bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilirubin-associated single nucleotide polymorphism (SNP) and respiratory health outcomes: a mendelian randomization study
Authors: Baldomero Arianne K. , MacDonald David M. , Kaplan Adam , Lock Eric , Cho Michael H. , Bowler Russell , Gillenwater Lucas , Kunisaki Ken M. , Wendt Chris H. 
Published: July 2023

Abstract
Background
Observational studies have shown an association between higher bilirubin levels and improved respiratory health outcomes. Targeting higher bilirubin levels has been proposed as a novel therapeutic strategy in COPD. However, bilirubin levels are influenced by multiple intrinsic and extrinsic factors, and these observational studies are prone to confounding. Genetic analyses are one approach to overcoming residual confounding in observational studies.

Objectives
To test associations between a genetic determinant of bilirubin levels and respiratory health outcomes.

Methods
COPDGene participants underwent genotyping at the baseline visit. We confirmed established associations between homozygosity for rs6742078 and higher bilirubin, and between higher bilirubin and decreased risk of acute respiratory events within this cohort. For our primary analysis, we used negative binomial regression to test associations between homozygosity for rs6742078 and rate of acute respiratory events.

Results
8,727 participants (n = 6,228 non-Hispanic white and 2,499 African American) were included. Higher bilirubin was associated with decreased rate of acute respiratory events [incidence rate ratio (IRR) 0.85, 95% CI 0.75 to 0.96 per SD increase in bilirubin intensity]. We did not find significant associations between homozygosity for rs6742078 and acute respiratory events (IRR 0.94, 95% CI 0.70 to 1.25 for non-Hispanic white and 1.09, 95% CI 0.91 to 1.31 for African American participants).

Conclusions
A genetic determinant of higher bilirubin levels was not associated with better respiratory health outcomes. These results do not support targeting higher bilirubin levels as a therapeutic strategy in COPD.
Characterizing the urinary proteome of prematurity-associated lung disease in school-aged children
Authors: Course Christopher W , Lewis Philip A , Kotecha Sarah J , Cousins Michael , Hart Kylie , Watkins W John , Heesom Kate J , Kotecha Sailesh 
Published: July 2023

Abstract
Introduction
Although different phenotypes of lung disease after preterm birth have recently been described, the underlying mechanisms associated with each phenotype are poorly understood. We, therefore, compared the urinary proteome for different spirometry phenotypes in preterm-born children with preterm- and term-born controls.

Methods
Preterm and term-born children aged 7–12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection. Urine was analysed by Nano-LC Mass-Spectrometry with Tandem-Mass Tag labelling. The preterm-born children were classified into phenotypes of prematurity-associated preserved ratio impaired spirometry (pPRISm, FEV1 < lower limit of normal (LLN), FEV1/FVC ≥ LLN), prematurity-associated obstructive lung disease (POLD, FEV1 < LLN, FEV1/FVC < LLN) and preterm controls (FEV1 ≥ LLN,). Biological relationships between significantly altered protein abundances were analysed using Ingenuity Pathways Analysis software, and receiver operator characteristic curves were calculated.

Results
Urine was analysed from 160 preterm-born children and 44 term controls. 27 and 21 were classified into the pPRISm and POLD groups, respectively. A total of 785 proteins were detected. Compared to preterm-born controls, sixteen significantly altered proteins in the pPRISm group were linked to six biological processes related to upregulation of inflammation and T-cell biology. In contrast, four significantly altered proteins in the POLD group were linked with neutrophil accumulation. Four proteins (DNASE1, PGLYRP1, B2M, SERPINA3) in combination had an area under the curve of 0.73 for pPRISm and three combined proteins (S100A8, MMP9 and CTSC) had AUC of 0.76 for POLD.

Conclusions
In this exploratory study, we demonstrate differential associations of the urinary proteome with pPRISm and POLD.

Trial registration
EudraCT: 2015-003712-20
A systematic review and meta-analysis on the effect of virtual reality-based rehabilitation for people with Parkinson’s disease
Authors: Kwon Sun-Ho , Park Jae Kyung , Koh Young Ho 
Published: July 2023

Abstract
Background
Virtual reality (VR) is a promising solution for individuals with Parkinson’s disease (PD) who experience symptoms that affect their daily activities and independence. Through VR-based rehabilitation, patients can improve their motor skills in a safe and stress-free environment, making it an attractive alternative to traditional in-person rehabilitation during the COVID-19 pandemic. This study aimed to provide the most recent and convincing evidence on the rehabilitative effects of VR technology compared with conventional treatments.

Methods
Two investigators systematically searched Embase, MEDLINE, CINAHL, PEDro, and the Cochrane Library from their inception until May 31, 2022, to identify randomized controlled trials (RCTs) comparing the effectiveness of VR training with that of conventional treatment for patients with PD. Studies were selected based on the patient, intervention, comparator, and outcome criteria and assessed for the risk of bias using the Cochrane tool. Meta-analysis was conducted by pooling mean differences with 95% confidence intervals.

Results
A total of 14 RCTs, involving 524 participants, were included in the meta-analysis. The results indicated that VR-based rehabilitation significantly improved balance function, as measured using the Berg balance scale (BBS) and activities-specific balance confidence. However, no statistically significant differences in gait ability, activities of daily living, motor function, and quality of life were observed between the experimental and control groups. Subgroup analysis revealed that combination therapy affected heterogeneity in the BBS analysis. Meta-regression analysis demonstrated a significant positive relationship, indicating that more recent studies have shown greater improvements in balance function.

Conclusion
This study’s findings suggest that VR-based rehabilitation is a promising intervention for improving balance function in patients for PD compared with conventional treatment, and recent research supports its efficacy. However, future research should focus on conducting long-term follow-up studies and developing standardized protocols to comprehensively establish this intervention’s potential benefits.
The BinDiscover database: a biology-focused meta-analysis tool for 156,000 GC–TOF MS metabolome samples
Authors: Bremer Parker Ladd , Wohlgemuth Gert , Fiehn Oliver 
Published: July 2023

AbstractMetabolomics by gas chromatography/mass spectrometry (GC/MS) provides a standardized and reliable platform for understanding small molecule biology. Since 2005, the West Coast Metabolomics Center at the University of California at Davis has collated GC/MS metabolomics data from over 156,000 samples and 2000 studies into the standardized BinBase database. We believe that the observations from these samples will provide meaningful insight to biologists and that our data treatment and webtool will provide insight to others who seek to standardize disparate metabolomics studies. We here developed an easy-to-use query interface, BinDiscover, to enable intuitive, rapid hypothesis generation for biologists based on these metabolomic samples. BinDiscover creates observation summaries and graphics across a broad range of species, organs, diseases, and compounds. Throughout the components of BinDiscover, we emphasize the use of ontologies to aggregate large groups of samples based on the proximity of their metadata within these ontologies. This adjacency allows for the simultaneous exploration of entire categories such as “rodents”, “digestive tract”, or “amino acids”. The ontologies are particularly relevant for BinDiscover’s ontologically grouped differential analysis, which, like other components of BinDiscover, creates clear graphs and summary statistics across compounds and biological metadata. We exemplify BinDiscover’s extensive applicability in three showcases across biological domains.
Integrated models of blood protein and metabolite enhance the diagnostic accuracy for Non-Small Cell Lung Cancer
Authors: Xu Runhao , Wang Jiongran , Zhu Qingqing , Zou Chen , Wei Zehao , Wang Hao , Ding Zian , Meng Minjie , Wei Huimin , Xia Shijin , Wei Dongqing , Deng Li , Zhang Shulin 
Published: July 2023

Abstract
Background
For early screening and diagnosis of non-small cell lung cancer (NSCLC), a robust model based on plasma proteomics and metabolomics is required for accurate and accessible non-invasive detection. Here we aim to combine TMT-LC-MS/MS and machine-learning algorithms to establish models with high specificity and sensitivity, and summarize a generalized model building scheme.

Methods
TMT-LC-MS/MS was used to discover the differentially expressed proteins (DEPs) in the plasma of NSCLC patients. Plasma proteomics-guided metabolites were selected for clinical evaluation in 110 NSCLC patients who were going to receive therapies, 108 benign pulmonary diseases (BPD) patients, and 100 healthy controls (HC). The data were randomly split into training set and test set in a ratio of 80:20. Three supervised learning algorithms were applied to the training set for models fitting. The best performance models were evaluated with the test data set.

Results
Differential plasma proteomics and metabolic pathways analyses revealed that the majority of DEPs in NSCLC were enriched in the pathways of complement and coagulation cascades, cholesterol and bile acids metabolism. Moreover, 10 DEPs, 14 amino acids, 15 bile acids, as well as 6 classic tumor biomarkers in blood were quantified using clinically validated assays. Finally, we obtained a high-performance screening model using logistic regression algorithm with AUC of 0.96, sensitivity of 92%, and specificity of 89%, and a diagnostic model with AUC of 0.871, sensitivity of 86%, and specificity of 78%. In the test set, the screening model achieved accuracy of 90%, sensitivity of 91%, and specificity of 90%, and the diagnostic model achieved accuracy of 82%, sensitivity of 77%, and specificity of 86%.

Conclusions
Integrated analysis of DEPs, amino acid, and bile acid features based on plasma proteomics-guided metabolite profiling, together with classical tumor biomarkers, provided a much more accurate detection model for screening and differential diagnosis of NSCLC. In addition, this new mathematical modeling based on plasma proteomics-guided metabolite profiling will be used for evaluation of therapeutic efficacy and long-term recurrence prediction of NSCLC.
The effects of the Posterior X Taping versus augmented feedback on lower‐extremity kinematic and muscle activity pattern during unilateral weight‐bearing activities in men with tibiofemoral varus malalignment
Authors: Hatefi Mohamadreza , Hadadnezhad Malihe , Shojaedin Sadredin , Babakhani Farideh , Tazji Mehdi Khaleghi 
Published: July 2023

AbstractPurposeTibiofemoral Varus Malalignment (TFRV) contributes to overuse injuries by altering lower limb biomechanics. Both Posterior X Taping (PXT) and Real Time Feedback (RTF), have each been recommended for subjects with TFRV as they are thought to enhance control of excessive tibiofemoral rotations. This paper evaluates this claim.MethodsA total of recreational male 24 athletes with TFRV participated in the current study. Kinematic and electromyography variables of lower extremity were synchronously ​recorded on five consecutive repetitions of the single‐legged‐squat (SLS) and forward‐step‐down) FSD) tasks before and after applications of PXT and RTF.ResultsThe subjects at post‐intervention in RTF group exhibited decreased hip adduction during FSD, and decreased hip adduction and internal rotation during eccentric and concentric phases of the SLS; Additionally, we observed increased gluteus medius activity during eccentric phase of the SLS and FSD tasks. In contrast, subjects at the post‐intervention in PXT group exhibited decreased tibiofemoral external rotation and increased ankle external rotation during all the phases of both SLS and FSD tasks.ConclusionThese results suggest that the PXT and RTF interventions are recommended to immediately improve the functional defects of the subjects with TFRV during SLS and FSD tasks.
Effective prevention of post-dural puncture headache with insertion of an intrathecal catheter in parturients: a retrospective study and meta-analysis
Authors: Creazzola F. , Aversano M. , Prencipe F. , Barelli R. , Pasqualetti P. , Simonelli I. , Frigo M. G. 
Published: July 2023

Abstract
Background
Accidental dural puncture is a common complication of labour analgesia. It can trigger post-dural puncture headache, with associated morbidity and increased costs. Intrathecal catheter placement is a prophylactic procedure which can reduce incidence and severity of post-dural puncture headache.

Methods
We conducted a retrospective single-centred study to define incidence and risk factors of accidental dural puncture and post-dural puncture headache in an obstetric population. We also evaluated effectiveness of intrathecal catheter placement compared to epidural catheter replacement in reducing incidence of post-dural puncture headache. We then conducted a systematic review and meta-analysis which included all studies comparing intrathecal catheter placement to epidural catheter replacement in obstetric patients with accidental dural puncture assessing the outcome of reduced incidence of post-dural puncture headache as a dichotomous variable.

Results
Accidental dural puncture had an incidence of 0.25% (60 cases). Of these, 66% developed post-dural puncture headache. A total of 77% (47/60) of patients with accidental dural puncture were treated with an intrathecal catheter placement, while 23% (13/60) had an epidural catheter replacement. Incidence of post-dural puncture headache was lower in the intrathecal catheter group (spinal 26/47, 60.5% epidural 11/13, 84.6%), although not reaching statistical significance (RR 0.71, CI 95%: 0.51–1.00; p = 0.049). The meta-analysis revealed that intrathecal catheter placement significantly reduced incidence of post-dural puncture headache compared to epidural catheter replacement (pooled RR 0.81, 95% CI 0.72–0.91, p < 0.001).

Conclusions
Intrathecal catheter placement is a promising measure to prevent post-dural puncture headache, especially if followed by a pain management protocol and a continuous saline infusion.
AGAP1-associated endolysosomal trafficking abnormalities link gene–environment interactions in neurodevelopmental disorders
Authors: Lewis Sara A. , Bakhtiari Somayeh , Forstrom Jacob , Bayat Allan , Bilan Frédéric , Le Guyader Gwenaël , Alkhunaizi Ebba , Vernon Hilary , Padilla-Lopez Sergio R. , Kruer Michael C. 
Published: July 2023

ABSTRACT
AGAP1 is an Arf1 GTPase-activating protein that regulates endolysosomal trafficking. Damaging variants have been linked to cerebral palsy and autism. We report three new cases in which individuals had microdeletion variants in AGAP1. The affected individuals had intellectual disability (3/3), autism (3/3), dystonia with axial hypotonia (1/3), abnormalities of brain maturation (1/3), growth impairment (2/3) and facial dysmorphism (2/3). We investigated mechanisms potentially underlying AGAP1 variant-mediated neurodevelopmental impairments using the Drosophila ortholog CenG1a. We discovered reduced axon terminal size, increased neuronal endosome abundance and elevated autophagy compared to those in controls. Given potential incomplete penetrance, we assessed gene–environment interactions. We found basal elevation in the phosphorylation of the integrated stress-response protein eIF2α (or eIF2A) and inability to further increase eIF2α phosphorylation with subsequent cytotoxic stressors. CenG1a-mutant flies had increased lethality from exposure to environmental insults. We propose a model wherein disruption of AGAP1 function impairs endolysosomal trafficking, chronically activating the integrated stress response and leaving AGAP1-deficient cells susceptible to a variety of second-hit cytotoxic stressors. This model may have broader applicability beyond AGAP1 in instances where both genetic and environmental insults co-occur in individuals with neurodevelopmental disorders.
Political representation of medical doctors in Switzerland’s executive and legislative branches in 2023
Authors: Smith Alexander , Buadze Anna , Stute Petra , Liebrenz Michael 
Published: July 2023

Background: Healthcare policy is an important societal concern in Switzerland, often dominating the national agenda. In other countries, studies have explored the influence of physicians in public office on healthcare policies, but little is known about the representation of medical doctors in Switzerland's political structures, despite ongoing health-related debates. Methods: In January 2023, we examined the proportion of registered doctors currently serving in Swiss governmental branches: the executive (the Federal Council) and the legislative (the Council of States and the National Council, together the United Federal Assembly). We used publicly available information to demarcate Federal, State, and National Councillors with professional medical backgrounds. We subsequently verified physician registrations using the Federal Office of Public Health’s “Register of Medical Professionals” (MedReg) Results: Six physicians registered in MedReg were identified across the Federal Council and the United Federal Assembly in 2023, equivalent to 2.37% of the total number of Councillors in these chambers. This corresponds to 14.20% of members in the Federal Council (the executive chamber) and 2.03% of members in the United Federal Assembly (the legislative chamber). Conclusions: Rates of physicians sitting in Switzerland’s Federal Council and United Federal Assembly are higher than general population trends for doctors per person. Nonetheless, physicians in Swiss legislative positions are proportionally lower than comparative data from the United States. We highlight how existing professional frameworks may already ensure medical doctors are sufficiently participating in Swiss healthcare debates outside of formal roles. We also suggest that more international evidence is needed to determine the benefits of physicians serving in public office.
The post-award effort of managing and reporting on funded research: a scoping review
Authors: Crane Ksenia , Blatch-Jones Amanda , Fackrell Kathryn 
Published: July 2023

Introduction: Reporting is a mechanism for funding organisations to monitor and manage the progress, outputs, outcomes, and impacts of the research they fund. Inconsistent approaches to reporting and post-award management, and a growing demand for research information, can lead to perception of unnecessary administrative effort that impacts on decision-making and research activity. Identifying this effort, and what stakeholders see as unmet need for improvement, is crucial if funders and Higher Education Institutions (HEIs) are to streamline their practices and provide better support with reporting activities. In this review, we summarise the processes in post-award management, compare current practices, and explore the purpose of collecting information on funded research. We also identify areas where unnecessary effort is perceived and improvement is needed, using previously reported solutions to inform recommendations for funders and HEIs. Methods: We conducted a scoping review of the relevant research and grey literature. Electronic searches of databases, and manual searches of journals and funder websites, resulted in inclusion of 52 records and 11 websites. Information on HEI and funder post-award management processes was extracted, catalogued, and summarised to inform discussion. Results: Post-award management is a complex process that serves many purposes but requires considerable effort, particularly in the set up and reporting of research. Perceptions of unnecessary effort stem from inefficiencies in compliance, data management and reporting approaches, and there is evidence of needed improvement in mechanisms of administrative support, research impact assessment, monitoring, and evaluation. Solutions should focus on integrating digital systems to reduce duplication, streamlining reporting methods, and improving administrative resources in HEIs. Conclusions: Funders and HEIs should work together to support a more efficient post-award management process. The value of research information, and how it is collected and used, can be improved by aligning practices and addressing the specific issues highlighted in this review.
Evaluation of the effect of reduced-dose pneumococcal conjugate vaccine schedules on vaccine serotype carriage in children and their caretakers in a naïve population in Vietnam: Protocol for a cluster randomized non-inferiority trial
Authors: Yoshida Lay-Myint , Flasche Stefan , Mulholland Kim , Nguyen Hien-Anh , Nguyen Cattram , Toizumi Michiko , Dang Duc-Anh 
Published: July 2023

Introduction: The WHO currently recommends giving pneumococcal conjugate vaccines (PCVs) as three doses – either three doses in infancy with Pentavalent vaccine (3p+0), or two doses in infancy followed by a booster around 12 months (2p+1). However, their high price is a barrier to introduction and sustainability in low and middle-income countries. We hypothesize that a schedule with a single priming and a booster dose (1p+1) may maintain similar levels of protection for the community by sustaining herd immunity, once circulation of vaccine types has been controlled. Methods and analysis: We will conduct a cluster randomized trial with four intervention arms (1p+1, 0p+1, 2p+1, 3p+0) and three unvaccinated clusters in the 27 communes of Nha Trang, central Vietnam. A PCV catch-up vaccination campaign to all children under three years of age will be performed at the start of the trial. The primary endpoint is non-inferiority of the1p+1 schedule if compared to the WHO standard 2p+1 and 3p+0 schedules in reducing vaccine serotype carriage prevalence in infants. We will also explore impact of 0p+1 schedule. A baseline and annual pneumococcal carriage surveys of 6480 participants per survey covering infants, toddlers and their mothers will be conducted. Ethics and dissemination: Ethical approvals were obtained from the ethical review committees of Institute of Tropical Medicine, Nagasaki University (151203149-2) and the Ministry of Health, Vietnam (1915/QD-BYT). The results, interpretation and conclusions will be presented at national and international conferences, and published in peer-reviewed open access journals. Trial registration number: NCT02961231
A Rare Case of Visceral Leishmaniasis Diagnosed by Endoscopy in an Anemic Patient With HIV/AIDS
Authors: Dawkins Makeda , Lin Zilan , Cohen Cynthia , Mikkilineni Soumya , Shakil Fouzia , Tewari Virendra 
Published: July 2023

ABSTRACT
Visceral leishmaniasis (VL) is a rare protozoan parasitic disease transmitted by sandfly vectors predominantly found in Asia and Central America. Although far less common than cutaneous leishmaniasis, VL carries a higher mortality burden because of its propensity to cause emaciation and marked anemia through bone marrow infiltration. Treatment is particularly challenging in patients coinfected with HIV before both infections work synergistically to perpetuate immunosuppression, further promoting higher viral loads and disease burden. In comparison with those without HIV, these patients have poorer treatment responses and higher rates of relapse. We describe a case of VL in an anemic patient with HIV/AIDS diagnosed during esophagogastroduodenoscopy. We also present challenges to treatment, adverse drug side effects, and long-term sequelae.