bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring heterogeneity in coxarthrosis medication use patterns before total hip replacement: a State Sequence Analysis
Authors: Novelli Anna , Frank-Tewaag Julia , Franke Sebastian , Weigl Martin , Sundmacher Leonie 
Published: September 2024

ObjectiveEvidence of geographical variation in total hip replacement (THR) and deviations from treatment guidelines persists. In this exploratory study, we aim to gain an in-depth understanding of patients’ healthcare trajectories by identifying and visualising medication use patterns in coxarthrosis patients before surgery. We examine their association with patient characteristics and THR, and compare them with recommendations on mild analgesics, opioid prescription and exhaustion of conservative therapy.MethodsIn this exploratory study, we apply State Sequence Analysis (SSA) on German health insurance data (2012–2015). We analyse a cohort of coxarthrosis patients, half of whom underwent THR after a 1 year observation period and half of whom did not undergo surgery until at least 1 year after the observation period. Hierarchical states are defined based on prescriptions. We construct sequences, calculate sequence similarity using optimal matching and identify medication use patterns via clustering. Patterns are visualised, descriptive statistics are presented and logistic regression is employed to investigate the association of medication patterns with subsequent THR.ResultsSeven distinct medication use patterns are identified, correlating strongly with patient characteristics and subsequent THR. Two patterns leading to THR demonstrate exhaustion of pharmacological therapy. Opioid use is concentrated in two small patterns with low odds for THR. The most frequent pattern lacks significant pharmacological therapy.ConclusionsThis SSA uncovers heterogeneity in medication use patterns before surgery in coxarthrosis patients. Cautious opioid handling and adherence to a stepped prescription approach are observed, but many patients display low medication therapy usage and lack evidence of exhausting conservative options before surgery.
Qualitative interview study of patient-reported symptoms, impacts and treatment goals of patients with obstructive hypertrophic cardiomyopathy
Authors: Shore Supriya , Ervin Claire , Kosa Katherine , Fehnel Sheri , Salberg Lisa , Butzner Michael , Heitner Stephen B , Jacoby Daniel , Saberi Sara 
Published: September 2024

ObjectiveHypertrophic cardiomyopathy (HCM), including obstructive HCM (oHCM), is the most common inherited cardiomyopathy causing lifestyle-limiting symptoms. Data are lacking about patients’ perspectives on the daily impact of their symptoms. This qualitative interview study was conducted to better understand patients’ experiences with oHCM.MethodsIn October 2019, telephone interviews were conducted with 20 US adults with oHCM identified by the Hypertrophic Cardiomyopathy Association. Using a semi-structured interview guide, key symptoms, impacts of oHCM and oHCM treatment goals were discussed.ResultsMedian age was 54 years (range 29–78), 55% were women, 85% were white and 15% were Hispanic or Latino. Median time since diagnosis was 3 years. Symptoms included shortness of breath, dizziness/light-headedness, heart palpitations/fluttering (all 95%), fatigue (90%) and chest pain/pressure (80%). All participants reported limitations in physical functioning/activities; most reported additional impacts (emotional stress (80%), fear of dying (55%)). Shortness of breath and fatigue were among their most bothersome symptoms; an effective oHCM treatment would need to improve ≥1 of these symptoms (allowing increased physical/social activity).ConclusionsPatients with oHCM experience a high symptom burden and psychosocial impacts, affecting health status. Improved shortness of breath, fatigue and physical functioning are highly valued by patients and represent important treatment goals.
Risky sexual behaviour and its determinants among undergraduate students residing in hostels of Kathmandu Metropolitan City, Nepal: a cross-sectional study
Authors: Chaudhary Ram Kumar , Chalise Anisha , Pandey Saloni , Paudel Shishir 
Published: September 2024

ObjectivesTo assess the prevalence of risky sexual behaviour (RSB) and its associated factors among Nepalese undergraduates residing in hostels of Kathmandu Metropolitan City, Nepal.DesignCross-sectional studySettingHostels operating inside Kathmandu Metropolitan City were taken as the study setting.ParticipantA total of 361 undergraduate students residing in hostels in the Metropolitan CityOutcome measuresRSB was the outcome measure assessed using nine questions able to trace any risky sexual practice practiced by the participants within the past year prior to data collection. The question included participants’ engagement in sexual activity before the age of consent, having unprotected vaginal sex even when pregnancy is not intended, engaging in vaginal sex with strangers without a condom, risky oral sex with a stranger and/or intimate partner, risky condom use, having multiple sex partners, having sex under the influence of alcohol and having sex with commercial sex workers. A positive response to any of these nine questions was considered indicative of RSB. Pearson’s χ2test and multivariable logistic regression analysis were performed to determine factors associated with RSB at the 5% level of significance.ResultsThe prevalence of RSB was found to be 35.7% (95% CI: 30.2 to 40.2). RSB was found to be associated with higher age (≥25 years) (aOR: 3.938; 95% CI: 1.707 to 8.673), male gender (aOR: 3.233; 95% CI: 1.623 to 6.439), being in relationships in the past/current (aOR: 3.914, 95% CI: 2.099 to 7.012), lower education of mother (aOR: 3.655; 95% CI: 1.189 to 9.237) and peer pressure to have a sexual relationship (aOR: 2.356; 95% CI: 1.260 to 4.349). Notably, bivariate analysis illustrated problematic pornographic consumption to have a statistical relation with RSB, which was weakened and became non-significant after accounting for other factors in the adjusted model (aOR:1.213, 95% CI: 0.331 to 4.442).ConclusionRSB is a concerning behaviour among undergraduate students and is linked with age, gender, relationship status, parental education and peer pressure. There is a need for comprehensive sex education programmes that equip students with the knowledge and skills needed to navigate healthy relationships, make safe choices and embrace responsible sexual practices.
Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial
Authors: Cirnigliaro Christopher M , Kuo William , Forrest Gail F , Spungen Ann M , Parrott J Scott , Cardozo Christopher P , Pal Saikat , Bauman William A 
Published: September 2024

IntroductionPersons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that is directly associated with increased risk of long-bone fractures. There is a paucity of research that has successfully implemented rehabilitation and/or exercise training interventions to mitigate bone loss after acute SCI or reverse bone loss that has already occurred in chronic SCI. This paper describes a research protocol to compare the effect of exoskeletal-assisted walking (EAW) alone versus EAW plus transcutaneous spinal cord stimulation (EAW+tSCS) on bone density, geometry and strength in a cohort of chronic SCI participants.Methods and analysisAfter meeting eligibility criteria and completing baseline testing, sixteen participants will be block randomised into the EAW alone group or the EAW+tSCS combined group (n=8 each group). Each group will receive a total of 108 overground training sessions (60 min sessions, 3 times a week, for 36 weeks) for the 9-month training period. Imaging for bone density and geometry by dual-energy X-ray absorptiometry and peripheral quantitative CT will be performed prior to starting the intervention (baseline), after 72 training sessions, and again after 108 sessions in each of the intervention arms. CT imaging of both lower extremities will be performed at baseline and at the 9-month time point in each of the intervention arms. Finite element models of bone loading will be generated based on three-dimensional (3D) reconstruction of bone architecture from CT imaging prior to and 9 months after the intervention.Ethics and disseminationThis study is currently approved by the Kessler Foundation and James J. Peters VA Medical Center Institutional Review Board. A member of the research team will review and explain the study consent form and will have all eligible participants sign prior to participation in the study. Results from this study will be disseminated to clinicians and researchers in the SCI community at national and international conferences.Trial registration numberNCT03096197.
Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022
Authors: Goldstein Cory E , Marouf Yacine , Johri Mira , Shaw Julia F , Sergeant Anand , Nicholls Stuart G , Althabe Fernando , Ferrand Rashida A , van der Graaf Rieke , Hemming Karla , Mbuagbaw Lawrence , Treweek Shaun , Welch Vivian A , Weijer Charles , Taljaard Monica 
Published: September 2024

ObjectiveCluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time.DesignA systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews.Data sourcesWe searched MEDLINE between 1 January 2017 and 17 August 2022.Eligibility criteria for selecting studiesWe included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022.Data extraction and synthesisData were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country’s economic level or publication year.ResultsAmong 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country’s economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time.ConclusionOur findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed.
Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first in patient, randomised, double-blind, phase I/II study in systemic lupus erythematosus
Authors: Tanaka Yoshiya , Kumanogoh Atsushi , Atsumi Tatsuya , Ishii Tomonori , Tago Fumitoshi , Aoki Mari , Yamamuro Shintaro , Akira Shizuo 
Published: September 2024

ObjectivesTo evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I/II study in patients with systemic lupus erythematosus (SLE).MethodsTwo sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200 mg; n=8 or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker.ResultsThe proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% (3/8 patients) for 100 mg; 77.8% (7/9 patients) for 200 mg) and 66.7% (6/9 patients) in the placebo group. No Common Terminology Criteria for Adverse Events≥Grade 3 TEAEs occurred. PK parameters were similar to these in previous phase I studies in healthy adults. The IGS and levels of proinflammatory cytokines after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. The response rate of the British Isles Lupus Assessment Group-based Composite Lupus Assessment at week 12 was 37.5% (3/8 patients) for E6742 100 mg, 57.1% (4/7 patients) for E6742 200 mg and 33.3% (3/9 patients) for placebo group.ConclusionsE6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.Trial registration numberNCT05278663.
Stimulus-dependent spiking and bursting behavior in memsensor circuits: experiment and wave digital modeling
Authors: Jenderny Sebastian , Gupta Rohit , Madurawala Roshani , Strunskus Thomas , Faupel Franz , Kaps Sören , Adelung Rainer , Ochs Karlheinz , Vahl Alexander 
Published: September 2024

Abstract
Biological information processing pathways in neuron assemblies rely on spike activity, encoding information in the time domain, and operating the highly parallel network at an outstanding robustness and efficiency. One particularly important aspect is the distributed, local pre-processing effectively converting stimulus-induced signals to action potentials, temporally encoding analog information. The field of brain-inspired electronics strives to adapt concepts of information processing in neural networks, e.g., stimulus detection and processing being intertwined. As such, stimulus-modulated resistive switching in memristive devices attracts an increasing attention. This work reports on a three-component memsensor circuit, featuring a UV-sensor, a memristive device with diffusive switching characteristics and a capacitor. Upon application of a DC bias, complex, stimulus-dependent spiking and brain-inspired bursting can be observed, as experimentally showcased using combination of a microstructured, tetrapodal ZnO sensor and a Au/SiOxNy/Ag cross-point memristive device. The experimental findings are corroborated by a wave digital model, which successfully replicates both types of behavior and outlines the relation of temporal variation of switching thresholds to the occurrence of bursting activity.

Graphical abstract
Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer
Authors: Cui Chengying , Zhang Haojie , Yang Congcong , Yin Mingwei , Teng Xinkun , Yang Miaomiao , Kong Dejie , Zhang Jinzhi , Peng Weidong , Chu Zhimin , Wang Jingjing , Sun Yating , Kang Liping , Lyu Bin , Gao Qian , Wu Mingqing , Wang Yongqiang , Li Yang 
Published: September 2024

Abstract
Currently, only 20% to 40% of patients with cancer benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunologic landscape during treatment are critical for improving responsiveness to immunotherapy. In this study, we identified JNK signaling in cancer-associated fibroblasts (CAF) as a regulator of the immunosuppressive TME. Single-cell RNA sequencing of bladder cancer samples treated with a JNK inhibitor revealed enhanced cytotoxicity and effector functions of CD8+ T cells. In untreated tumors, CAFs interacted frequently with CD8+ T cells and mediated their exhaustion. JNK inhibition abrogated the immunosuppression function of CAFs by downregulating the expression of thymic stromal lymphopoietin (TSLP), thereby restoring CD8+ T-cell cytotoxicity. In addition, blockade of CAF-derived TSLP in combination with anti–PD-1 treatment promoted tumor elimination by CD8+ T cells in vivo. Collectively, these results indicate that JNK signaling plays an important immunosuppressive role in the TME by promoting expression of TSLP in CAFs and suggest that inhibiting JNK signaling could be a promising immunotherapeutic strategy for cancer treatment.
Significance: JNK signaling promotes the secretion of TSLP by bladder cancer–associated fibroblasts to impede CD8+ T-cell activity, which can be circumvented by combination treatment targeting JNK signaling and PD-1.
The Role of Residential Segregation in Treatment and Outcomes of Ductal Carcinoma In Situ of the Breast
Authors: Nabi Oumarou , Liu Ying , Struthers James , Lian Min 
Published: September 2024

Abstract

Background:
It remains unclear whether residential segregation impacts on clinical treatment and outcomes for ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer (IBC).

Methods:
This population-based retrospective cohort study included adult non-Hispanic White and Black women diagnosed with unilateral DCIS between January 1990 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the Index of Concentration at the Extremes. Multilevel logistic regression and Cox proportional hazards regression accounting for county-level clustering were used to estimate the ORs of local treatment and HRs of subsequent IBC and mortality.

Results:
Of 103,898 cases, mean age was 59.5 years, 12.5% were non-Hispanic Black, 87.5% were non-Hispanic White, 97.5% underwent surgery, 64.5% received radiotherapy following breast-conserving surgery (BCS), 7.1% developed IBC, and 18.6% died from all causes. Among women living in the least versus most privileged counties, we observed higher odds of receiving mastectomy [vs. BCS; OR = 1.51; 95% confidence interval (CI), 1.35–1.69; Ptrend &lt; 0.001] and radiotherapy following BCS(OR = 1.27; 95% CI, 1.07–1.51; Ptrend &lt; 0.01); the risk was higher in subsequent ipsilateral IBC (HR = 1.16; 95% CI, 1.02–1.32; Ptrend = 0.04), not in breast cancer–specific mortality (HR = 1.04; 95% CI, 0.88–1.23; Ptrend = 0.56).

Conclusions:
The results provide evidence for disparities in clinical treatment for DCIS and prognostic outcomes among women in racially and economically segregated counties.

Impact:
Our findings may inform geographically targeted multilevel interventions to reduce breast cancer burden and improve breast cancer care and equity.
Serum Soluble Corin and Long‐Term Clinical Outcomes After Acute Ischemic Stroke
Authors: Wang Aili , Zhai Yujia , Zhang Jin , Che Bizhong , Zheng Xiaowei , Peng Yanbo , Xu Tan , He Jiang , Zhang Yonghong , Zhong Chongke 
Published: September 2024

Background
Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long‐term clinical outcomes after acute ischemic stroke.

Methods and Results

We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all‐cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log‐corin was associated with a 21% (95% CI, 11–30), 16% (95% CI, 6–26), and 12% (95% CI, 3–21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all‐cause mortality and cardiovascular events, as shown by C‐statistics (all
P
<0.05).

Conclusions
Serum soluble corin was associated with decreased risks of long‐term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.
Atrial Fibrillation Status and Physical Rehabilitation in Older Patients With Acute Decompensated Heart Failure: An Analysis From the REHAB‐HF Trial
Authors: Corsi Douglas R. , Dikdan Sean , Upadhyay Naman , Chen Haiying , Kitzman Dalane W. , Mentz Robert , Whellan David J. , Frisch Daniel R. 
Published: September 2024

Background
The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial demonstrated that a transitional, tailored, progressive rehabilitation intervention improved physical function, 6‐minute walk distance, frailty, quality‐of‐life, and depression in older patients hospitalized for acute decompensated heart failure. This analysis assessed the impact of atrial fibrillation (AF) on intervention benefits.

Methods and Results

Of 349 enrolled patients hospitalized for acute decompensated heart failure (mean age 72.7±8.1 years), 176 (50.4%) had AF. Participants were randomly assigned to 12‐week rehabilitation intervention or attention control. The primary outcome was Short Physical Performance Battery score at 3 months. Participants with AF were older (74.4±8.3 versus 70.8±7.5,
P
<0.0001) and had higher prevalence of heart failure with preserved ejection fraction (58.5% versus 47.4%,
P
=0.037). Patients with and without AF had similar improvement in Short Physical Performance Battery score (mean difference between rehabilitation intervention and attention control, 1.5 [95% CI, 0.6–2.3] versus 1.5 [95% CI, 0.7–2.3];
P
<0.001). Those with AF had significant improvement in 6‐minute walk distance (all
P
<0.05) and each of the Short Physical Performance Battery domains: balance, 4‐meter walk, and chair rise. Kansas City Cardiomyopathy Questionnaire score significantly improved in patients with AF (
P
<0.05) but not those without AF (
P
>0.05). Interaction
P
values for 3‐month outcomes by AF status were not significant (
P
>0.1). No significant differences were observed in deaths, all‐cause rehospitalizations, or heart failure hospitalizations at 6 months.

Conclusions
In older, hospitalized patients with acute decompensated heart failure, the presence of AF did not significantly affect the benefit of the rehabilitation intervention on physical function and quality of life. The intervention appears safe and effective regardless of AF status.

Registration

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT02196038.