by identifying a refined set (of features) under directional FDR control through a unified knockoff procedure. The finite sample properties of our method, and its novelty (in light of existing alternatives) are evaluated via simulation studies. Furthermore, we illustrate our methodology via application to a motivating right-censored head and neck (HN) cancer survival data derived from The Cancer Genome Atlas, with further validation on a similar HN cancer data from the Gene Expression Omnibus database. The methodology can be implemented via the R package DSFDRC, available in GitHub.
Clade I Mpox virus genomic diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission
Authors: Kinganda-Lusamaki Eddy , Amuri-Aziza Adrienne , Fernandez Nicolas , Makangara-Cigolo Jean-Claude , Pratt Catherine , Hasivirwe Vakaniaki Emmanuel , Hoff Nicole A. , Luakanda Gradi , Akil-Bandali Prince , Sabiti Nundu Sabin , Mulopo-Mukanya Noella , Ngimba Michel , Modadra-Madakpa Brigitte , Diavita Ruth , Paku Princesse , Pukuta-Simbu Elisabeth , Merritt Sydney , O’Toole Áine , Low Nicola , Nkuba-Ndaye Antoine , Kavunga-Membo Hugo , Shongo Robert , Liesenborghs Laurens , Wawina-Bokalanga Tony , Vercauteren Koen , Mukadi-Bamuleka Daniel , Subissi Lorenzo , Muyembe Jean-Jacques , Kindrachuk Jason , Ayouba Ahidjo , Rambaut Andrew , Delaporte Eric , Tessema Sofonias , D’Ortenzio Eric , Rimoin Anne W. , Hensley Lisa E. , Mbala-Kingebeni Placide , Peeters Martine , Ahuka-Mundeke Steve 
Published: August 2024

ABSTRACTBackgroundRecent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC), with increasing case counts, sexual contact-mediated clusters, and sustained human-to-human transmission driven by a novel monkeypox virus (MPXV) subclade, clade Ib. However, only a limited number of clade I MPXV genomes have been characterized so far, from a limited number of regions.MethodsWe conducted whole genome sequencing of 603 mpox-positive samples that were collected from 581 patients between 2018-2024 in 17 of the 26 provinces of the DRC.ResultsGenome coverage was at least 70% for 429/603 (71.1%) samples and near full-length MPXV genomes (>90% coverage) were obtained for 348/603 (57.7%) samples from 337 patients. All newly generated MPXV sequences belonged to clade I, among which 17 were clade Ib strains, all from patients infected in 2024 in the South-Kivu province. The large majority (>95%) of the new strains fall within previously described clade Ia groups and potential new groups have also been observed. The low number of APOBEC3 mutations found among clade Ia suggests that most human mpox cases are probably linked to zoonotic transmissions. Genetically diverse MPXV lineages co-circulate in small geographic areas during the same outbreak suggesting multiple zoonotic introductions over a short period from one or multiple reservoir species. Recent identification of mpox cases in Kinshasa shows that multiple lineages circulate in a large urban center, indicating separate introduction events.ConclusionThe mpox epidemic in the DRC exhibits two distinct patterns. In traditional endemic regions, the epidemic is predominated by zoonotic spill-over events involving clade Ia. Conversely, in the eastern part of the country, the clade Ib outbreak is driven by human-to-human transmission highlighting the need for a coordinated response effort at the national, regional and international levels.
Compound screening in primary human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies
Authors: Ishii Yuki , Orr Jessica C. , El Mdawar Marie-Belle , de Pilger Denise R. Bairros , Pearce David R. , Lazarus Kyren A. , Graham Rebecca E. , Nikolić Marko Z. , Ketteler Robin , Carragher Neil O. , Janes Sam M. , Hynds Robert E. 
Published: August 2024

ABSTRACTRegeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. Basal cells are tissue-resident airway stem cells that enact regeneration, yet the mechanisms regulating their proliferation and differentiation remain incompletely understood. To identify compounds that promote primary human airway basal cell proliferation, we performed phenotype-based compound screening of 1,429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase. 16 pro-proliferative compounds validated in independent donor cell cultures, with several hit compounds activating the Wnt signalling pathway. The effects of compounds on proliferation were further explored in concentration-response, colony formation and 3D organoid assays. Structurally and functionally-related compounds that more potently induced both Wnt activation and basal cell proliferation were investigated. One such compound, 1-azakenpaullone, induced Wnt target gene activation and basal cell proliferation in mice in the absence of tracheal injury. Our results demonstrate the pro-proliferative effect of small-molecule Wnt activators on airway basal cells. These findings contribute to the rationale to develop novel approaches to modulate Wnt signalling during airway epithelial repair.Summary statementIshii, Orr and colleagues perform a high-throughput screen of 1,429 compounds in primary human airway epithelial cells, identifying Wnt activating compounds as promoters of proliferation.
Control of pili synthesis and putrescine homeostasis inEscherichia coli
Authors: Mehta Iti , Hogins Jacob , Hall Sydney , Vragel Gabrielle , Ambagaspitiye Sankalya , Zimmern Philippe , Reitzer Larry 
Published: August 2024

SummaryPolyamines are biologically ubiquitous cations that bind to nucleic acids, ribosomes, and phospholipids and, thereby, modulate numerous processes, including surface motility inEscherichia coli. We characterized the metabolic pathways that contribute to polyamine-dependent control of surface motility in the commonly used strain W3110 and the transcriptome of a mutant lacking a putrescine synthetic pathway that was required for surface motility. Genetic analysis showed that surface motility required type 1 pili, the simultaneous presence of two independent putrescine anabolic pathways, and modulation by putrescine transport and catabolism. An immunological assay for FimA—the major pili subunit, reverse transcription quantitative PCR offimA, and transmission electron microscopy confirmed that pili synthesis required putrescine. Comparative RNAseq analysis of a wild type and ΔspeBmutant which exhibits impaired pili synthesis showed that the latter had fewer transcripts for pili structural genes and forfimBwhich codes for the phase variation recombinase that orients thefimoperon promoter in the ON phase, although loss ofspeBdid not affect the promoter orientation. Results from the RNAseq analysis also suggested (a) changes in transcripts for several transcription factor genes that affectfimoperon expression, (b) compensatory mechanisms for low putrescine which implies a putrescine homeostatic network, and (c) decreased transcripts of genes for oxidative energy metabolism and iron transport which a previous genetic analysis suggests may be sufficient to account for the pili defect in putrescine synthesis mutants. We conclude that pili synthesis requires putrescine and putrescine concentration is controlled by a complex homeostatic network that includes the genes of oxidative energy metabolism.
Single-Molecule Barcoding Technology for Single-Cell Genomics
Authors: Garcia-Bassets Ivan , Mo Guoya , Xia Yu , Wu Tsai-Chin , Mekuria Immanuel , Mikhaylova Veronika , Rzepka Madison , Kawamura Tetsuya , Chang Peter L. , Paasch Amber , Pham Long , Venugopal Surya Shiv , Sanchez Sandra , de Souza Janaina S. , Yao Likun , Gu Sifeng , Bodai Zsolt , Komor Alexis C. , Muotri Alysson R. , Wang Joy , Wang Yong , Lei Ming , Almenar-Queralt Angels , Chen Zhoutao 
Published: August 2024

ABSTRACTRecent advances in barcoding technologies have significantly enhanced the scalability of single-cell genomic experiments. However, large-scale experiments are still rare due to high costs, complex logistics, and laborintensive procedures. To facilitate the routine application of the largest scalability, it is critical to simplify the production and use of barcoding reagents. Here, we introduce AmpliDrop, a technology that initiates the barcoding process using a pool of inexpensive single-copy barcodes and integrates barcode multiplicity generation with tagging of cellular content into a single reaction driven by DNA polymerase during library preparation. The barcoding reactions are compartmentalized using an electronic pipette or a robotic or standalone liquid handling system. These innovations eliminate the need for barcoded beads and complex combinatorial indexing workflows and provide flexibility for a wide range of scales and tube formats, as well as compatibility with automation. We show that AmpliDrop is capable of capturing transcriptomes and chromatin accessibility, and it can also be adapted for user-customized applications, including antibody-based protein detection, bacterial or viral DNA detection, and CRISPR perturbations without dual guide RNA-expression vectors. We validated AmpliDrop by investigating the influence of short-term static culturing on cell composition in human forebrain organoids, revealing metabolic reprogramming in lineage progenitors.
Dual quorum-sensing control of purine biosynthesis drives pathogenic fitness ofEnterococcus faecalis
Authors: Zlitni Soumaya , Bowden Sierra , Sberro Hila , Torres Marcelo D. T. , Vaughan Joan M , Pinto Antonio F M , Pinto Yishay , Fernandez Daniel , Röst Hannes , Saghatelian Alan , de la Fuente-Nunez Cesar , Bhatt Ami S. 
Published: August 2024

ABSTRACTEnterococcus faecalisis a resident of the human gut, though upon translocation to the blood or body tissues, it can be pathogenic. Here we discover and characterize two peptide-based quorum-sensing systems that transcriptionally modulate de novo purine biosynthesis inE. faecalis. Using a comparative genomic analysis, we find that most enterococcal species do not encode this system;E. moraviensis,E. haemoperoxidusandE. caccae, three species that are closely related toE. faecalis, encode one of the two systems, and onlyE. faecalisencodes both systems. We show that these systems are important for the intracellular survival ofE. faecaliswithin macrophages and for the fitness ofE. faecalisin a murine wound infection model. Taken together, we combine comparative genomics, microbiological, bacterial genetics, transcriptomics, targeted proteomics and animal model experiments to describe a paired quorum sensing mechanism that directly influences central metabolism and impacts the pathogenicity ofE. faecalis.
Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain
Authors: Zuniga Nathan R. , Earls Noah E. , Denos Ariel E. A. , Elison Jared M. , Jones Benjamin S. , Smith Ethan G. , Moran Noah G. , Brown Katie L. , Romero Gerome M. , Hyer Chad D. , Wagstaff Kimberly B. , Almughamsi Haifa M. , Transtrum Mark K. , Price John C. 
Published: August 2024

ABSTRACTApolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with the ApoE4 isoform increasing and ApoE2 isoform decreasing risk relative to the ‘wild-type control’ ApoE3 isoform. To elucidate how ApoE isoforms alter the proteome, we measured relative protein abundance and turnover in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). This data provides insight into how ApoE isoforms affect thein vivosynthesis and degradation of a wide variety of proteins. We identified 4849 proteins and tested for ApoE isoform-dependent changes in the homeostatic regulation of ∼2700 ontologies. In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3. In ApoE4 mice, this regulation is not cohesive suggesting that aerobic respiration is impacted by proteasomal and autophagic dysregulation. ApoE2 mice exhibited a matching change in mitochondrial matrix proteins and the membrane which suggests coordinated maintenance of the entire organelle. In the liver, we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues. Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology.Abstract FigureFor Table of Contents Only
ORMDL3 restrains type-I interferon signaling and anti-tumor immunity by promoting RIG-I degradation
Authors: Zeng Qi , Yao Chen , Zhang Shimeng , Mao Yizhi , Wang Jing , Wang Ziyang , Sheng Chunjie , Chen Shuai 
Published: August 2024

AbstractMounting evidence has demonstrated the genetic association of ORMDL3 (ORMDL Sphingolipid Biosynthesis Regulator 3) gene polymorphisms with bronchial asthma and a diverse set of inflammatory disorders. However, its role in type I interferon (IFN) signaling remains poorly defined. Herein, we report that ORMDL3 is a negative modulator of the type I IFN signaling by interacting with MAVS (Mitochondrial Antiviral Signaling protein) and subsequently promoting the proteasome-mediated degradation of RIG-I (Retinoic Acid-Inducible Gene I). Immunoprecipitation coupled with mass spectrometry (IP-MS) assays uncovered that ORMDL3 binds to USP10 (Ubiquitin-Specific Protease 10), which forms a complex with and stabilizes RIG-I through decreasing its K48-linked ubiquitination. ORMDL3 thus disrupts the interaction between USP10 and RIG-I, thereby promoting RIG-I degradation. Additionally, subcutaneous syngeneic tumor models in C57BL/6 mice revealed that inhibition of ORMDL3 enhances anti-tumor efficacy by augmenting the proportion of cytotoxic CD8 positive T cells and IFN production in the tumor microenvironment (TME). Collectively, our findings reveal the pivotal roles of ORMDL3 in maintaining antiviral innate immune responses and anti-tumor immunity.
A multi-model approach defines function altering MECP2 missense variants identified in individuals with autism spectrum disorder
Authors: Chen Eric , Schmitt Jessica , McIntosh Graeme , Singh Ajay , Young Barry , Lian Tianshun , Liu Jie , Khan Vedanta , Chen Ke , Liston J Beatrice , MacDonald Lily , Wang Bill , Medina Giro Sonia , Boehme Benjamin , Das Mriga , Indran Seevasant , Rogic Sanja , Pavlidis Paul , Chao Jesse T , Allan Douglas W , Loewen Christopher JR 
Published: August 2024

ABSTRACTMECP2 is commonly mutated in Rett syndrome, where MECP2’s function as a DNA cytosine methylation reader is believed critical. MECP2 variants are also catalogued in individuals with autism spectrum disorder (ASD), including nine missense variants with no known clinical significance. To assess these nine as risk alleles for ASD, we developed MECP2 variant function assays using yeast,Drosophilaand human cell lines. We calibrated these assays with known reference pathogenic and benign variants. Our data predict that four ASD variants are loss of function (LoF) and five are functional. Protein destabilization or nuclear delocalization offers insight into the altered function of a number of these variants. Notably, yeast andDrosophilalack DNA methylation, yet all Rett reference pathogenic and ASD variants in the methyl DNA binding domain that we analyzed proved to be LoF, suggesting a clinically-relevant role for non-methyl DNA-binding by MECP2.