bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of fixed-dose combinations for cardiovascular indications from 2018 to 2023: a nationwide population-based study
Authors: Götzinger Felix , Kieble Marita , Daudí Andrea Espinosa , Kunz Michael , Lauder Lucas , Böhm Michael , Laufs Ulrich , Mahfoud Felix , Schulz Martin 
Published: July 2024

Aims:
Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce.

Methods and results:
Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P = 0.000) but remained negligible.

Conclusion:
Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines.
Head Contact and Suspected Concussion Rates in Youth Basketball: Time to Target Head Contact Penalties for Prevention
Authors: Fehr Christy J. , West Stephen W. , Hagel Brent E. , Goulet Claude , Emery Carolyn A. 
Published: July 2024

Objective:
To compare game events, head contact (HC) rates, and suspected concussion incidence rates (IRs) in boys' and girls' youth basketball.

Design:
Cross-sectional.

Setting:
Canadian club basketball teams (U16-U18).

Participants:
Players from 24 boys' and 24 girls' Canadian club basketball teams during the 2022 season.

Assessment of Risk Factors:
Recorded games were analyzed using Dartfish video analysis software to compare sexes.

Main Outcome Measures:
Poisson regression analyses were used to estimate HCs [direct (HC1) and indirect (HC2)], suspected concussion IRs, and IR ratios (IRRs). Game event, court location, and HC1 fouls were reported.

Results:
Division 1 HC rates did not differ between boys (n = 238; IR = 0.50/10 player-minutes; 95% confidence interval [CI], 0.43-0.56) and girls (n = 220; IR = 0.46/10 player-minutes; 95% CI, 0.40-0.52). Division 2 boys experienced 252 HCs (IR = 0.53/10 player-minutes; 95% CI, 0.46-0.59); girls experienced 192 HCs (IR = 0.40/10 player-minutes; 95% CI, 0.35-0.46). Division 2 boys sustained higher HC1 IRs compared with Division 2 girls (IRR = 1.42; 95% CI, 1.15-1.74). Head contacts, rates did not differ between boys and girls in either Division. Suspected concussion IRs were not significantly different for boys and girls in each Division. Head contacts occurred mostly in the key for boys and girls in each Division. Despite illegality, HC1 penalization ranged from 3.9% to 19.7%. Head contact mechanisms varied across Divisions and sexes.

Conclusions:
Despite current safety measures, both HCs and suspected concussions occur in boys' and girls' basketball. Despite the illegality and potential danger associated with HC, only a small proportion of direct HCs were penalized and therefore targeting greater enforcement of these contacts may be a promising prevention target.
Assessment of the clinical value of five noninvasive predictors of metabolic dysfunction–associated steatotic liver disease in Han Chinese adults
Authors: Ma Xiaopu , Zou Haoxuan , Zhan Junyi , Gao Junzhu , Xie Yan 
Published: July 2024

Background:Fatty Liver Index (FLI), Triglyceride–Glucose Index (TyG), Lipid Accumulation Product (LAP), Zhejiang University Index (ZJU), and Visceral Adiposity Index (VAI) are five classical predictive models for fatty liver disease. Our cross-sectional study aimed to identify the optimal predictors by comparing the predictive value of five models for metabolic dysfunction–associated steatotic liver disease (MASLD) risk.MethodsData on 2687 participants were collected from West China Hospital of Sichuan University. Controlled attenuation parameters assessed by transient elastography were used to effectively diagnose MASLD. Logistic regression analysis was used to estimate the odd ratios and 95% confidence intervals between indices and MASLD risk. Receiver operating characteristic curves were plotted to evaluate the predictive value of indices.ResultsThis study included 1337 normal and 1350 MASLD samples. The average age of MASLD patients is 47 years old, and the prevalence was higher in males (39.3%) than in females (10.9%). Five indices were positively correlated with MASLD risk, with the strongest correlation for TyG. Overall, the area under the curve of the indicators was: ZJU 0.988, FLI 0.987, LAP 0.982, TyG 0.942, and VAI 0.941. In the gender stratification, ZJU (0.989) performed best in males. FLI (0.988) and ZJU (0.987) had similar predictive ability in females. In the age stratification, FLI performed better in predicting the middle-aged group aged 30–40 years (0.991).ConclusionFor Chinese Han adults, ZJU is the best predictive index for initial screening of MASLD. FLI can serve as an alternative tool for ZJU to predict females.
Evaluation of online chat-based artificial intelligence responses about inflammatory bowel disease and diet
Authors: Naqvi Haider A. , Delungahawatta Thilini , Atarere Joseph O. , Bandaru Sumanth Kumar , Barrow Jasmine B. , Mattar Mark C. 
Published: July 2024

Introduction
The USA has the highest age-standardized prevalence of inflammatory bowel disease (IBD). Both genetic and environmental factors have been implicated in IBD flares and multiple strategies are centered around avoiding dietary triggers to maintain remission. Chat-based artificial intelligence (CB-AI) has shown great potential in enhancing patient education in medicine. We evaluate the role of CB-AI in patient education on dietary management of IBD.

Methods
Six questions evaluating important concepts about the dietary management of IBD which then were posed to three CB-AI models – ChatGPT, BingChat, and YouChat three different times. All responses were graded for appropriateness and reliability by two physicians using dietary information from the Crohn’s and Colitis Foundation. The responses were graded as reliably appropriate, reliably inappropriate, and unreliable. The expert assessment of the reviewing physicians was validated by the joint probability of agreement for two raters.

Results
ChatGPT provided reliably appropriate responses to questions on dietary management of IBD more often than BingChat and YouChat. There were two questions that more than one CB-AI provided unreliable responses to. Each CB-AI provided examples within their responses, but the examples were not always appropriate. Whether the response was appropriate or not, CB-AIs mentioned consulting with an expert in the field. The inter-rater reliability was 88.9%.

Discussion
CB-AIs have the potential to improve patient education and outcomes but studies evaluating their appropriateness for various health conditions are sparse. Our study showed that CB-AIs have the ability to provide appropriate answers to most questions regarding the dietary management of IBD.
Real-life experiences of switching from intravenous to subcutaneous vedolizumab maintenance therapy in patients with inflammatory bowel disease
Authors: Kolehmainen Sara , Rautakorpi Jaakko , Löyttyniemi Eliisa , af Björkesten Clas-Göran , Arkkila Perttu , Salminen Kimmo , Sipponen Taina 
Published: July 2024

Background
A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking.

Objective
The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations.

Methods
We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres.

Results
Altogether, 103 patients (26 Crohn’s disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients (P = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml).

Conclusion
Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.
Evidence for low affinity of GABA at the vesicular monoamine transporter VMAT2 – implications for transmitter co-release from dopamine neurons
Authors: Limani Fabian , Srinivasan Sivakumar , Hanzlova Michaela , La Batide-Alanore Ségolène , Klotz Sigrid , Hnaskoxs Thomas S. , Steinkellner Thomas 
Published: July 2024

AbstractBackground and PurposeMidbrain dopamine (DA) neurons comprise a heterogeneous population of cells. For instance, some DA neurons express the vesicular glutamate transporter VGLUT2 allowing these cells to co-release DA and glutamate. Additionally, GABA may be co-released from DA neurons. However, most cells do not express the canonical machinery to synthesize GABA or the vesicular GABA transporter VGAT. Instead, GABA seems to be taken up into DA neurons by a plasmalemmal GABA transporter (GAT1) and stored in synaptic vesicles via the vesicular monoamine transporter VMAT2. Yet, it remains unclear whether GABA indeed interacts with VMAT2, or whether another transmitter could be responsible for the observed inhibitory effects attributed to GABA.Experimental ApproachWe used radiotracer flux measurements in VMAT2 expressing HEK-293 cells and synaptic vesicles from rodents to determine whether GABA qualifies as substrate at VMAT2. mRNAin situhybridization was employed to determine expression of VMAT2 and GAT1 transcripts in DA neurons of mouse and in human midbrains.Key ResultsWe found that GABA reduced uptake of VMAT2 substrates in rodent synaptic vesicle preparations from striatum and cerebellum at millimolar concentrations but had no effect in VMAT2-expressing cells indicating that key components are missing in a non-neuronal system. Roughly 60 % of murine and human DA neurons in the substantia nigra express VMAT2 and GAT1 suggesting that many may be capable of co-releasing DA and GABA.Conclusion and ImplicationOur experiments suggest that GABA is a low-affinity substrate at VMAT2 with potential implications for basal ganglia physiology and disease.Bullet point summaryWhat is already knownSubpopulations of dopamine neurons co-release glutamate and/or GABA.While glutamate is loaded into vesicles by VGLUT2, GABA co-release depends on GAT1 and VMAT2.What this study addsThe relative affinity of GABA at VMAT2 was found to be in the millimolar range.Human midbrain dopamine neurons express GAT1.Clinical significanceGABA co-release from midbrain dopamine neurons may also occur in humans.GABA co-release from dopamine neurons may play a role in neuropsychiatric diseases
A Universal, Single-Component Multilayered Self-Assembling Protein Nanoparticle Vaccine Based on Extracellular Domains of Matrix Protein 2 Against Both Influenza A and B
Authors: Zhang Yi-Nan , Gomes Keegan Braz , Lee Yi-Zong , Ward Garrett , Xie Bomin , Auclair Sarah , He Linling , Zhu Jiang 
Published: July 2024

AbstractThe development of an effective and broadly protective influenza vaccine against circulating and emerging strains remains elusive. In this study, we evaluated single-component self-assembling protein nanoparticles (1c-SApNPs) presenting the conserved matrix protein 2 ectodomain (M2e) from influenza A and B viruses (IAV and IBV, respectively) as a universal influenza vaccine. We previously designed a tandem antigen comprising three IAV M2e domains of human, avian/swine, and human/swine origins (termed M2ex3). The M2ex3-presenting 1c-SApNPs conferred complete protection in mice against sequential lethal challenges with H1N1 and H3N2. To broaden this protection to counter IBVs, we designed a series of antigens incorporating different arrangements of three IAV M2e domains and three copies of IBV M2e. The tandem repeats of IAV and IBV (termed influenza A-B) M2e arrayed on the I3-01v9a 60-mer 1c-SApNP, when formulated with an oil-in-water emulsion adjuvant, generated greater M2e-specifc immunogenicity and protective efficacy than the soluble influenza A-B M2e trimer, as indicated by higher survival rates and lower weight loss post-challenge. Importantly, one of the influenza A-B M2e SApNP constructs elicited 100% protection against a lethal influenza A (H1N1) challenge in mice and 70% protection against a lethal influenza B (Yamagata lineage) challenge, the latter of which has not been reported in the literature to date. Our study thus provides a truly universal single-component M2e-based vaccine candidate against two major types of influenza virus circulating in humans.
In vivo CRISPR base editing for treatment of Huntington’s disease
Authors: Shirguppe Shraddha , Gapinske Michael , Swami Devyani , Gosstola Nicholas , Acharya Pankaj , Miskalis Angelo , Joulani Dana , Szkwarek Maddie G. , Bhattacharjee Abhishek , Elias Gianna , Stilger Michelle , Winter Jackson , Woods Wendy S. , Anand Daphine , Lim Colin K.W. , Gaj Thomas , Perez-Pinera Pablo 
Published: July 2024

ABSTRACTHuntington’s disease (HD) is an inherited and ultimately fatal neurodegenerative disorder caused by an expanded polyglutamine-encoding CAG repeat within exon 1 of the huntingtin (HTT) gene, which produces a mutant protein that destroys striatal and cortical neurons. Importantly, a critical event in the pathogenesis of HD is the proteolytic cleavage of the mutant HTT protein by caspase-6, which generates fragments of the N-terminal domain of the protein that form highly toxic aggregates. Given the role that proteolysis of the mutant HTT protein plays in HD, strategies for preventing this process hold potential for treating the disorder. By screening 141 CRISPR base editor variants targeting splice elements in the HTT gene, we identified platforms capable of producing HTT protein isoforms resistant to caspase-6-mediated proteolysis via editing of the splice acceptor sequence for exon 13. When delivered to the striatum of a rodent HD model, these base editors induced efficient exon skipping and decreased the formation of the N-terminal fragments, which in turn reduced HTT protein aggregation and attenuated striatal and cortical atrophy. Collectively, these results illustrate the potential for CRISPR base editing to decrease the toxicity of the mutant HTT protein for HD.
Single-cell omics for complex microbial communities
Authors: Lan Xihong , Liang Qiaoxing , Wu Jiayi , He Jinhua , Zhang Xiaoying , Li Fei , Zhao Guoping , Guo Ruidong , Jia Huijue 
Published: July 2024

AbstractDespite over a decade of effort, microbial single-cell genomics and transcriptomics remain a challenge, especially for complex communities such as the human microbiome. Here we report a solution based on the Laser-Induced Forward Transfer (LIFT) technology, which circumvent the need for droplet microfluidics and complex barcoding, and allow selective amplification of the genome and the transcriptome of commensal bacteria from complex samples. We capture the diverse oral microbiome, and elucidate the single-cell transcriptome in sporulation. This single-cell method is both scalable and precise, and enables investigation into tissue samples. The approach shows great promise for elucidating the single-cell fate of microbial populations and the native environment of the host-associated microbiome.
Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder
Authors: Mamah Daniel , Patel Aakash , Chen ShingShiun , Wang Yong , Wang Qing 
Published: July 2024

ABSTRACTBackgroundMultiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been fewin vivotools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies.MethodsWe acquired one-hour-long high-directional diffusion MRI data from young control (CON,n=27), schizophrenia (SCZ,n=21), and bipolar disorder (BPD,n=21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants.ResultsIn SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups.ConclusionOur findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.
Identification of the Risk Factors for Complex-Multiple Long-term Conditions (C-MLTC): A Scoping Review
Authors: Heneghan Carl J. , Brassey Jon , Sheppard James P. , Tsiachristas Apostolos , Bhui Kamaldeep , Perera Rafael , Bennett Derrick , Onakpoya Igho J. 
Published: July 2024

ABSTRACTBackgroundComplex multiple long-term conditions (C-MLTC) are commonly defined as the presence of four or more long-term conditions, and their prevalence is projected to increase significantly over the next decade.MethodsWe undertook a scoping review of the literature to identify available evidence on the risk factors for C-MLTC and map out the potential clusters. We focussed on a subset of 18 chronic conditions because they include the most commonly reported and prevalent conditions in the general population. For guidelines we searched NICE Clinical Knowledge Summaries (CKS) and for systematic reviews we searched PubMed, Google Scholar and the TRIP database.ResultsWe found 53 risk factors associated with 18 long-term conditions. Sixteen of these are linked to C-MLTC, with 11 being modifiable. Although we reviewed 51 systematic reviews, inconsistent reporting made it difficult to quantify the risk factors and conditions associated with C-MLTC. Diabetes mellitus was a risk factor for most other conditions (10), followed by coronary heart disease, hypertension, and chronic kidney disease (each associated with 8 long-term conditions). Additionally, depression and anxiety are commonly associated with other long-term conditions, with 19 and 20 conditions, respectively.ConclusionSeveral risks and conditions contribute to the development of multimorbidity. Anxiety and depression are nearly associated with all long-term conditions. Reporting problems within the existing evidence and a lack of clear definitions prevent adequate quantification of the risks related to C-MLTC.
Responsible leadership and workplace safety: do safety culture and safety motivation matter?
Authors: Yeboah Moses Ahomka , Kalvei Mustapha , Ansong Linda Obeng , Ansong Abraham 
Published: July 2024

PurposeWe sought to examine the effect of responsible leadership on employee safety in the workplace both directly and indirectly through mediation effects of safety motivation and safety culture in the oil and gas industry in Ghana.Design/methodology/approachWe employed a quantitative approach (survey) to collect data from 226 pump attendants of the fuel stations in the Accra Metropolis. This study used PLS-SEM to test the research hypotheses in the study.FindingsOur findings show that leaders’ responsible behaviours had a positive and significant impact on both their employees’ wellbeing and safety as well as their motivation to adhere to safety standards and also imbibe a sense of safety culture in the workplace. Furthermore, the inclusion of safety motivation and safety culture as mediating variables reveal that leaders’ ability to achieve a robust workplace safety through responsible leadership was partially contingent on these organisational factors.Practical implicationsWe highlight that leaders should continuously improve their responsible leadership behaviours and also the management of oil and gas companies should encourage managers to focus on day-to-day interactions with employees on safety-related matters (e.g. effectively inspiring and motivating employees to adhere to safety standards and procedures and applying sanctions when necessary).Originality/valueThis study answers the recent calls for a contingency perspective on the relationship between leadership styles and organisational/employee level outcomes by providing empirical support for our conceptual model which identifies safety motivation and safety culture as important organisational factors by which responsible leaders can positively influence workplace safety.