bluuebunny/crossref_metadata_2025_split huggingface dataset:
INCIDENCE AND FACTORS ASSOCIATED WITH LATE SPUTUM CULTURE CONVERSION AMONG MULTI- DRUG-RESISTANT TUBERCULOSIS PATIENTS ON TREATMENT IN NATIONAL REFERAL HOSPITAL UGANDA
Authors: Adolphus Cherop , Lydia Nakiyingi , Kalyango Joan , Katamba Achiles , Mupere Ezekiel , Emmanuel Ssendikwanawa , Bayowa Joan Rokani , Norman Cwinyaai , Ssemasaazi Amutuhaire Judith , Tom Okello , Lynn Bagoloire Kolosi , Kinya Asilaza Vincent , William Worodria 
Published: November 2024

AbstractBackgroundTuberculosis (TB) remains one of the most common causes of death from an infectious disease. Late sputum culture conversion among Multi-Drug-Resistant Tuberculosis (MDR-TB) patients poses a risk for poor treatment outcomes. The study aimed to determine the incidence and factors associated with late sputum culture conversion among MDR-TB patients on treatment at the tuberculosis (TB) unit of Mulago National Referral Hospital.MethodsA retrospective cohort study of 255 MDR-TB patient records between January 1st2012 to December 31st2018 were reviewed. Consecutive sampling was employed. Demographic characteristics, clinical factors and social factors were studied. STATA version 15 was used for analysis. Incidence was calculated as the ratio of MDR -TB patients with late sputum culture conversion result to the total number of participants studied. Factors associated were evaluated using generalized linear model (GLM) with Poisson family and log link using robust standard errors to adjust for over inflated variances.ResultsThe incidence of late sputum culture conversion was 32% (95% CI 26.3-37.8). increasing age in years (incidence rate ratio IRR 1.004, 95%CI 1.000 1.008, P value 0.044), increasing weight (IRR 0.995, 95% CI 0.991-0.999, P value 0.020) and 9-12 months multi drug tuberculosis MDR-TB regimen (IRR 0.893, 95% CI 0.805-0.989, P value 0.030) were factors associated with late sputum culture conversion.ConclusionsThe incidence of late sputum culture conversion among MDR-TB patients on treatment was high (32%), occurring in about three out of every ten patients. Increasing weight, increasing age and 9-12 months MDR-TB drug regimen were significantly associated. Isolation of patients for a minimum of two months to minimize community transmission, starting eligible patients on the 9-12months MDR-TB regimen and categorization of patients into high-risk groups (elderly and underweight) with special targeted packages.
Rare predicted loss-of-function and damaging missense variants inCFHR5associate with protection from age-related macular degeneration
Authors: Holleman Aaron M. , Deaton Aimee M. , Hoffing Rachel A. , Krohn Lynne , LoGerfo Philip , Nioi Paul , Plekan Mollie E. , Akle Serrano Sebastian , Ticau Simina , Walshe Tony E. , Borodovsky Anna , Ward Lucas D. 
Published: November 2024

ABSTRACTAge-related macular degeneration (AMD) is a leading cause of blindness among older adults worldwide, but treatment options are limited. Prior genetics studies have implicated theCFHlocus, which containsCFHand the fiveCFHR1-5genes, in AMD. While theCFHgene has been robustly linked with AMD risk, the potential additional role of the fiveCFHRgenes remains unclear, with strong linkage disequilibrium across the locus hindering the identification of individual gene contributions. Investigation of rare coding variants can help to identify causal genes in such regions. We used whole exome sequencing data from 406,952 UK Biobank participants to examine AMD associations with genes at theCFHlocus. For each gene, we used burden testing to examine the association of rare (MAF<1%) predicted loss-of-function (pLOF) and predicted-damaging missense variants with AMD. When adjusting forCFH-region variants previously established to independently associate with AMD, we find thatCFHR5rare variant burden significantly associates with decreased risk of AMD (OR=0.75, p=7×10−4), and that this association is primarily driven by pLOF variants. Furthermore, the association ofCFHR5rare variants with AMD protection is estimated as stronger for individuals carrying theCFHY402H variant, which increases AMD risk (interaction p=0.04). We also identify increased thinning of the outer segment of the photoreceptor layer of the retina to be a strong predictor of AMD and find thatCFHR5rare variant burden significantly associates with increased thickness of this retinal layer (+0.34 SD, p=4×10−4). These findings suggestCFHR5inhibition as a potential therapeutic approach for AMD.
Challenges Hindering the Translation of Plant Anticonvulsants from Bench to Bedside: A Scoping Review
Authors: Opoku Joana , Amoateng Patrick , Kukuia Kennedy Kwami Edem , Ankamah Samuel , Oppong Bekoe Emelia , Adjei Samuel , Osei-Safo Dorcas , Kombian Samuel Binamin 
Published: November 2024

ABSTRACTAimTo identify the challenges that hinder the successful translation of anticonvulsants from plant origins, from preclinical research to clinical application.DesignThis review was conducted using the Joanna Briggs Institute (JBI) guidance for a scoping review.Data SourcesThe following bibliographic databases were searched between November 11th and 20th, 2023: PubMed, Scopus, Google Scholar and ClinicalTrials.gov. The search in Google Scholar was done via a third-party application called Harzing’s Publish or Perish, where the search results limit was set at 1000 relevant articles. After full-text review, the reference lists of the included articles were examined to identify additional sources.Review MethodsThe Population, Intervention, Comparison, Outcome, Time, Setting (PICOTS) framework was employed in developing the eligibility criteria. The articles were uploaded to Rayyan.ai for title and abstract screening, as well as full-text article review. Data was extracted and synthesised from included studies using a table.ResultsThirty-seven articles met the eligibility criteria. From these articles, six distinct categories of challenges were identified: (1) methodologic issues; (2) insufficient evidence to support the use of herbal drugs in clinical settings; (3) financial disincentives; (4) challenges in obtaining natural products or its active principles; (5) poor pharmacokinetics; clinical trials and regulatory challenges.ConclusionUnderstanding and effectively addressing these challenges will ensure that more plant-based anticonvulsants are successfully translated into clinical practice, thereby enhancing the treatment of epilepsy. This review also made recommendations to tackle some of these challenges that plant anticonvulsants face in the drug development process.
Minus the Error: EstimatingdN/dSand Testing for Natural Selection in the Presence of Residual Alignment Errors
Authors: Selberg Avery G , Chikina Maria , Sackton Tim , Muse Spencer V , Lucaci Alexander G , Weaver Steven , Nekrutenko Anton , Clark Nathan , Pond Sergei L Kosakovsky 
Published: November 2024

AbstractErrors in multiple sequence alignments (MSAs) are known to bias many comparative evolutionary methods. In the context of natural selection analyses, specifically codon evolutionary models, excessive rates of false positives result. A characteristic signature of error-driven findings is unrealistically high estimates of dN/dS (e.g., >100), affecting only a small fraction (e.g., ∼0.1%) of the alignment. Despite the widespread use of codon models to assess alignment quality, their potential for error correction remains unexplored. We present BUSTED-E: a novel method designed to detect positive selection while concurrently identifying alignment errors. This method is a straightforward adaptation of the BUSTED flexible branch-site random effects model used to fit distributions of dN/dS, with an important modification: it integrates an “error-sink” component representing an abiological evolutionary regime (dN/dS > 100), and provides the option for masking errors in the MSA for downstream analyses. Statistical performance of BUSTED-E on data simulated without errors shows that there is a small loss of power, which can be mitigated by model averaged inference. Using four published empirical datasets, we show BUSTED-E reduces unrealistic rates of positive selection detection, often by an order of magnitude, and improves biological interpretability of results. BUSTED-E also detects errors that are largely distinct from other popular alignment cleaning tools (HMMCleaner and BMGE). Overall, BUSTED-E is a robust and scalable solution for improving the accuracy of evolutionary analyses in the presence of residual alignment errors, contributing to a more nuanced understanding of natural selection and adaptive evolution.
TSniffer: Unbiasedde novoidentification of RNA editing sites and quantification of editing activity in RNA-seq data
Authors: Herrmann Maike , Krebs Yvonne , Acosta Francisco M , Parusel Sebastian , Siering Oliver , Andres Felix G. M. , Taye Biruhalem , Miskey Csaba , Pfaller Christian K. 
Published: November 2024

AbstractRNA editing by adenosine deaminases acting on RNA (ADARs) is an evolutionarily conserved posttranscriptional modification essential for organismal development and normal cell function. Three catalytically active ADARs are conserved in mammals: two isoforms of ADAR1 referred to as ADAR1-p150 and ADAR1-p110, as well as ADAR2. All recognize and edit double-stranded RNA (dsRNA) structures but demonstrate target specificity and selectivity that dictate the unique essential biological functions of the three enzymes. The editing activity of ADAR1-p150 suppresses autoimmune responses against self-RNA structures, whereas ADAR1-p110 and ADAR2 have other primary functions. To better understand the mechanism of target selection by ADARs, we developedTSniffer, which allows accuratede novoidentification of edited transcripts and quantification of the extent of editing within each transcript. We found that 17-40% of protein coding transcripts in mice, ferrets, and humans are edited by ADARs. Individual transcripts can harbor hundreds and thousands of editing sites, mostly within inverted retrotransposable elements. For human transcripts, we found differential editing by ADAR1 and ADAR2, aligning with a supportive role for ADAR2, while some targets were dominantly edited by ADAR1. Relying only on RNA-seq data and reference genome,TSnifferrepresents a novel tool to decipher the role of ADAR editing in different physiological states including disease models. Its unbiased approach is suitable for any organism.
Benchmarking Peak Calling Methods for CUT&RUN
Authors: Nooranikhojasteh Amin , Tavallaee Ghazaleh , Orouji Elias 
Published: November 2024

AbstractCleavage Under Targets and Release Using Nuclease (CUT&RUN) has rapidly gained prominence as an effective approach for mapping protein-DNA interactions, especially histone modifications, offering substantial improvements over conventional chromatin immunoprecipitation sequencing (ChIP-seq). However, the effectiveness of this technique is contingent upon accurate peak identification, necessitating the use of optimal peak calling methods tailored to the unique characteristics of CUT&RUN data. Here, we benchmark four prominent peak calling tools, MACS2, SEACR, GoPeaks, and LanceOtron, evaluating their performance in identifying peaks from CUT&RUN datasets. Our analysis utilizes in-house data of three histone marks (H3K4me3, H3K27ac, and H3K27me3) from mouse brain tissue, as well as samples from the 4D Nucleome database. We systematically assess these tools based on parameters such as the number of peaks called, peak length distribution, signal enrichment, and reproducibility across biological replicates. Our findings reveal substantial variability in peak calling efficacy, with each method demonstrating distinct strengths in sensitivity, precision, and applicability depending on the histone mark in question. These insights provide a comprehensive evaluation that will assist in selecting the most suitable peak caller for high-confidence identification of regions of interest in CUT&RUN experiments, ultimately enhancing the study of chromatin dynamics and transcriptional regulation.
Development of a Tick-Borne Encephalitis Virus Nanoparticle Vaccine Utilizing Envelope Dimer
Authors: Wang Bingjie , Zhao Haiyan 
Published: November 2024

ABSTRACTTick-borne encephalitis virus (TBEV) is primarily transmitted to humans through tick bites, leading to symptoms of encephalitis with a fatality rate ranging from 1% to 30%, depending on the virus subtype. Currently, only inactivated virus vaccines are available for human use, though break-through infections can still occur. Therefore, developing new vaccines against TBEV is crucial. In this study, we designed and characterized a novel nanoparticle-based TBEV envelope (E) dimer vaccine. We successfully expressed and purified the TBEV E dimer by engineering disulfide bond mutants, and animal experiments demonstrated that the E dimer protein elicited a stronger immunogenic responses compared to the E monomer protein. Further, antibody depletion experiment confirmed that the E dimer protein effectively mimics the virion surface structure, inducing robust humoral immunity targeted at neutralizing epitopes. We also presented the TBEV E dimer on the surface of the nanoparticle Mi3 using the SpyCatcher-SpyTag system, with animal experiment showing that this TBEV E dimer nanoparticle vaccine elicited a potent humoral immune response. These findings offer new insights into the immunogenicity of the TBEV E dimer and suggest that the nanoparticle-based TBEV E dimer vaccine represents a promising and highly effective candidate for TBEV immunization.
Should elephants graze or browse? The nutritional and functional consequences of dietary variation in a mixed-feeding megaherbivore
Authors: Gautam Hansraj , Berzaghi Fabio , Thanikodi M , Ravichandran Abhirami , Sreeman Sheshshayee M. , Sankaran Mahesh 
Published: November 2024

ABSTRACTUnlike specialist browsers and grazers, the diets of mixed-feeding megaherbivores like elephants are complex and broad, comprising numerous plant species of variable nutritional quality. Here, we revisit an unresolved debate on whether browse is more nutritious than grasses for elephants, as browse is thought to have greater crude protein content. We first analyzed carbon isotopes in 102 fecal samples of Asian elephants to quantify the contribution of browsing and grazing to their diet in Nagarahole National Park, southern India. We show that elephants are predominantly browsers in the grass-scarce Nagarahole forests, in contrast with predominant grazing reported in the nearby grass-abundant savannas of the Nilgiri Biosphere Reserve. We then compared the forage quality of high-browsing and high-grazing diets by analyzing these samples for two proxies of crude protein content (CP): nitrogen content (N%) and Carbon-to-Nitrogen ratio (C:N). Interestingly, high-browsing diets did not have higher N% or lower C:N (proxies for high CP) than low-browsing (high-grazing) diets. To explore the generality of this finding, we analyzed nutritional differences (i.e., CP and fibre content values) between browse and grass across 141 plant species consumed by Asian elephants. We show that woody browse and non-legume browse, which are major components of elephant browse, do not have appreciably higher CP than grasses. Our findings suggest that browsing and grazing broadly have similar nutritional value for such bulk-feeding mixed feeders. Finally, based on the observed habitat-wide variation in browsing, we provide a new framework for assessing how elephants shape woody vegetation across the forests and savannas of Asia, with important implications for conservation and carbon cycling.
Unbiased discovery of antibody therapies that stimulate macrophage-mediated destruction of B-cell lymphoma
Authors: Ribeiro Juliano , Pagès-Geli Carlota , Meglan Anna , Velarde Jose , Blandin Jasmine , Vaccaro Kyle , Wienclaw Thomas , Fernández-Guzmán Patricia , Hahn Cynthia K. , Crespo Marta , Weiskopf Kipp 
Published: November 2024

AbstractMacrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells. Across both mouse and human systems, we identified multiple unappreciated targets of opsonization as well as putative immune checkpoints. We used this information to engineer a compendium of 156 bispecific antibodies, and we identified dozens of bispecifics that dramatically stimulate macrophage-mediated cytotoxicity of lymphoma cells. Among these, a bispecific comprising a SIRPα decoy domain and a CD38-targeting arm (WTa2d1xCD38) exhibited maximal efficacy while minimizing the risk of hematologic toxicity. This bispecific stimulated robust anti-tumor responses in multiple xenograft models of aggressive B-cell lymphoma. Our approach can be directly applied to other cancers to rapidly discover bispecific antibodies that leverage anti-tumor responses by macrophages or other innate immune cells.
High fitness paths can connect proteins with low sequence overlap
Authors: Kantroo Pranav , Wagner Günter P. , Machta Benjamin B. 
Published: November 2024

AbstractThe structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein’s sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral networks can connect a local region of sequence space by single residue mutations that preserve viability. However, the larger-scale connectedness of protein morphospace remains poorly understood. Recent advances in artificial intelligence have enabled us to computationally predict a protein’s structure and quantify its functional plausibility. Here we build on these tools to develop an algorithm that generates viable paths between distantly related extant protein pairs. The intermediate sequences in these paths differ by single residue changes over subsequent steps – substitutions, insertions and deletions are admissible moves. Their fitness is evaluated using the protein language model ESM2, and maintained as high as possible subject to the constraints of the traversal. We document the qualitative variation across paths generated between progressively divergent protein pairs, some of which do not even acquire the same structural fold. The ease of interpolating between two sequences could be used as a proxy for the likelihood of homology between them.
Epigenetic modulation of NLRP6 inflammasome sensor as a therapeutic modality to reduce necroptosis-driven gastrointestinal mucosal dysfunction in HIV/SIV infection
Authors: Premadasa Lakmini S. , McDew-White Marina , Romero Luis , Gondo Beverly , Drawec Jade A. , Ling Binhua , Okeoma Chioma M. , Mohan Mahesh 
Published: November 2024

AbstractThe epigenetic mechanisms driving persistent gastrointestinal mucosal dysfunction in HIV/SIV infection is an understudied topic. Using reduced-representation bisulfite sequencing, we identified HIV/SIV infection in combination anti-retroviral therapy (cART)-naive rhesus macaques (RMs) to induce marked hypomethylation throughout promoter-associated CpG islands (paCGIs) in genes related to inflammatory response (NLRP6, cGAS), cellular adhesion and proliferation in colonic epithelial cells (CEs). Moreover, low-dose delta-9-tetrahydrocannabinol (THC) administration reduced NLRP6 protein expression in CE by hypermethylating theNLRP6paCGI and blocked polyI:C induced NLRP6 upregulation in vitro. In cART suppressed SIV-infected RMs, NLRP6 protein upregulation associated with significantly increased expression of necroptosis-driving proteins; phosphorylated-RIPK3(Ser199), phosphorylated-MLKL(Thr357/Ser358), and HMGB1. Most strikingly, supplementing cART with THC effectively reduced NLRP6 and necroptosis-driving protein expression to pre-infection levels. These findings for the first time demonstrate that NLRP6 upregulation and ensuing activation of necroptosis promote HIV/SIV-induced gastrointestinal mucosal dysfunction and that epigenetic modulation using phytocannabinoids represents a feasible therapeutic modality for alleviating HIV/SIV-induced gastrointestinal inflammation and associated comorbidities.
Comprehensive Mosquito Wing Image Repository for Advancing Research on Geometric Morphometric- and AI-Based Identification
Authors: Nolte Kristopher , Agboli Eric , Azambuja Garcia Gabriela , Badolo Athanase , Becker Norbert , Loc Do Huy , Dworrak Tarja Viviane , Eguchi Jacqueline , Eisenbarth Albert , de Freitas Rafael Maciel , Doumna-Ndalembouly Ange Gatien , Heitmann Anna , Jansen Stephanie , Jöst Artur , Jöst Hanna , Kiel Ellen , Meyer Alexandra , Pfitzner Wolf-Peter , Saathoff Joy , Schmidt-Chanasit Jonas , Sulesco Tatiana , Tokatlian Artin , Velavan Thirumalaisamy P. , de Castro Carmen Villacañas , Wehmeyer Magdalena Laura , Zahouli Julien , Sauer Felix Gregor , Lühken Renke 
Published: November 2024

AbstractAccurate identification of mosquito species is essential for effective vector control and mitigation of mosquito-borne disease outbreaks. Traditional morphological identification requires highly specialized personnel and is time-consuming, while molecular techniques can be cost-effective and dependent on comprehensive genetic information. Wing geometric morphometry has emerged as a promising alternative, leveraging detailed geometric measurements of wing shapes and vein patterns to distinguish between species and detect intraspecies variations. This paper presents a curated dataset of 18,104 mosquito wing images, collected from 10,500 mosquito specimens, annotated with extensive meta-information, designed to support research in wing geometric morphometry and the development of machine learning models, ultimately supporting efforts in vector surveillance and research.