bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for neuromuscular stimulation for rehabilitation after general and vascular surgery: a pilot randomised clinical study
Authors: Nimura Megumi , Lane Tristan , Rawashdeh Majd , Onida Sarah , Javed Azfar , Sritharan Ganan , Reese George , Hrouda David , Davies A H 
Published: February 2023

ObjectivesTo investigate the acceptability and safety of neuromuscular stimulation (NMES) as an adjunct for rehabilitation after vascular and general surgery.Methods and analysisProspective, single-centre, single-blind, parallel group, randomised controlled study. This study will be conducted in a single-centre, secondary care setting (National Healthcare Service Hospital) in the UK. All patients aged over 18 years undergoing vascular or general surgery with Rockwood Frailty Score of 3 or above on admission. Exclusion is inability or unwillingness to participate in trial, implanted electrical device, pregnancy and acute deep vein thrombosis. Target number of recruitment is 100. Participants will be randomly assigned to active NMES group (group A) or placebo NMES group (group B) prior to surgery. Participants will be blinded and asked to use the NMES device, 1–6 sessions daily (30 min per session) after surgery in addition to standard National Health Service rehabilitation care until discharge. The primary study outcomes are acceptability and safety of NMES assessed by the device satisfaction questionnaire on discharge and adverse events recorded during hospital stay. The secondary outcomes are the postoperative recovery and cost-effectiveness compared between two groups, assessed by various activity tests, mobility and independence measures and questionnaires.Ethics and disseminationEthical approvals were provided by London-Harrow Research Ethics Committee (REC) and the Health Research Authority (HRA), Ref: 21/PR/0250. Findings will be published in a peer-reviewed journal and presented at national and international conferences.Trial registration numberNCT04784962.
Multicentre, randomised, economic evaluation of a web-based interactive education platform, simple or enhanced, for patients with end-stage renal disease: the PIC-R trial protocol
Authors: Pillebout Evangeline , Durand-Zaleski Isabelle , Farge Louis , Perrier Lionel , de Chaisemartin Clement , Dupont J C K , Behaghel Luc , Rochaix Lise 
Published: February 2023

IntroductionEnd-stage renal disease (ESRD) affects 84 000 persons in France and costs an estimated €4.2 billion. Education about their disease empowers patients and allows improved management of their disease and better health outcomes. This study aims to explore whether the addition of an interactive web-based platform to patient education is effective and cost-effective and additionally whether complementing the platform with social functions and features improves its performance.Methods and analysisPatients with severe, ESRD or post-transplant will be randomised 1:1:1 to either standard therapeutic education; or education using a specific application; or the enhanced interactive app with social features. The total follow-up duration is 18 months. Primary endpoint is the cost utility of using app-based therapeutic intervention; secondary endpoints are: compliance with treatment guidelines, app use (professionals and patients), patients’ satisfaction, budget impact analysis.Ethics and disseminationThe findings will inform the deployment and reimbursement of the application. The study has ethical approval by the Ile de France ethics committee. Dissemination of the results will be presented at conferences and in peer-reviewed publications.Trial registration numberNCT03090828.
Protocol for estimating the willingness-to-pay-based value for a quality-adjusted life year to aid health technology assessment in India: a cross-sectional study
Authors: Chugh Yashika , Jyani Gaurav , Trivedi Mayur , Albert Sandra , Kar Sitanshu Sekhar , Patro Binod , Raman Swati , Rajsekar Kavitha , Baker Rachel Mairi , Donaldson Cam , Prinja Shankar 
Published: February 2023

IntroductionTo ensure that the evidence generated by health technology assessment (HTA) is translated to policy, it is important to generate a threshold value against which the outcomes of HTA studies can be compared. In this context, the present study delineates the methods that will be deployed to estimate such a value for India.Methods and analysisThe proposed study will deploy a multistage sampling approach considering economic and health status for selection of states, followed by selection of districts based on Multidimensional Poverty Index (MPI) and identification of primary sampling units (PSUs) using the 30-cluster approach. Further, households within PSU will be identified using systematic random sampling and block randomisation based on gender will be done to select respondent from the household. A total of 5410 respondents will be interviewed for the study. The interview schedule will comprise of three sections including background questionnaire to elicit socioeconomic and demographic characteristics, followed by assessment of health gains, and willingness to pay (WTP). To assess the health gains and corresponding WTP, the respondent will be presented with hypothetical health states. Using time trade off method, the respondent will indicate the amount of time he/she is willing to give up at the end of life to avoid morbidities in the hypothetical health condition. Further, respondents will be interviewed about their WTP for treatment of respective hypothetical conditions using contingent valuation technique. These estimates of health gains and corresponding WTP will then be combined to ascertain the value of WTP per quality-adjusted life year.Ethics and disseminationThe ethical approval has been obtained from the Institutional Ethics Committee (IEC) of Postgraduate Institute of Medical Education and Research, Chandigarh, India. The study outcomes will be made available for general use and interpretation of HTA studies commissioned by India’s central HTA Agency.
Paramedic supportive discharge programmes to improve health system efficiency and patient outcomes: a scoping review protocol
Authors: Goldstein Judah , Lajeunesse Dominic , Abawajy Khadija , Luan Angela , Hancock Kristy , Carter Alix , Greene Jennifer Anne , McVey Jen , Lee Jacques Simon 
Published: February 2023

IntroductionDischarging older adults with frailty home from the emergency department (ED) poses unique challenges due to multiple interacting physical and social problems. Paramedic supportive discharge services help overcome these challenges by adding in-home assessment and/or interventions. Our objective is to describe existing paramedic programmes designed to support discharge from the ED or hospital to avoid unnecessary hospital admissions. A comprehensive description of paramedic supportive discharge services will be conducted by mapping the literature to describe: (1) why such programmes are needed; (2) who is being targeted, making referrals and delivering the services and (3) what assessments and interventions are offered.Methods and analysisWe will include studies that focus on expanded paramedic roles (community paramedicine) and extended scope postdischarge from the ED or hospital. All study designs will be included with no limit by language. We will include peer-reviewed articles and preprints and a targeted search of grey literature from January 2000 to June 2022. The proposed scoping review will be conducted in accordance with the Joanna Briggs Institute methodology. We will use a search strategy designed by a health science librarian to search MEDLINE All (Ovid), CINAHL Full Text (EBSCO), Embase (Elsevier) and Scopus (Elsevier) for eligible studies from 2000 to present. Two independent reviewers will conduct screening and full-text review. Data extraction will be conducted by one reviewer and verified by another. We will report our findings descriptively by charting trends in the research.Ethics and disseminationResearch ethics review is not required as this is a scoping review comprised published studies. The results of this research will be published in a manuscript and presented at national and international geriatric and emergency medicine conferences. This research will inform future implementation studies on community paramedic supportive discharge services.RegistrationThis scoping review protocol was registered in Open Science Framework and can be found here:https://doi.org/10.17605/OSF.IO/X52P7.
Association of socioeconomic status with glycated haemoglobin level and risk factors for diabetic retinopathy: a cross-sectional study in Sichuan, western China
Authors: Xu Xinyin , Yang Wei , Deng Yin , Liu Lingling , Zhang Xin , Long Chengxu , Dong Ting , Zeng Jing , Kui Ji , Wu Xianping 
Published: February 2023

ObjectiveDiabetes affects 1 in 10 adults in China. Diabetic retinopathy (DR) is a diabetes-related complication that, if untreated, impairs vision and causes blindness. Evidence on DR diagnosis and risk factors is limited. This study aimed to add evidence from socioeconomic factors.DesignA cross-sectional survey of people with diabetes conducted in 2019 was analysed by using logistic regression to evaluate the association of socioeconomic factors with the glycated haemoglobin (HbA1c) level and DR.SettingFive counties/districts of western China (Sichuan) were included.ParticipantsRegistered participants with diabetes aged from 18 to 75 years were selected, and at last 2179 participants were included in the analysis.ResultsIn this cohort, 37.13% (adjusted value 36.52%), 19.78% (adjusted value 19.59%) and 17.37% of participants had HbA1c<7.0%, DR (24.96% of those in the high-HbA1c group) and non-proliferative DR, respectively. Participants with higher social health insurance coverage (urban employee insurance (UEI)), higher income and urban residents tended to have glycaemic control (HbA1c) compared with their counterparts (OR: 1.48, 1.08 and 1.39, respectively). Participants with UEI or higher income had a lower risk of DR (OR: 0.71 and 0.88, respectively); higher education was associated with a 53%–69% decreased risk of DR.ConclusionThis study shows disparities in the effect of socioeconomic factors on glycaemic (HbA1c) management and DR diagnosis among people with diabetes in Sichuan. Lower socioeconomic (especially non-UEI) status conferred a higher risk of high HbA1c and DR. The insights from this study indicate the need for national programmes to implement community-level measures to facilitate access to better HbA1c management and early detection of DR in patients with lower socioeconomic status and diabetes.Trial registration numberChinese Clinical Trial Registry (ChiCTR1800014432).
Couple-based lifestyle intervention to prevent type 2 diabetes: protocol for a randomised pilot trial
Authors: Whitaker Madelyn , Aguirre Monique C , Gutierrez Chavez Manuel , Beaulieu Elizabeth , Arones Yeny B , Gershenoff Dana , Hinton Kristie , Klein Natalie , Munezerou Uwizeye Jeanne , Napia Eru , Ramos Carmen , Tavake-Pasi O Fahina , Villalta Jeannette , Wolfsfeld Cathy , Witte Brieanne , Maxfield Ellen , Raphael Kalani , Simmons Debra L , Clark Lauren , Sher Tamara , Smith Timothy W , Baucom Katherine JW 
Published: February 2023

IntroductionType 2 diabetes is prevalent among US adults. Lifestyle interventions that modify health behaviours prevent or delay progression to diabetes among individuals at high risk. Despite the well-documented influence of individuals’ social context on their health, evidence-based type 2 diabetes prevention interventions do not systematically incorporate participants’ romantic partners. Involving partners of individuals at high risk for type 2 diabetes in primary prevention may improve engagement and outcomes of programmes. The randomised pilot trial protocol described in this manuscript will evaluate a couple-based lifestyle intervention to prevent type 2 diabetes. The objective of the trial is to describe the feasibility of the couple-based intervention and the study protocol to guide planning of a definitive randomised clinical trial (RCT).Methods and analysisWe used community-based participatory research principles to adapt an individual diabetes prevention curriculum for delivery to couples. This parallel two-arm pilot study will include 12 romantic couples in which at least one partner (ie, ‘target individual’) is at risk for type 2 diabetes. Couples will be randomised to either the 2021 version of the CDC’s PreventT2 curriculum designed for delivery to individuals (six couples), or PreventT2 Together, the adapted couple-based curriculum (six couples). Participants and interventionists will be unblinded, but research nurses collecting data will be blinded to treatment allocation. Feasibility of the couple-based intervention and the study protocol will be assessed using both quantitative and qualitative measures.Ethics and disseminationThis study has been approved by the University of Utah IRB (#143079). Findings will be shared with researchers through publications and presentations. We will collaborate with community partners to determine the optimal strategy for communicating findings to community members. Results will inform a subsequent definitive RCT.Trial registration numberNCT05695170
Continuous quality improvement strategy for increasing immediate postpartum long-acting reversible contraceptive use at Jimma University Medical Center, Jimma, Ethiopia
Authors: Sori Demisew Amenu , Debelew Gurmesa Tura , Degefa Lema Seboka , Asefa Zerihun 
Published: February 2023

BackgroundEven though the immediate postpartum period is a golden time and a great opportunity to provide long-acting reversible contraceptives to prevent unintended pregnancy, its utilisation is very low in Ethiopia. Quality of care in postpartum long-acting reversible contraceptive provision is thought to be an issue for this low utilisation. Thus, continuous quality improvement intervention is necessary to increase the use of postpartum long-acting reversible contraceptives at Jimma University Medical Center.MethodA quality improvement intervention to offer long-acting reversible contraceptive methods to immediate postpartum women at Jimma University Medical Center was initiated in June 2019. To study the baseline prevalence of long-acting reversible contraceptive use at Jimma Medical Centre over 8 weeks, we reviewed postpartum family planning registration logbooks and patients’ charts. Based on the baseline data, the quality gaps were identified, prioritised and change ideas were generated and tested over another 8 weeks towards achieving the immediate postpartum long-acting reversible contraceptive prevalence target set.ResultThis new intervention resulted in an average increase in immediate postpartum long-acting reversible contraceptive methods use from 6.9% to 25.4% by the end of the project intervention. The major barriers to low long-acting reversible contraceptive use were lack of attention from hospital administrative staff and quality improvement teams on the provision of long-acting reversible contraceptives, lack of training of healthcare providers on postpartum contraception and unavailability of contraception commodities at each postpartum service delivery points.Conclusion and recommendationsThe immediate postpartum long-acting reversible contraceptive use at Jimma Medical Centre was increased by training of healthcare providers, availing contraception commodities through administrative staff involvement, weekly audit and feedback on contraception use. Thus, training of the newly hired healthcare providers on postpartum contraception, involvement of hospital administrative staff, regular audits and feedback on contraception use is necessary to increase postpartum long-acting reversible contraception uptake.
PKR induces TGF-β and limits oncolytic immune therapy
Authors: Hong Bangxing , Sahu Upasana , Mullarkey Matthew P , Hong Evan , Pei Guangsheng , Yan Yuanqing , Otani Yoshihiro , Banasavadi-Siddegowda Yeshavanth , Fan Huihui , Zhao Zhongming , Yu Jianhua , Caligiuri Michael A , Kaur Balveen 
Published: February 2023

BackgroundMammalian cells have developed multiple intracellular mechanisms to defend against viral infections. These include RNA-activated protein kinase (PKR), cyclic GMP-AMP synthase and stimulation of interferon genes (cGAS-STING) and toll-like receptor-myeloid differentiation primary response 88 (TLR-MyD88). Among these, we identified that PKR presents the most formidable barrier to oncolytic herpes simplex virus (oHSV) replication in vitro.MethodsTo elucidate the impact of PKR on host responses to oncolytic therapy, we generated a novel oncolytic virus (oHSV-shPKR) which disables tumor intrinsic PKR signaling in infected tumor cells.ResultsAs anticipated, oHSV-shPKR resulted in suppression of innate antiviral immunity and improves virus spread and tumor cell lysis both in vitro and in vivo. Single cell RNA sequencing combined with cell-cell communication analysis uncovered a strong correlation between PKR activation and transforming growth factor beta (TGF-ß) immune suppressive signaling in both human and preclinical models. Using a murine PKR targeting oHSV, we found that in immune-competent mice this virus could rewire the tumor immune microenvironment to increase the activation of antigen presentation and enhance tumor antigen-specific CD8 T cell expansion and activity. Further, a single intratumoral injection of oHSV-shPKR significantly improved the survival of mice bearing orthotopic glioblastoma. To our knowledge, this is the first report to identify dual and opposing roles of PKR wherein PKR activates antivirus innate immunity and induces TGF-ß signaling to inhibit antitumor adaptive immune responses.ConclusionsThus, PKR represents the Achilles heel of oHSV therapy, restricting both viral replication and antitumor immunity, and an oncolytic virus that can target this pathway significantly improves response to virotherapy.
Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression
Authors: Khanna Dinesh , Maher Toby M , Volkmann Elizabeth R , Allanore Yannick , Smith Vanessa , Assassi Shervin , Kreuter Michael , Hoffmann-Vold Anna-Maria , Kuwana Masataka , Stock Christian , Alves Margarida , Sambevski Steven , Denton Christopher P 
Published: February 2023

ObjectiveTo investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC.MethodsThe SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (<18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15–40 or mRSS ≥18) at baseline.ResultsIn the placebo group, the rate of decline in FVC was numerically greater in subjects with <18 months since first non-Raynaud symptom (−167.8 mL/year), elevated inflammatory markers (−100.7 mL/year), mRSS 15–40 (−121.7 mL/year) or mRSS ≥18 (−131.7 mL/year) than in all subjects (−93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline.ConclusionIn the SENSCIS trial, subjects with SSc-ILD who had early SSc, elevated inflammatory markers or extensive skin fibrosis had a more rapid decline in FVC over 52 weeks than the overall trial population. Nintedanib had a numerically greater effect in patients with these risk factors for rapid ILD progression.
EVA1A (Eva-1 Homolog A) Promotes Endothelial Apoptosis and Inflammatory Activation Under Disturbed Flow Via Regulation of Autophagy
Authors: Canham Lindsay , Sendac Sam , Diagbouga Mannekomba R. , Wolodimeroff Elena , Pirri Daniela , Tardajos Ayllon Blanca , Feng Shuang , Souilhol Celine , Chico Timothy J.A. , Evans Paul C. , Serbanovic-Canic Jovana 
Published: February 2023

Background:
Hemodynamic wall shear stress (WSS) exerted on the endothelium by flowing blood determines the spatial distribution of atherosclerotic lesions. Disturbed flow (DF) with a low WSS magnitude and reversing direction promotes atherosclerosis by regulating endothelial cell (EC) viability and function, whereas un-DF which is unidirectional and of high WSS magnitude is atheroprotective. Here, we study the role of EVA1A (eva-1 homolog A), a lysosome and endoplasmic reticulum-associated protein linked to autophagy and apoptosis, in WSS-regulated EC dysfunction.

Methods:
The effect of WSS on EVA1A expression was studied using porcine and mouse aortas and cultured human ECs exposed to flow. EVA1A was silenced in vitro in human ECs and in vivo in zebrafish using siRNA (small interfering RNA) and morpholinos, respectively.

Results:

EVA1A was induced by proatherogenic DF at both mRNA and protein levels.
EVA1A
silencing resulted in decreased EC apoptosis, permeability, and expression of inflammatory markers under DF. Assessment of autophagic flux using the autolysosome inhibitor, bafilomycin coupled to the autophagy markers LC3-II (microtubule-associated protein 1 light chain 3-II) and p62, revealed that
EVA1A
knockdown promotes autophagy when ECs are exposed to DF, but not un-DF . Blocking autophagic flux led to increased EC apoptosis in
EVA1A
-knockdown cells exposed to DF, suggesting that autophagy mediates the effects of DF on EC dysfunction. Mechanistically,
EVA1A
expression was regulated by flow direction via TWIST1 (twist basic helix-loop-helix transcription factor 1). In vivo, knockdown of
EVA1A
orthologue in zebrafish resulted in reduced EC apoptosis, confirming the proapoptotic role of EVA1A in the endothelium.

Conclusions:
We identified EVA1A as a novel flow-sensitive gene that mediates the effects of proatherogenic DF on EC dysfunction by regulating autophagy.
Capacity for LDL (Low-Density Lipoprotein) Retention Predicts the Course of Atherogenesis in the Murine Aortic Arch
Authors: Lewis Esmeralda A. , Muñiz-Anquela Rocío , Redondo-Angulo Ibon , González-Cintado Leticia , Labrador-Cantarero Verónica , Bentzon Jacob F. 
Published: February 2023

Background:
To cause atherosclerosis, LDLs (low-density lipoproteins) must first pass through the endothelium and then become retained in the arterial matrix. Which of these two processes is rate-limiting and predicts the topography of plaque formation remains controversial. To investigate this issue, we performed high-resolution mapping of LDL entry and retention in murine aortic arches before and during atherosclerosis development.

Methods:
Maps of LDL entry and retention were created by injecting fluorescently labeled LDL followed by near-infrared scanning and whole-mount confocal microscopy after 1 hour (entry) and 18 hours (retention). By comparing arches between normal mice and mice with short-term hypercholesterolemia, we analyzed changes in LDL entry and retention during the LDL accumulation phase that precedes plaque formation. Experiments were designed to secure equal plasma clearance of labeled LDL in both conditions.

Results:
We found that LDL retention is the overall limiting factor for LDL accumulation but that the capacity for LDL retention varied substantially over surprisingly short distances. The inner curvature region, previously considered a homogenous atherosclerosis-prone region, consisted of dorsal and ventral zones with high capacity and a central zone with low capacity for continued LDL retention. These features predicted the temporal pattern of atherosclerosis, which first appeared in the border zones and later in the central zone. The limit to LDL retention in the central zone was intrinsic to the arterial wall, possibly caused by saturation of the binding mechanism, and was lost upon conversion to atherosclerotic lesions.

Conclusions:
Capacity for continued LDL retention varies over short distances and predicts where and when atherosclerosis develops in the mouse aortic arch.