bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss-of-function variants in
JPH1
cause congenital myopathy with prominent facial and ocular involvement
Authors: Johari Mridul , Topf Ana , Folland Chiara , Duff Jennifer , Dofash Lein , Marti Pilar , Robertson Thomas , Vilchez Juan , Cairns Anita , Harris Elizabeth , Marini-Bettolo Chiara , Hundallah Khalid , Alhashem Amal M , Al-Owain Mohammed , Maroofian Reza , Ravenscroft Gianina , Straub Volker 
Published: August 2024

Background

Weakness of facial, ocular and axial muscles is a common clinical presentation in congenital myopathies caused by pathogenic variants in genes encoding triad proteins. Abnormalities in triad structure and function resulting in disturbed excitation-contraction coupling and Ca
2+
homeostasis can contribute to disease pathology.

Methods
We analysed exome and genome sequencing data from four unrelated individuals with congenital myopathy characterised by facial, ocular and bulbar involvement. We collected deep phenotypic data from the affected individuals. We analysed the RNA-sequencing (RNA-seq) data of F3-II.1 and performed gene expression outlier analysis in 129 samples.

Results
The four probands had a remarkably similar clinical presentation with prominent facial, ocular and bulbar features. Disease onset was in the neonatal period with hypotonia, poor feeding, cleft palate and talipes. Muscle weakness was generalised but prominent in the lower limbs with facial weakness also present. All patients had myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability. Muscle biopsy on light microscopy showed type 1 myofiber predominance and ultrastructural analysis revealed slightly reduced triads, and structurally abnormal sarcoplasmic reticulum.

DNA sequencing identified four unique homozygous loss-of-function variants in
JPH1
, encoding junctophilin-1 in the four families; one stop-gain (c.354C>A;p.Tyr118*) and three frameshift (c.373delG;p.Asp125Thrfs*30, c.1738delC;p.Leu580Trpfs*16 and c.1510delG;p. Glu504Serfs*3) variants. Muscle RNA-seq showed strong downregulation of
JPH1
in the F3 proband.

Conclusions

Junctophilin-1 is critical for the formation of skeletal muscle triad junctions by connecting the sarcoplasmic reticulum and T-tubules. Our findings suggest that loss of
JPH1
results in a congenital myopathy with prominent facial, bulbar and ocular involvement.
Anxiety and its relationship to demographic and personality traits data among special operations divers: a cross-sectional study
Authors: Zhao Houyu , Wen Y , Liang K , Huang J , Fang Y 
Published: August 2024

IntroductionSpecial operation diving is becoming increasingly prevalent but has received less attention. The anxiety profile in special operation divers and its influencing factors remain unclear, posing great challenges to medical and psychological security of this unique population. The current study aimed to investigate the anxiety profile and to analyse the correlations between anxiety with demographic and personality traits data among special operation divers.MethodsFrom July to October 2023, 650 special operation divers participated this analytical cross-sectional study. The Spielberg’s State-Trait Anxiety Inventory and the Neuroticism Extraversion Openness Five-Factor Inventory were used to evaluate anxiety and personality traits of special operation divers.Results27.2% and 30.3% special operation divers showed high scores on state anxiety and trait anxiety, respectively. Special operation divers who are 30 years or older and who have dived for 15 years or more are prone to higher level of trait anxiety and state anxiety (all p<0.001). Neuroticism showed a significantly positive correlation with both trait anxiety (r=0.675, p<0.001) and state anxiety (r=0.674, p<0.001). Extraversion, openness, agreeableness and conscientiousness are all negatively correlated with both trait anxiety and state anxiety (r=−0.670 to −0.400, all p<0.001). Additionally, significant differences in neuroticism, extraversion, openness, agreeableness and conscientiousness were observed between the high anxiety group and the low anxiety group (all p<0.001).ConclusionThe prevalence of trait anxiety and state anxiety are both relatively high among special operation divers. Individuals with older age and longer diving years are more prone to be anxious. Higher neuroticism, lower extraversion, lower openness, lower agreeableness and lower conscientiousness may be predictors of higher trait anxiety and higher state anxiety.
Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease
Authors: Felten Renaud , Foray Anne-Perrine , Schneider Pascal , Marquet Cindy , Pecquet Coralie , Monneaux Fanny , Dumortier Hélène , Sibilia Jean , Valette Fabrice , Chatenoud Lucienne , Gottenberg Jacques-Eric 
Published: August 2024

IntroductionThe therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren’s disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD.Material and methodsFemale NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis.ResultsBAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3+regulatory and CD3+CD4−CD8−double negative T-cell numbers in SGs.ConclusionA monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.
Doxycycline post-exposure prophylaxis among men who have sex with men and transgender women in Belgium: awareness, use and antimicrobial resistance concerns in a cross-sectional online survey
Authors: Vanbaelen Thibaut , Rotsaert Anke , De Baetselier Irith , Platteau Tom , Hensen Bernadette , Reyniers Thijs , Kenyon Chris 
Published: August 2024

ObjectivesWe aimed to assess the awareness, willingness to use and use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR).MethodsCross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organisations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ2or Fisher’s exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR.Results875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32–48), 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the previous 6 months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with reporting ≥1 sexually transmitted infection (STI) in the previous 12 months, engagement in chemsex, HIV status and pre-exposure prophylaxis use, and education level.About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use decreased to 60% and concerns of side effects/AMR increased to around 70%.ConclusionsApproximately 1 in 10 MSM in Belgium reported using doxyPEP. A recent history of STIs and STI risk factors were positively associated with doxyPEP use. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.
Validation of the Chicken Femur as a Model for the Human Metacarpal: An In-Vitro Analysis
Authors: LOBO Abhirup , ACKLAND David , ROBINSON Dale , THAM Stephen K. Y. 
Published: August 2024

Background: The aim of this study was to evaluate the chicken femur as a laboratory model for the human metacarpal by comparing the bone microarchitecture and mechanical properties of chicken femurs to human cadaveric metacarpals. Methods: Sixteen fresh chicken femora and 20 fresh frozen cadaveric human metacarpals were imaged using a micro computed tomography scanner. The bones were then mechanically tested using four-point-bending and torsional testing. Results: There were no significant differences in macroscopic features between chicken femora and human metacarpals, including overall length, external radius, internal radius, cortical width and cross-sectional area of the diaphyseal cortex (p > 0.05). There were no significant differences in the trabecular number and spacing in the distal metaphysis of both groups (p > 0.05). The diaphysis and proximal metaphysis did not share any microarchitectural similarities. Four-point bending tests resulted in significantly higher yield forces, ultimate force, failure points and stiffness in human metacarpals (p < 0.05). Torsion tests resulted in significant higher ultimate torque and torsional rigidity in human metacarpals (p < 0.05). Conclusions: The chicken femur has structural and biomechanical differences to the fresh frozen human metacarpal despite the similarity in their macroscopic features.
Comparative Study of Trapeziectomy with Weilby Suspensionplasty versus Implant Arthroplasty for Thumb Carpometacarpal Joint Arthritis in an Asian Population
Authors: TAN Tuan Hao , KANG Hui Ying Gavrielle 
Published: August 2024

Background: This retrospective study compares the outcomes of trapeziectomy and Weilby suspensionplasty procedure versus implant arthroplasty using the TOUCH® prosthesis for basilar thumb arthritis in an Asian population. Methods: A total of 15 consecutive thumbs in 13 patients were included in this study. Six patients (2 male, 4 female, mean age of 62 years old) underwent trapeziectomy and Weilby suspensionplasty procedure. Seven patients (4 male, 3 female, mean age 63 years old) underwent implant CMCJ arthroplasty using the TOUCH® prosthesis. Data collected include demographics, severity of arthritis on plain radiographs of the thumb basilar joint, length of follow-up, pre- and postoperative pain levels, Kapandji thumb opposition score, grip and pinch strength and the time taken to return to work. Results: Patients in the trapeziectomy and Weilby suspensionplasty group had a mean follow-up of 4.5 months, while those in the TOUCH® implant arthroplasty group had a mean follow-up of 14 months. TOUCH® implant arthroplasty patients showed significantly higher grip strengths at 3 months post-surgery and a shorter return to work. There were no differences in pinch strength at 3 months, pinch or grip strength at 6 months or pain scores. Complications included prolonged scar hypersensitivity in two patients who underwent the Weilby suspensionplasty and a dislocated TOUCH® implant cup in one patient. Conclusions: Our study suggests that in the short term, CMCJ implant arthroplasty with the TOUCH® prosthesis produces results comparable to trapeziectomy and Weilby suspensionplasty. Level of Evidence: Level III (Therapeutic)
The Impact of Fetal Growth Restriction on Prenatal 2D Ultrasound and Doppler Study of the Fetal Adrenal Gland
Authors: Pattamathamakul Suphawan , Duangkum Chatuporn , Chaiyarach Sukanya , Kongwattanakul Kiattisak , Saksiriwuttho Piyamas , Komwilaisak Ratana , Chantanavilai Sathida , Pongsamakthai Manasicha , Sirikarn Prapassara 
Published: August 2024

Background: Uteroplacental insufficiency in fetuses with growth restriction (FGR) leads to chronic hypoxia and stress, predominantly affecting the adrenal glands. However, the mechanisms of impact remain unclear.Objectives: This study is aimed at comparing the Doppler indices of the adrenal artery and the adrenal gland sizes between FGR and those with normal growth.Materials and Methods: A multicenter, cross‐sectional study was conducted from February to December 2023. We compared 34 FGR to 34 with normal growth in terms of inferior adrenal artery (IAA) Doppler indices and adrenal gland volumes.Results: The IAA peak systolic velocity (PSV) in the FGR group was 14.9 ± 2.9 cm/s compared to 13.5 ± 2.0 cm/s in the normal group, with a mean difference of 1.4 cm/s (95% confidence interval [CI]: 0.27–2.65; p value = 0.017). There were no significant differences between groups in terms of IAA pulsatility index (PI), resistance index (RI), or systolic/diastolic (S/D), with p values of 0.438, 0.441, and 0.658, respectively. The volumes of the corrected whole adrenal gland and the corrected neocortex were significantly larger in the FGR group, with p values of 0.031 and 0.020, respectively.Conclusion: Both increased IAA PSV and enlarged volumes of the corrected whole adrenal gland and neocortex were found in fetuses with FGR, suggesting significant adrenal gland adaptation in response to chronic intrauterine stress.
Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Authors: Drabison Thomas , Boeckman Mike , Yang Yan , Huang Kevin M. , de Bruijn Peter , Nepal Mahesh R. , Silvaroli Josie A. , Chowdhury Anika T. , Eisenmann Eric D. , Cheng Xiaolin , Pabla Navjotsingh , Mathijssen Ron H.J. , Baker Sharyn D. , Hu Shuiying , Sparreboom Alex , Talebi Zahra 
Published: August 2024

Abstract

Although the primary elimination pathway for most tyrosine kinase inhibitors (TKI) involves CYP3A4-mediated metabolism, the mechanism by which these agents are brought into hepatocytes remains unclear. In this study, we optimized and validated a competitive counterflow (CCF) assay to examine TKIs as substrates of the hepatic uptake transporter OATP1B1. The CCF method was based on the stimulated efflux of radiolabeled estradiol-17β-glucuronide under steady-state conditions in HEK293 cells engineered to overexpress OATP1B1. Of the 62 approved TKIs examined, 13 agents were identified as putative substrates of OATP1B1, and pazopanib was selected as a representative hit for further validation studies. The transport of pazopanib by OATP1B1 was confirmed by decreased activity of its target VEGFR2 in OATP1B1-overexpressing cells, but not cells lacking OATP1B1, consistent with molecular docking analyses indicating an overlapping binding orientation on OATP1B1 with the known substrate estrone-3-sulfate. In addition, the liver-to-plasma ratio of pazopanib in vivo was decreased in mice with a deficiency of the orthologous transporters, and this was accompanied by diminished pazopanib-induced hepatotoxicity, as determined by changes in the levels of liver transaminases. Our study supports the utility of CCF assays to assess substrate affinity for OATP1B1 within a large set of agents in the class of TKIs and sheds light on the mechanism by which these agents are taken up into hepatocytes in advance of metabolism.

Significance:
Despite the established exposure–pharmacodynamic relationships for many TKIs, the mechanisms underlying the agents’ unpredictable pharmacokinetic profiles remain poorly understood. We report here that the disposition of many TKIs depends on hepatic transport by OATP1B1, a process that has toxicologic ramifications for agents that are associated with hepatotoxicity.
Prognostic Significance of Hemodynamics in Patients With Transposition of the Great Arteries and Systemic Right Ventricle
Authors: Aldweib Nael , Deghani Payam , Broberg Craig S. , van Dissel Alexandra , Altibi Ahmad , Wong Joshua , Baker David , Gindi Salil , Khairy Paul , Opotowsky Alexander R. , Shah Sangeeta , Magalski Anthony , Cramer Jonathan , Kauling Robert M. , Dellborg Mikael , Krieger Eric V. , Yeung Elizabeth , Roos-Hesselink Jolien , Aboulhosn Jamil , Nicolarsen Jeremy , Masha Luke , Gallego Pastora , Celermajer David S. , Kay Joseph , Vonder Muhll Isabelle , Jameson Susan M. , O’Donnell Clare , Fusco Flavia , John Anitha S. , Macon Conrad , Antonova Petra , Cotts Timothy , Sarubbi Berardo , Rodriguez Fred , DeZorzi Christopher , Jayadeva Pavithra S. , Kuo Marissa , Kutty Shelby , Gupta Tripti , Burchill Luke J. , Rodriguez Monserrate Carla P. , Lubert Adam M. , Grewal Jasmine , Pylypchuk Stephen , Belkin Mark N. , Wilson William M. 
Published: August 2024

BACKGROUND:
Patients with transposition of the great arteries (TGA) and systemic right ventricle often confront significant adverse cardiac events. The prognostic significance of invasive hemodynamic parameters in this context remains uncertain. Our hypothesis is that the aortic pulsatility index and hemodynamic profiling utilizing invasive measures provide prognostic insights for patients with TGA and a systemic right ventricle.

METHODS:

This retrospective multicenter cohort study encompasses adults with TGA and a systemic right ventricle who underwent cardiac catheterization. Data collection, spanning from 1994 to 2020, encompasses clinical and hemodynamic parameters, including measured and calculated values such as pulmonary capillary wedge pressure, aortic pulsatility index, and cardiac index. Pulmonary capillary wedge pressure and cardiac index values were used to establish 4 distinct hemodynamic profiles. A pulmonary capillary wedge pressure of ≥15 mm Hg indicated congestion, termed wet, while a cardiac index <2.2 L/min per m
2
signified inadequate perfusion, labeled cold. The primary outcome comprised a composite of all-cause death, heart transplantation, or the requirement for mechanical circulatory support.

RESULTS:

Of 1721 patients with TGA, 242 individuals with available invasive hemodynamic data were included. The median follow-up duration after cardiac catheterization was 11.4 (interquartile range, 7.5–15.9) years, with a mean age of 38.5±10.8 years at the time of cardiac catheterization. Among hemodynamic parameters, an aortic pulsatility index <1.5 emerged as a robust predictor of the primary outcome, with adjusted hazard ratios of 5.90 (95% CI, 3.01–11.62;
P
<0.001). Among the identified 4 hemodynamic profiles, the cold/wet profile was associated with the highest risk for the primary outcome, with an adjusted hazard ratio of 3.83 (95% CI, 1.63–9.02;
P
<0.001).

CONCLUSIONS:
A low aortic pulsatility index (<1.5) and the cold/wet hemodynamic profile are linked with an elevated risk of adverse long-term cardiac outcomes in patients with TGA and systemic right ventricle.
Comparative Cardiovascular Effectiveness of Empagliflozin Versus Dapagliflozin in Adults With Treated Type 2 Diabetes: A Target Trial Emulation
Authors: Bonnesen Kasper , Heide-Jørgensen Uffe , Christensen Diana H. , Lash Timothy L. , Hennessy Sean , Matthews Anthony , Pedersen Lars , Thomsen Reimar W. , Schmidt Morten 
Published: August 2024

BACKGROUND:
Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown.

METHODS:
This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event). Participants were followed until an outcome, emigration, or death occurred; 6 years after initiation; or December 31, 2021, whichever occurred first. Logistic regression was used to compute inverse probability of treatment and censoring weights, controlling for 57 potential confounders. In intention-to-treat analyses, 6-year adjusted risks, risk differences, and risk ratios, considering noncardiovascular death competing events, were estimated. Analyses were stratified by coexisting atherosclerotic cardiovascular disease and HF. A per-protocol design was performed as a secondary analysis.

RESULTS:
There were 36 670 eligible empagliflozin and 20 606 eligible dapagliflozin initiators. In the intention-to-treat analysis, the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% [95% CI, −0.9% to 1.0%]; risk ratio, 1.00 [95% CI, 0.91 to 1.11]). The findings were consistent in people with atherosclerotic cardiovascular disease (risk difference, −2.3% [95% CI, −8.2% to 3.5%]; risk ratio, 0.92 [95% CI, 0.74 to 1.14]) and without atherosclerotic cardiovascular disease (risk difference, 0.3% [95% CI, −0.6% to 1.2%]; risk ratio, 1.04 [95% CI, 0.93 to 1.16]) and in people with HF (risk difference, 1.1% [95% CI, −6.5% to 8.6%]; risk ratio, 1.04 [95% CI, 0.79 to 1.37]) and without HF (risk difference, −0.1% [95% CI, −1.0% to 0.8%]; risk ratio, 0.99 [95% CI, 0.90 to 1.09]). The 6-year risks of major adverse cardiovascular event were also not different in the per-protocol analysis (9.1% versus 8.8%; risk difference, 0.2% [95% CI, −2.1% to 2.5%]; risk ratio, 1.03 [95% CI, 0.80 to 1.32]).

CONCLUSIONS:
Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes with or without coexisting atherosclerotic cardiovascular disease or HF.
Sex Disparities in the Management of Acute Coronary Syndromes: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program
Authors: Sola Michael , Mesenbring Elise , Glorioso Thomas J. , Gualano Sarah , Atkinson Tamara , Duvernoy Claire S. , Waldo Stephen W. 
Published: August 2024

Background
Previous work has demonstrated disparities in the management of cardiovascular disease among men and women. We sought to evaluate these disparities and their associations with clinical outcomes among patients admitted with acute coronary syndromes to the Veterans Affairs Healthcare System.

Methods and Results
We identified all patients that were discharged with acute coronary syndromes within the Veterans Affairs Healthcare System from October 1, 2015 to September 30, 2022. Medical and procedural management of patients was subsequently assessed, stratified by sex. In doing so, we identified 76 454 unique admissions (2327 women, 3.04%), which after propensity matching created an analytic cohort composed of 6765 men (74.5%) and 2295 women (25.3%). Women admitted with acute coronary syndromes were younger with fewer cardiovascular comorbidities and a lower prevalence of preexisting prescriptions for cardiovascular medications. Women also had less coronary anatomic complexity compared with men (5 versus 8, standardized mean difference [SMD]=0.40), as calculated by the Veterans Affairs SYNTAX score. After discharge, women were significantly less likely to receive cardiology follow‐up at 30 days (hazard ratio [HR], 0.858 [95% CI, 0.794–0.928]) or 1 year (HR, 0.891 [95% CI, 0.842–0.943]), or receive prescriptions for guideline‐indicated cardiovascular medications. Despite this, 1‐year mortality rates were lower for women compared with men (HR, 0.841 [95% CI, 0.747–0.948]).

Conclusions
Women are less likely to receive appropriate cardiovascular follow‐up and medication prescriptions after hospitalization for acute coronary syndromes. Despite these differences, the clinical outcomes for women remain comparable. These data suggest an opportunity to improve the posthospitalization management of cardiovascular disease regardless of sex.