bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global, Regional, and National Burden of Pulmonary Arterial Hypertension, 1990-2021: a Systematic Analysis of the Global Burden of Disease Study 2021
Authors: Deng Yafang , Dong Xingbei , Qian Junyan , Zhao Jiuliang , Xu Dong , Wang Yanhong , Li Mengtao , Zeng Xiaofeng , Wang Qian 
Published: October 2024

AbstractAimsPulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease with high mortality rates. This research aimed to examine the disease burden of PAH including prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 across various age groups, sexes, and Socio-demographic Index (SDI) levels, at global, regional and national levels.MethodsData was collected from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2021, which established models to estimate the burden of PAH for 204 countries and territories from 1990 to 2021. Age-standardized rates for PAH prevalence, incidence, mortality, and DALYs were calculated. Joinpoint regression was used to assess temporal trends. The correlation between disease burden and socioeconomic development was analyzed.ResultsIn 2021, the global age-standardized prevalence and incidence rates were 2.28 and 0.52 per 100,000 population, respectively. From 1990 to 2021, the age-standardized mortality rate decreased from 0.35 to 0.27 per 100,000, with an average annual trend of -0.82%. TheCorresponding AuthorDr. Qian Wang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, No. 1, Shuaifuyuan, Wangfujing Ave, Dongcheng District, Beijing 100730, China E-Mail:wangqian_pumch@126.comage-standardized DALY rate decreased from 13.21 to 8.24 per 100,000 by -1.52%. Females exhibited a higher incidence rate but lower mortality and DALY rates. The burden of PAH distributed unequally, with regions possessing higher socioeconomic statuses exhibiting lower mortality and DALY rates. Such inequalities have been improved over past decades.ConclusionsThe decline in mortality and DALY rates of PAH indicates improvements in disease management and patient outcomes, while the health inequalities among different regions and countries persist. Improving survival and life quality, and global health equality are crucial for future progress.
Multiplex ACE2-RBD Binding Inhibition Assay: An Integrated Tool for Assessing Neutralizing Antibodies to SARS-CoV-2 Variants and Protection against Breakthrough Infections
Authors: Bloch Emma , Garcia Laura , Donnadieu Françoise , Rosado Jason , Planas Delphine , Bruel Timothée , Hocqueloux Laurent , Prazuck Thierry , Schwartz Olivier , Tondeur Laura , Pinaud Laurie , Fontanet Arnaud , Pelleau Stéphane , White Michael 
Published: October 2024

AbstractSARS-CoV-2 remains a significant health threat due to its high infection and mutation rates. The emergence of new variants of concern poses challenges as they can lead to immune escape mutations, potentially reducing the efficacy of vaccines and antibody therapeutics. The receptor binding domain (RBD) of SARS-CoV-2 is particularly noteworthy as it is both the most rapidly evolving domain and the principal target of neutralizing antibodies. As an alternative to time-consuming and expensive neutralization assays, we have developed a bead-based multiplex surrogate virus neutralization test based on ACE2-RBD binding inhibition. We demonstrated how our high-throughput assay allows us to simultaneously assess anti-RBD neutralizing antibodies levels against multiple SARS-CoV-2 variants, providing data that is consistent with the gold-standard live virus neutralization assay. The utility of this assay was demonstrated by applying it to a large French population cohort to demonstrate that hybrid immunity (generated by a combination of vaccination and infection) is associated with protection against infection with the Omicron BA.1 and BA.2 lineages of SARS-COV-2.
Comparison of Oscillometry with Lung Function Parameters between Bronchial Asthma with Airflow Obstruction and COPD Patients
Authors: De Sajal , Sarda Aakansha Ashok 
Published: October 2024

BackgroundLung oscillometry is an emerging lung function test for assessing obstructive airway disease. Comparisons of oscillometry parameters and their bronchodilator responsiveness (BDR) between bronchial asthma and chronic obstructive pulmonary disease (COPD) patients are limited.Research QuestionDo oscillometry parameters and their BDR differ between stable asthma and COPD patients with similar severity of airflow obstruction?Study Design and MethodsWe included 467 consecutive adult patients with a clinical history of asthma (n=187) or COPD (n=280). Oscillometry, spirometry, and body plethysmography were performed before and after inhaling 400 μg of salbutamol. Patients were stratified based on the severity of airflow obstruction in spirometry. The z scores of the oscillometry parameters were used for the comparison. The BDR of oscillometry parameters with other lung function parameters was also compared.ResultsThe average age of the study population was 54.9 years, and 76.4% were male. COPD patients were older, had a greater number of smokers, and had poorer lung function. The magnitude of oscillometry parameters worsened with increasing severity of airflow obstruction, regardless of the underlying disease. Asthma patients, particularly those with moderate and severe airway obstruction, had significantly higher R5 and R19 than COPD patients. The within- and whole-breath X5 of asthma were not different from those of COPD patients with similar severities of airflow obstruction. Expiratory flow limitation at tidal breaths (ΔX5 > 0.28 kPa/L/s) was observed in both asthma and COPD patients across all severities of airflow obstruction. The proportion of BDR in oscillometry was significantly lower than that in spirometry for both asthma (35.3% vs. 57.1%; p<0.01) and COPD patients (19.3% vs. 47.1%; p=0.02).InterpretationOscillometry parameters except for R5 and R19 did not differ between asthma and COPD patients with similar severities of airflow obstruction. Similar to spirometry, COPD patients had lower BDR in oscillometry than asthma patients.Take-home PointsStudy QuestionAre oscillometry parameters and their bronchodilator responsiveness different between bronchial asthma and COPD patients with similar severities of airflow obstruction?ResultsWe compared the FOT between 187 bronchial asthma and 280 COPD patients. Except for R5 and R19, the severity and distribution of high oscillometry parameters did not differ between asthma and COPD patients.InterpretationThe severity of oscillometry abnormalities is primarily determined by the severity of airflow obstruction, not the underlying disease.
Treatment of obesity in US children and adolescents before and after the AAP guidelines
Authors: Rodriguez Patricia J , Do Duy , Gratzl Samuel , Cartwright Brianna M Goodwin , Stucky Nicholas L , Wright R. Davene 
Published: October 2024

AbstractImportanceThe American Academy of Pediatrics (AAP) published new comprehensive guidelines for childhood obesity treatment, including pharmacotherapy. However, changes in treatment patterns following these guidelines remain unknown.ObjectiveTo assess changes in childhood and adolescent obesity treatment following the new AAP guidelines.DesignUsing Truveta electronic health record (EHR) data, this cohort study analyzed outpatient visits between January 2021 and June 2024 for children (age 8-11) and adolescents (age 12-17) with obesity and no evidence of type 2 diabetes (T2D). For patients with multiple visits, one visit was randomly selected. Patients without a recent history of specific obesity treatments were followed for evidence of obesity treatment at or following their visit, including nutrition referral within 14 days or nutrition counseling within 90 days, and, separately, pharmacotherapy prescriptions for weight management (on- or off-label) within 14 days. Interrupted time series models were used to compare differences in nutrition counseling or referral and pharmacotherapy before versus after the AAP guidelines were released.SettingClinical and prescribing data from EHRs from a collective of US health systems.Participants329,357 patients aged 8 to 17 with an outpatient office visit, a BMI percentile indicating obesity, and no T2D diagnosis.ExposureRelease of the AAP guidelines in January 2023.Main Outcomes and MeasuresEvidence of obesity treatment at or following the eligible visit with (1) nutrition referral or counseling, and (2) pharmacotherapy.ResultsThe study population of 329,581 patients included 120,734 (36.6%) children and 208,847 (63.4%) adolescents. The mean (SD) BMI percentile was 97.4 (1.6), with 119,864 (36.4%) having severe obesity (class 2 or 3). Overall, a minority of patients without a recent history of obesity treatment had evidence of nutrition referral or counseling (4.0%) or pharmacotherapy (0.4%) during or shortly after their visit. Following the AAP guidelines, indicators of both immediate (odds ratio [95% CI]: 1.38 [1.08-1.75]) and gradual monthly changes (1.06 [1.04-1.08]) were observed for pharmacotherapy use. An immediate change in nutrition counseling and referral was observed following guidelines (1.34 [1.24-1.45]), but no additional gradual monthly changes were observed (1.0 [0.99-1.01]).Conclusions and RelevanceWhile nutrition counseling or referral and pharmacotherapy use increased, overall rates of obesity treatment remained low.
Patterns and predictors of COVID-19 vaccine uptake among United States active duty Service members, 2020-2022: Implications for future pandemics
Authors: Sercy Erica , Stewart Laveta , Craig-Kuhn Megan Clare , Stern Caryn , Graham Brock , Michel Amber , Parmelee Edward , Pollett Simon , Burgess Timothy , Tribble David R 
Published: October 2024

AbstractIntroductionVaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the United States Department of Defense issued a COVID-19 vaccine mandate for all ADSMs. This study aimed to investigate COVID-19 vaccine uptake among the ADSM population, as well as factors associated with timing of COVID-19 vaccine receipt.MethodsThis study included ADSMs on active duty between 1/1/2020-6/30/2022. Univariate analyses investigated associations between demographic factors (age, sex, race, ethnicity, branch of service, rank, state of residence) and COVID-19 diagnosis with the following outcomes: 1) time to primary series initiation in relation to the DoD vaccine mandate, 2) time between doses of the two-dose primary series, and 3) time between booster eligibility and receiptResultsA total of 1,799,466 ADSMs were included, with 90% receiving ≥1 COVID-19 vaccine dose during the study period and 77% initiating the primary series prior to the mandate. Over 80% of ADSMs received a complete primary series, with 96% of those adhering to the recommended regimen. History of COVID-19 diagnosis was associated with later receipt of all doses.ConclusionsCOVID-19 vaccine uptake was high among all ADSMs, with the majority initiating the primary series before the mandate. The high vaccine uptake among ADSMs shown here may be used as a guide to both military and civilian pandemic policy and outreach efforts related to enhanced vaccine uptake.
Long-term hybridization in a karst window reveals the genetic basis of eye loss in cavefish
Authors: Kellermeyer Riley , Seidel Chris , Redwine William B. , Moran Rachel L. , Bertho Sylvain , Ornelas-García Claudia Patricia , Alegre Dana , Weaver Kyle , Unruh Jay , Troutwine Benjamin , Wang Yongfu , Collins Emily , Rutkowski Jennifer , McGaugh Suzanne E. , Espinasa Luis , Rohner Nicolas 
Published: October 2024

AbstractEye loss is a hallmark trait of animals inhabiting perpetual darkness, such as caves. The Mexican tetra (Astyanax mexicanus)provides an unparalleled model for studying the genetic basis of eye loss. There are two interfertile morphs of the Mexican tetra, sighted surface fish and multiple independently evolved eyeless, blind cavefish populations. Despite decades of research on eye loss in this species, our understanding of the precise genetic basis remains sparse. Here, we focused on the unique Caballo Moro cave, where there is a karst window collapse that introduced sunlight and coexistence of both eyed and eyeless cavefish of similar genetic background. This unique genetic mosaic allowed us to pinpoint coding mutations in Connexin 50 (Cx50), also known as gap junction protein alpha 8b (Gja8b), as critical in the genetic basis of eye loss. CRISPR based knockouts of Cx50 in surface fish result in small or absent eyes as young as 48 hours post-fertilization. Further, we identified similar mutations in Cx50 that alter predicted protein structure among other cave-dwelling fish and even subterranean mammals, indicating a conserved evolutionary mechanism of Cx50 mutations. We introduced a mutation (Cx50-S89K) in mice, which resulted in cataracts, smaller eyes, and smaller lenses. Mutations in Cx50 mimic those identified in human congenital cataracts. We additionally leveraged phenotypic variation in a hybrid cavefish population to demonstrate that eyes provide fish with a metabolic advantage, providing a mechanism by which loss of eyes could be favored by selection. This unique hybridization event allowed us to identify novel alleles that contribute to the convergent evolution of eye loss, providing profound insights into the genetic underpinnings of one of nature’s most fascinating adaptive traits.
A head-to-head comparison of plasma biomarkers to detect biologically defined Alzheimer in a memory clinic
Authors: Anastasi Federica , Fernández-Lebrero Aida , Ashton Nicholas J. , Ortiz-Romero Paula , Torres-Torronteras Javier , González-Escalante Armand , Milà-Alomà Marta , Contador José , García-Escobar Greta , Manero-Borràs Rosa María , Navalpotro-Gómez Irene , Sahajan Aparna , Hao Qinyu , Zhang Bingqing , Jeromin Andreas , Le Bastard Nathalie , Nadal Alicia , Mousavi Tahmine , Kollmorgen Gwendlyn , Carboni Margherita , Grau-Rivera Oriol , Zetterberg Henrik , del Campo Marta , Blennow Kaj , Puig-Pijoan Albert , Suárez-Calvet Marc 
Published: October 2024

ABSTRACTINTRODUCTIONBlood-based biomarkers for Alzheimer’s disease (AD) have been widely studied, but direct comparisons of several biomarkers in clinical settings remain limited.METHODSIn this cross-sectional study, plasma biomarkers from 197 participants in the BIODEGMAR cohort at Hospital del Mar (Barcelona) were analysed. Participants were classified based on AD cerebrospinal fluid (CSF) core biomarkers. We assessed the ability of plasma p-tau181, p-tau217, p-tau231, t-tau, and Aβ42/40 to classify Aβ status.RESULTSPlasma p-tau biomarkers had a greater diagnostic performance and larger effect sizes compared to t-tau and Aβ42/40 assays in detecting biologically defined AD. Among them, plasma p-tau217 consistently outperformed the others, demonstrating superior AUC. Furthermore, p-tau217 showed the strongest correlation between plasma and CSF levels, underscoring its potential as a reliable surrogate for CSF biomarkers.DISCUSSIONSeveral plasma biomarkers, targeting different epitopes and using different platforms, demonstrated high performance in distinguishing biologically defined AD in a memory clinic setting.
Altered resting state EEG microstate dynamics in acute-phase pediatric mild traumatic brain injury.
Authors: Sattari Sahar , Damji Samir , McLeod Julianne , Mirian Maryam M. , Wu Lyndia , Virji-Babul Naznin 
Published: October 2024

Objective: Sport-related concussion presents significant diagnostic and monitoring challenges, especially in youth populations. This study investigates the potential of EEG microstate analysis as a tool for assessing acute-phase brain activity changes in adolescent male athletes following a concussion. We analyzed resting-state EEG data from 32 participants in a between-subjects design, comparing participants with acute concussion (within two weeks of injury) to an age- and sex- matched sample with no reported history of concussion. Methodology: We applied a modified k-means clustering algorithm to group resting-state EEG topographical maps into seven clusters, with each cluster represented by one of the canonical microstate classes (A-G). Average duration, occurrence rate, and time coverage for each microstate were extracted. Results: Statistically significant differences in mean duration, occurrence rate, and time coverage of microstates B and E were observed. Specifically, the mean duration, occurrence and time coverage of microstate E showed a significant decrease in the concussed cohort in comparision to the controls (p < 0.001). In addition, the mean duration, occurrence rate and time coverage was higher in the concussed cohort in comparision with the healthy cohort (p = 0.003). A significant negative linear relationship was found between microstate E and symptom severity (p = 0.006, F = 15.72). Discussion: These results suggest that mild traumatic brain injury may disrupt the dynamic interaction of large-scale brain networks, hinting at potential biomarkers of injury. This study may help to inform future work on objective, brain-based tools for diagnosis and recovery assessment in concussed adolescents. Further research in larger, more diverse populations is necessary to validate these potential biomarkers.
Muscle-3D: scalable multiple protein structure alignment
Authors: Edgar Robert C. , Tolstoy Igor 
Published: October 2024

ABSTRACTProtein multiple alignment is an essential step in many bioinformatics analysis such as phylogenetic tree estimation, HMM construction and critical residue identification. Structure is conserved between distantly-related proteins where amino acid similarity is weak or undetectable, suggesting that structure-informed sequence alignments might offer advantages over alignments constructed from amino acid sequences alone. The advent of the AI folding era has unleashed millions of high-quality predicted structures, motivating the development and assessment of scalable multiple structure alignment (MStA) methods. Here, we describe Muscle-3D, a new MStA algorithm combining a rich sequence representation of structure context, the Reseek “mega-alphabet”, with state-of-the art alignment techniques from Muscle5 including a posterior decoding pair-HMM, consistency transformation, iterative refinement and ensemble construction. We show that Muscle-3D readily scales to thousands of structures. Comparative validation on several benchmark datasets using different quality metrics shows Muscle-3D to be among the higher-scoring methods, but we find that algorithm rankings from different metrics disagree despite low P-values according to the Wilcoxon rank-sum test. We suggest that these conflicts arise from the inherently fuzzy nature of structural alignment, and argue that a universal standard of MStA accuracy is not possible in principle. We describe contact map profiles for visualizing variation in inter-residue distances, and introduce a novel measure of local conformation similarity, LDDT-muw.Muscle-3D software is available athttps://github.com/rcedgar/muscle.
Identification of Molecular Compounds Targeting Bacterial Propionate Metabolism with Topological Machine Learning
Authors: Tola Astrit , Aziz Shan , Zhabilov Dannie , Winkler Duane , Coskunuzer Baris , Candas Mehmet 
Published: October 2024

AbstractThis study demonstrates the effective integration of comparative protein sequence analysis with novel topological machine learning methods to tackle a key issue in computational biology: identifying potential inhibitor compounds for methylcitrate dehydratase—an enzyme essential to the methylcitrate pathway in bacteria and fungi. While many ML models have proven effective on benchmark datasets, we applied these techniques specifically to discover compounds for this target protein. This pathway, crucial for metabolizing propionic acid, is essential in pathogenic bacteria for utilizing host-derived lipids and amino acids, making it a promising antimicrobial target. Inefficient removal of propionate can lead to toxic accumulation, threatening microbial survival.In our research, we utilize the latest methods in topological machine learning,multiparameter persistence, to transform the molecular structure of potential compounds into topological vectors for ligand-based drug discovery. By applying our tailored topological model, we prioritized 15 compounds with promising characteristics for inhibiting the active site of methylcitrate dehydratase. Computational molecular docking simulations reveal that these identified compounds interact with key amino acid residues critical to the enzyme’s function. Our findings underscore the power of integrating topology-based modeling with comparative sequencestructure-function analysis and ligand docking. Considering compounds’ geometric fit, energy, and interaction profiles enhances predictions and guides the design of optimized new compounds. This refined approach offers a solid foundation for lead optimization, representing the most promising molecular scaffolds for modification, advancing compound discovery, and providing valuable insights into binding interactions for further experimental validation and potential drug development. Our code is available athttps://github.com/AstritTola/Molecular-Compounds-Targeting
Functional characterization and optimization of protein expression inTreponema denticolashuttle plasmids
Authors: Paula Goetting-Minesky M. , Godovikova Valentina , Saraithong Prakaimuk , Rickard Alexander H. , Crawley Brigette R. , Agolli Sara M. , Fenno J. Christopher 
Published: October 2024

ABSTRACTOral spirochetes are among a small group of keystone pathogens contributing to dysregulation of periodontal tissue homeostasis, leading to breakdown of the tissue and bone supporting the teeth in periodontal disease. Of the greater than sixty oralTreponemaspecies and phylotypes,T. denticolais one of the few that can be grown in culture and the only one in which genetic manipulation has been shown to be practicable.T. denticolais thus a model organism for studying spirochete metabolic processes, interactions with other microbes and host cell and tissue responses relevant to oral diseases as well as venereal and nonvenereal treponematoses. We recently demonstrated enhanced transformation efficiency using a SyngenicDNA-based shuttle plasmid resistant toT. denticolarestriction-modification systems. Here we expand on this work by further characterizing the shuttle plasmid and optimizing expression of cloned genes using several promoter-gene constructs for genetic complementation and exogenous gene expression, including the first inducible system for controlled expression of potentially toxic plasmid-encoded genes inTreponema. Our results highlight the importance of precise pairing of promoters and genes of interest to obtaining biologically optimal protein expression. This work expands the utility of the shuttle plasmid and will facilitate future studies employing shuttle plasmids in analysis ofTreponemaphysiology and behavior.IMPORTANCERigorous genetic analysis in oral spirochetes has been hampered by the limited utility of available versions of theE. coli-T. denticolashuttle plasmid system. We report expanded characterization of the shuttle plasmid, including relative activity of diverse promoters and the first inducible expression system described forT. denticola.We show that careful customization of the shuttle plasmid for specific applications is crucial for obtaining successful results.