bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of hyperbaric oxygen therapy for diabetes peripheral neuropathy: A systematic review and meta-analysis
Authors: Weng Jiyan , Ren Haiyong , Guo Qiaofeng , Huang Kai , Ding Liqing 
Published: November 2024

Background:
Diabetes peripheral neuropathy (DPN) is mainly treated with diabetes as a whole, and there is no targeted treatment. Some studies have reported that adjuvant hyperbaric oxygen therapy (HBOT) for DPN has achieved a good effect, our study aimed to evaluate the clinical efficacy and safety of HBOT for DPN and provide reference for the clinic by using a systematic review and meta-analysis.

Methods:
A comprehensive search was conducted across several databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet Database, Chinese BioMedical Database, China Scientific Journal Database, and Wanfang Database, for relevant randomized controlled trials published before July 2022. The population, intervention, comparison, outcomes, study design criteria were used to guide the selection of studies. Meta-analysis was performed using RevMan 5.4 and STATA 14.0, with odds ratios and mean differences along with 95% confidence intervals serving as measures of effect size.

Results:
Fourteen randomized controlled trials were included in the final analysis, comprising 675 patients in the HBOT group and 648 in the standard therapy (ST) group. The HBOT group demonstrated a significantly higher effective treatment rate compared to the ST group (P < .001). Additionally, the HBOT group showed significant improvements in motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNVC) across multiple nerves: median nerve (PMNCV < 0.001, PSNCV = 0.001), ulnar nerve (PMNCV = 0.02, PSNCV < 0.001), peroneal nerve (PMNCV < 0.001, PSNCV < 0.001), and tibial nerve (PMNCV = 0.001, PSNCV = 0.008). Six adverse events were reported in the HBOT group, while no adverse events occurred in the ST group, with no significant difference between the 2 groups. Publication bias was identified in some outcome variables through funnel plots, Begger test, and Egger test.

Conclusions:
HBOT significantly enhances treatment efficacy and nerve conduction velocity in patients with DPN, with few adverse events, making it a safe and effective adjunctive therapy for DPN.
Systematic vitamin K antagonist reversal with prothrombin complex concentrate in patients with mild traumatic brain injury: randomized controlled trial
Authors: Douillet Delphine , Tazarourte Karim , Dehours Emilie , Brice Christian , Andrianjafy Hery , Trinh-Duc Albert , Lasocki Sigismond , Labriffe Matthieu , Riou Jérémie , Roy Pierre-Marie 
Published: November 2024

Background and importance
Traumatic brain injury (TBI) in patients on vitamin K antagonists (VKAs) is linked to a high rate of intracranial hemorrhage (ICH). Rapid reversal can reduce ICH progression and mortality, but its effectiveness depends on the time between bleeding onset and coagulation normalization.

Objective
The PREVACT study aimed to assess the efficacy and safety of prompt systematic reversal of anticoagulation in patients presenting to emergency departments (EDs) for recent mild-TBI while receiving a VKA.

Intervention
A randomized, open-label, blinded-endpoint clinical trial was conducted in 21 French EDs. Patients receiving a VKA, having experienced a TBI within the last 6 h, and presenting a Glasgow Coma Score ≥13 were included. Patients were randomized to systematic immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) before any investigation (intervention group) or standard-of-care signifying reversal only if the initial cranial computed tomography (CT) scan indicated ICH (control group). The primary outcome was the rate of ICH detected on a cranial CT scan 24 h post-inclusion.

Results
The study was prematurely stopped for logistic reasons after the randomization of 202 patients (101 and 101 in the intervention and control groups, respectively, mean age 90; 51.8% female). On the 24-h cranial CT scan, 6 of 98 patients (6.1%) in the intervention group manifested ICH vs. 12 of 99 patients (12.1%) in the control group [odds ratio: 0.47 (95% confidence interval: 0.14–1.44); P = 0.215].

Conclusion
In patients with recent mild-TBI receiving a VKA, systematic prompt reversal with 4f-PCC did not statistically significantly reduce ICH rate at 24 h. However, the study was prematurely stopped and does not exclude a clinically relevant benefit of the strategy tested.

Trial registration
Clinicaltrials.gov (NCT01961804).
Epidemiology of Emergency Department Visits for Children With Clinically Significant Cardiovascular Disease
Authors: Abid Zaynah , Neuman Mark I. , Hall Matt , Anderson Brett R. , Dayan Peter S. 
Published: November 2024

Objective
The aim of the study is to determine the epidemiology, cost, and factors associated with hospital admission, deterioration if hospitalized, and mortality for children with a history of clinically significant cardiovascular disease (CVD) presenting to pediatric emergency departments (EDs).

Study Design
Using the Pediatric Health Information System, we performed a retrospective analysis of ED encounters of children ≤17 years old with clinically significant CVD between 2016 and 2021. Patients were included if they had a cardiovascular complex chronic condition, defined by ICD diagnosis, and procedure codes. We assessed the primary diagnosis, admission rate, ICU transfer rate (as a marker of disease progression), mortality, resource utilization, and costs. We conducted multivariable analyses to identify risk factors for admission, ICU transfer, and mortality.

Results
There were 201,551 ED visits (mean 33,592 ± 3354 per year) among 129,938 children with clinically significant CVD. Most ED encounters had a primary diagnosis of a circulatory (21.1%) or respiratory (19.7%) illness. Seventy-six percent of visits had at least one blood test or imaging study conducted. The overall admission rate was 59.7%, with 28.7% admitted to the ICU, and 6.2% transferred to the ICU after the first 24 hours. The median costs for encounters resulting in admission were $13,605 in US 2023 dollars. In multivariable analyses, younger age, a greater number of noncardiac complex chronic conditions, and CVD type were associated with increased odds of admission, ICU transfer after 24 hours, and mortality (all P < 0.05).

Conclusions
ED visits for children with clinically significant CVD lead to substantial resource utilization, including frequent hospitalization, ICU level of care, and costs. This baseline data aids in the development of prospective studies to inform the appropriate ED management for children with clinically significant CVD.
A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Dual COVID-19-Flu Mucosal Vaccines
Authors: Zhu Jingen , Sha Jian , Batra Himanshu , Jain Swati , Wu Xiaorong , Hendrix Emily K. , Kilgore Paul B. , Sun Keer , Plante Kenneth S. , Plante Jessica A. , Walker Jordyn , Tao Pan , Chopra Ashok K. , Rao Venigalla B. 
Published: November 2024

AbstractA multivalent, rapidly deployable, mucosal vaccine platform is desperately needed to prevent the acquisition and transmission of respiratory infections during epidemics and pandemics. We present one such bacteriophage T4-based platform, and design of dual COVID-19-Flu mucosal vaccines by exploiting its unique architecture. These include: T4’s natural affinity for nasal mucosa, flexible engineering to incorporate multiple antigens, and repeat and symmetric epitope presentation for enhanced B cell responses. Hundreds of SARS-CoV-2 spike trimers and nucleocapsid proteins, and influenza hemagglutinin trimers and M2e peptides, were incorporated into a single phage, creating the highest density nanoparticle presentation yet reported. Intranasal administration of adjuvant-free vaccine induced robust mucosal immunity in mice including, neutralizing antibody and secretory IgA, lung-resident CD4+/CD8+T cells, diverse memory B cells, and complete protection against SARS-CoV-2 and influenza challenges. The noninfectious T4 phage offers an extraordinary platform to rapidly design potent mucosal vaccines against emerging bacterial and viral threats.
Improved heritability partitioning and enrichment analyses using summary statistics with graphREML
Authors: Li Hui , Kamath Tushar , Mazumder Rahul , Lin Xihong , O’Connor Luke 
Published: November 2024

ABSTRACTHeritability enrichment analysis using data from Genome-Wide Association Studies (GWAS) is often used to understand the functional basis of genetic architecture. Stratified LD score regression (S-LDSC) is a widely used method-of-moments estimator for heritability enrichment, but S-LDSC has low statistical power compared with likelihood-based approaches. We introduce graphREML, a precise and powerful likelihood-based heritability partition and enrichment analysis method. graphREML operates on GWAS summary statistics and linkage disequilibrium graphical models (LDGMs), whose sparsity makes likelihood calculations tractable. We validate our method using extensive simulations and in analyses of a wide range of real traits. On average across traits, graphREML produces enrichment estimates that are concordant with S-LDSC, indicating that both methods are unbiased; however, graphREML identifies 2.5 times more significant trait-annotation enrichments, demonstrating greater power compared to the moment-based S-LDSC approach. graphREML can also more flexibly model the relationship between the annotations of a SNP and its heritability, producing well-calibrated estimates of per-SNP heritability.
Polymicrobial interactions betweenStaphylococcus aureusandPseudomonas aeruginosapromote biofilm formation and persistence in chronic wound infections
Authors: Keim Klara , Bhattacharya Mohini , Crosby Heidi A. , Jenul Christian , Mills Krista , Schurr Michael , Horswill Alexander 
Published: November 2024

AbstractChronic, non-healing wounds are a leading cause of prolonged patient morbidity and mortality due to biofilm-associated, polymicrobial infections.Staphylococcus aureusandPseudomonas aeruginosaare the most frequently co-isolated pathogens from chronic wound infections. Competitive interactions between these pathogens contribute to enhanced virulence, persistence, and antimicrobial tolerance.P. aeruginosautilizes the extracellular proteases LasB, LasA, and AprA to degradeS. aureussurface structures, disrupt cellular physiology, and induce cell lysis, gaining a competitive advantage during co-infection.S. aureusevadesP. aeruginosaby employing aggregation mechanisms to form biofilms. The cell wall protein SasG is implicated inS. aureusbiofilm formation by facilitating intercellular aggregation upon cleavage by an extracellular protease. We have previously shown that proteolysis by a host protease can induce aggregation. In this study, we report thatP. aeruginosaproteases LasA, LasB, and AprA cleave SasG to induceS. aureusaggregation. We demonstrate that SasG contributes toS. aureusbiofilm formation in response to interactions withP. aeruginosaproteases by quantifying aggregation, SasG degradation, and proteolytic kinetics. Additionally, we assess the role of SasG in influencingS. aureusbiofilm architecture during co-infectionin vivo,chronic wound co-infections. This work provides further knowledge of some of the principal interactions that contribute toS. aureuspersistence within chronic wounds co-infected withP. aeruginosa,and their impact on healing and infection outcomes.
Vigorous exercise associates with the abundance of gut bacterial species reflecting energy pathways: an epidemiological cross-sectional analysis within the Lifelines Dutch Microbiome Project
Authors: Morwani-Mangnani Jordi , Ducarmon Quinten R. , Zeller Georg , Deelen Joris , Beekman Marian , Slagboom P. Eline 
Published: November 2024

ABSTRACTBackgroundRegular physical activity (PA) is vital for proper organ functions including the gut. Despite existing research, it remains unclear how the gut microbiome is affected by different intensities of PA, and how other lifestyle factors influence this relationship. Here we study the relation between PA intensity and gut microbiome composition and function in a large Lifelines Dutch Microbiome Project dataset.MethodsA cross-sectional design was performed on 5409 adults aged 40 to 60 from the community-based Lifelines Dutch Microbiome Project and from all these participants metagenomic shotgun data was available. Participants were categorized into sedentary (N=2501), moderate (N=1915), and vigorous (N=993) PA groups, based on self-reported activity levels. We investigated association between PA intensity and microbial diversity, bacterial species, and metabolic pathways by multiple regression models sequentially adjusted for the covariates age/sex, BMI, stool consistency and diet quality/alcohol intake.ResultsVigorous PA, but not moderate PA, was significantly associated with higher gut microbiome alpha diversity (i.e., species richness, Shannon diversity, and Simpson diversity) as compared to sedentary PA. Compared to the sedentary group, the vigorous PA group showed a lower abundance of the bacterial speciesLawsonibacter asaccharolyticus(β = −0.003, p = 0.042), even after extensive covariate adjustments and correction for multiple testing. Other species were initially also significantly associated with vigorous PA, but they disappeared after adjusting for covariates resulting in a loss of significance. Pathway analysis showed significant enrichment of two distinct metabolic pathways related to cellular energy recycling (Pyruvate fermentation to acetate and lactate II,β = 8.11×10−05, p = 0.035) and purine metabolism (Purine ribonucleosides degradation, β = 3.36×10−04, p = 0.039) in participants engaging in vigorous PA as compared to sedentary PA.ConclusionsVigorous PA is associated with higher gut microbiome diversity and with specific alterations of microbial composition. The lower abundance ofLawsonibacter asaccharolyticuswithin the vigorous PA group may be linked to increased gut permeability. The identified enrichment of microbial fermentation and purine metabolism in vigorous PA hints at a potential role of PA in affecting gut microbiome functionality and host health. The results of our modeling strategy highlight the importance of adjusting for dietary covariates to understand how PA may impact the gut microbiome independently from other influences.
Do viral-associated pathways underlie the immune activation during the acute phase of severe major depression?
Authors: Maes Michael , Zhang Yingqian , Plaimas Kitiporn , Suratanee Apichat , Li Jing , Almulla Abbas F. 
Published: November 2024

AbstractBackgroundMajor depressive disorder (MDD) and its most severe phenotype, major dysmood disorder (MDMD), are distinguished by the activation of the immune-inflammatory response system, T cell activation, and a relative T regulatory cell suppression. Nevertheless, these immune data were not used to characterize the features of the immune protein-protein interaction (PPI) network of MDMD.ObjectivesTo identify the network’s nodes and bottlenecks as well as the biological processes that are overrepresented in the PPI network, we conducted PPI network, annotation, and enrichment analyses.ResultsThe PPI network analysis has identified the following backbone genes: tumor necrosis factor-α (TNF), interleukin (IL)6, CXCL12, CXCL10, CCL5, cluster of differentiation (CD)4, CD8A, human leukocyte antigen (HLA)-DR, and FOXP3. A “cellular and defense response”, an “immune response system response”, and “a viral process that involves viral protein interaction with cytokines and cytokine receptors” were all highly associated with the network. The chemokine network and TNF and nuclear factor-κB (NFKB) pathways are additional biological pathways that are enriched in the PPI network. Molecular complex detection extracted one component from the data, including viral protein interaction with cytokine and cytokine receptors and “regulated by RELA” (an NFKB subunit).ConclusionsViral processes may underlie the activation of T cells and the cytokine and chemokine networks that are associated with MDMD. Future research on the pathogenesis of MDMD and MDD should examine whether and which viral infections are associated with the onset of these conditions, or whether viral reactivation is associated with the recurrence of illness.
Determinants of antenatal care service utilization among adolescent mothers of (10-19) years of age at Kanyama level one hospital in Lusaka district
Authors: Saka Kenny , Hazemba Alice Ngoma , Bwembya Phoebe 
Published: November 2024

AbstractIntroductionThe provision of adequate antenatal care services is crucial for promoting maternal and child health. Therefore, it is necessary to understand the factors influencing the use of these services, especially among special groups such as adolescents. Adolescents, defined as individuals between the ages of 10 and 19 years, face specific challenges and vulnerabilities during pregnancy and childbirth. Hence, it is vital to develop targeted interventions to improve their reproductive health outcomes. This study analyzed the factors associated with antenatal care utilization among adolescent mothers in Zambia.MethodologyThe study used a cross sectional study design. Data was collected using a structured questionnaire from adolescents who were 8 months pregnant or more and adolescents who were already mothers at Kanyama level one hospital in Lusaka. Descriptive statistics of individual characteristics were developed to describe the data. Associations between ANC utilization and independent variables was tested using the Chi-Square test and multivariate logistic regression.ResultsThe proportion of antenatal care utilization in this study was 39.37%. At multivariate analysis, factors that were significantly associated with antenatal care utilization were past pregnant experience (OR = 0.35; 95% CI: 0.14 to 0.85) and partners education (OR = 1.38; 95% CI: 1.02 to 1.87). However, Partner education did not have a statistical significance between levels of education and ANC utilization. This could have been due to a small sample size. Other studies however, reviewed a significant statistical relationship between levels of education and adolescent ANC utilization.ConclusionThe findings underscore a low proportion of antenatal care utilization among adolescent mothers. Particularly low proportion of ANC utilization was found in adolescents mothers who had never experienced pregnancy in the past.
Intraflagellar transport protein IFT172 contains a C-terminal ubiquitin-binding U-box-like domain involved in ciliary signaling
Authors: Zacharia Nevin K. , Kuhns Stefanie , Boegholm Niels , Christensen Anni , Wang Jiaolong , Petriman Narcis A. , Lorentzen Anna , Fialova Jindriska L. , Menguy Lucie , Saunier Sophie , Christensen Soren T. , Andersen Jens S. , Bhogaraju Sagar , Lorentzen Esben 
Published: November 2024

AbstractIntraflagellar transport (IFT) is a fundamental process driving ciliogenesis in most eukaryotic organisms. IFT172, the largest protein of the IFT complex, plays a crucial role in cilium formation and is associated with several disease variants causing ciliopathies. While IFT172 is tethered to the IFT-B complex via its N-terminal domains, the function of its C-terminal domains has remained elusive. Here, we reveal that the C-terminal part of IFT172 interacts with IFT-A complex subunits, providing a molecular basis for the role of IFT172 in bridging IFT-A and IFT-B complexes. We determine the crystal structure of the C-terminal part of IFT172, uncovering a conserved U-box-like domain often found in E3 ubiquitin ligases. This domain exhibits ubiquitin-binding properties and auto-ubiquitination activity. The IFT172 auto-ubiquitination activity is reduced in the C1727R patient ciliopathy variant. We use CRISPR-engineered RPE-1 cells to demonstrate that the U-box-like domain is essential for IFT172 protein stability and proper cilium formation. Notably, RPE-1 cells with heterozygous deletion of the U-box domain show altered TGFB signaling responses, particularly in SMAD2 phosphorylation levels and AKT activation. Our findings suggest a novel dual role for IFT172 in both structural support within IFT trains and regulation of ciliary ubiquitination and signaling pathways, providing new insights into the molecular mechanisms underlying IFT172-related ciliopathies.
Advancing Plant Metabolic Research By Using Large Language Models To Expand Databases And Extract Labelled Data
Authors: Knapp Rachel , Johnson Braidon , Busta Lucas 
Published: November 2024

AbstractPremise: Recently, plant science has seen transformative advances in scalable data collection for sequence and chemical data. These large datasets, combined with machine learning, revealed that conducting plant metabolic research on large scales yields remarkable insights. A key next step in increasing scale has been revealed with the advent of accessible large language models, which, even in their early stages, can distill structured data from literature. This brings us closer to creating specialized databases that consolidate virtually all published knowledge on a topic. Methods: Here, we first test different prompt engineering technique / language model combinations in the identification of validated enzyme-product pairs. Next, we evaluate automated prompt engineering and retrieval augmented generation applied to identifying compound-species associations. Finally, we build and determine the accuracy of a multimodal language model-based pipeline that transcribes images of tables into machine-readable formats. Results: When tuned for each specific task, these methods perform with high accuracies (80-90 percent for enzyme-product pair identification and table image transcription), or with modest accuracies (50 percent) but lower false-negative rates than previous methods (down to 40 percent from 55 percent) for compound-species pair identification. Discussion: We enumerate several suggestions for working with language models as researchers, among which is the importance of the user’s domain-specific expertise and knowledge.Significance StatementScientific databases have played a major role in advancing metabolic research. However, even today’s advanced databases are incomplete and/or are not built to best suit certain research tasks. Here, we explored and evaluated the use of large language models and various prompt engineering techniques to expand and subset existing databases in task-specific ways. Our results illustrate the potential for high-accuracy additions and restructurings of existing databases using language models, assuming the specific methods by which the models are used are tuned and validated for the specific task. These findings are important because they outline a method by which we could greatly expand existing databases and rapidly tailor them to specific research efforts, leading to greater research productivity and effective utilization of past research findings.All authors collected data, analyzed data, prepared the manuscript, and approved its final version. The authors declare that they have no competing interests.