bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the development of a framework of social accountability standards for healthcare service delivery: a qualitative multipart, multimethods process
Authors: Anawati Alex , Cameron Erin , Harvey Jacqueline 
Published: September 2023

ObjectivesSocial accountability is an equity-oriented health policy strategy that requires institutions to focus on local population needs. This strategy is well established in health professional education, but there is limited understanding of its application in healthcare service delivery. Building on what is known in the education setting, this study aimed to explore the development of a framework of comprehensive, evidence-based social accountability standards for healthcare service delivery institutions.DesignThis qualitative, multipart, multimethods study consisted of a modified Delphi process guided by an evidence-based social accountability tool for health professional education and complementary methods including developmental evaluation and a review of select literature to capture emerging evidence and contextual relevance.SettingThe study took place in Northern Ontario, Canada at a medical school and a tertiary, regional academic health sciences centre that are both grounded in social accountability.ParticipantsEight expert participants from diverse, multidisciplinary backgrounds, including a patient advocate, were purposefully recruited from both institutions, enrolled and seven completed the study.Main outcomeThe resulting framework of social accountability standards is organised into 4 major sections that capture broad and critical concepts; 17 key component reflective questions that address key themes; 39 aspirations that describe objective standards and 197 indicators linked to specific expectations.ResultsThree modified Delphi rounds were completed producing a framework of consensus derived standards. Developmental evaluation helped identify facilitators, barriers and provided real-time feedback to the study’s processes and content. The literature reviewed identified 10 new concepts and 43 amendments.ConclusionThis study highlights the development of a comprehensive, evidence-based framework of social accountability standards for healthcare service delivery institutions. Future studies will aim to evaluate the application of these standards to guide equity-oriented social accountability health policy strategies in healthcare service delivery.
Effect of exoskeleton robot-assisted training on gait function in chronic stroke survivors: a systematic review of randomised controlled trials
Authors: Yang Jinchao , Gong Yu , Yu Lei , Peng Laiying , Cui Yuanfen , Huang Hailong 
Published: September 2023

ObjectivesNumbers of research have reported the usage of robot-assisted gait training for walking restoration post-stroke. However, no consistent conclusion has been reached yet about the efficacy of exoskeleton robot-assisted training (ERAT) on gait function of stroke survivors, especially during the chronic period. We conducted a systematic review to investigate the efficacy of ERAT on gait function for chronic stroke survivors.DesignThis review followed the Participant, Intervention, Comparison and Outcome principle.Data sourcesPubMed, Cochrane Library, Web of Science, Embase and Cumulative Index to Nursing and Allied Health Literature databases were systematically searched until December 2022.Eligibility criteriaOnly randomised controlled trials (RCTs) were included and these RCTs took patients who had a chronic stroke as participants, exoskeleton robot-assisted gait training as intervention, regular rehabilitation therapy as comparison and gait-related functional assessments as outcomes.Data extraction and synthesisData extraction and synthesis used the reporting checklist for systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The risk of bias and methodological quality of included studies were evaluated by two independent investigators under the guidance of Cochrane risk of bias.ResultsOut of 278 studies, a total of 10 studies (n=323, mean age 57.6 years, 63.2% males) were identified in this systematic review. According to the Cochrane risk of bias, the quality of these studies was assessed as low risk. Six studies reported favourable effects of ERAT on gait function involving gait performance, balance function and physical endurance, and the ERAT group was significantly superior when compared with the control group. In contrast, the other four trials showed equal or negative effects of ERAT considering different study designs. All the included studies did not claim any serious adverse events.ConclusionERAT could be an efficient intervention to improve gait function for individuals who had a chronic stroke. However, more rigorously designed trials are required to draw more solid evidence.PROSPERO registration numberCRD42023410796.
Protocol for a 2-year longitudinal study of eating disturbances, mental health problems and overuse injuries in rock climbers (CLIMB)
Authors: Edlund Klara , Nigicser Isabel , Sansone Mikael , Identeg Fredrik , Hedelin Henrik , Forsberg Niklas , Tranaeus Ulrika 
Published: September 2023

IntroductionRock climbing is a rapidly growing sport in which performance may be affected by participant’s weight and leanness, and there may be pressure on athletes with respect to their eating behaviour and body weight. However, there is sparse research performed on climbers, constituting a knowledge gap which the present study aims to fill. The primary outcomes of the study are to examine disordered eating and overuse injuries in rock climbers. Secondary variables are body image, indicators of relative energy deficiency, mental health problems, compulsive training, perfectionism, sleep quality and bone density.Method and analysisThis prospective longitudinal study aims to recruit Swedish competitive rock climbers (>13 years) via the Swedish Climbing Federation. A non-athlete control group will be recruited via social media (n=equal of the climbing group). Data will be collected using streamlined validated web-based questionnaires with three follow-ups over 2 years. Inclusion criteria for rock climbers will be a minimum advanced level according to International Rock-Climbing Research Association. The non-athlete control group is matched for age and gender. Exclusion criteria are having competed at an elite level in any sport as well as training more often than twice per week. Statistical analyses will include multinominal logistic regression, multivariate analysis of variance (MANOVA) and structural equation modelling (SEM). We will assess effect measure modification when relevant and conduct sensitivity analyses to assess the impact of lost to follow-up.Ethics and disseminationThe Rock-Climbers’ Longitudinal attitudes towards Injuries, Mental health and Body image study, CLIMB, was approved by the Swedish ethics authority (2021-05557-01). Results will be disseminated through peer-reviewed research papers, reports, research conferences, student theses and stakeholder communications.Trial registration numberNCT05587270.
Use of virtual reality in port implantation to reduce perioperative anxiety and pain: protocol for a randomised controlled pilot trial at a single German university hospital (VIP-trial; DRKS00028508)
Authors: Graf Sandra , Feldmann Hannah , Hunold Lisa S , Steinkraus Kira C , Nasir Nadir , Michalski Christoph W , Dörr-Harim Colette , Hüttner Felix J 
Published: September 2023

IntroductionIntravenous access port implantation is commonly performed under local anaesthesia, which offers advantages such as increased patient satisfaction and resource savings compared with general anaesthesia. However, patients may experience increased perioperative stress and anxiety in the operating room setting without general anaesthesia. Virtual reality (VR) distraction or hypnosis during surgery under local anaesthesia may help patients to auditorily and visually separate from their real environment and engage with a virtual environment through hypnorelaxing guidance. Previous studies suggested that VR hypnosedation may reduce the use of sedatives or general anaesthesia, and may offer additional benefits such as reducing postoperative pain and nausea, and promoting faster patient discharge.Methods and analysisThe VIP trial is a randomised controlled pilot trial comparing the usage of VR during port implantation with the current standard of care (local anaesthesia and analgosedation if needed). A total of 120 adult patients are included after screening for eligibility and obtaining informed consent. Patients are randomised preoperatively in a 1:1 ratio to the trial groups. The main outcomes are change of perioperative anxiety and pain. Further outcomes include patient satisfaction and tolerability, perioperative analgesia and sedation, occurrence of postoperative nausea, vomiting and VR sickness symptoms, surgeon’s satisfaction, procedure duration, postoperative complications until postoperative day 30 and patient willingness to hypothetically undergo port implantation again under the same conditions.Ethics and disseminationThe VIP trial has been approved by the Ethics Committee of the Medical Faculty of Ulm University (reference number 03/22). If the intervention demonstrates that VR can effectively reduce perioperative anxiety and pain, it may become a novel standard of care to minimise the need for analgosedation or general anaesthesia in port implantation procedures and improve patient outcomes. The results will be submitted to a peer-reviewed journal in the field and will be presented at applicable conferences to ensure rigorous evaluation and access for the academic community.Trial registration numberGerman Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275-4995.
Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial
Authors: Ma Shaolei , Li Cong , Gao Zhiwei , Xie Jianfeng , Qiu Haibo , Yang Yi , Liu Ling 
Published: September 2023

IntroductionSepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate into the lung, eventually leading to the occurrence of ARDS. Sivelestat sodium is an NE inhibitor that can inhibit the inflammatory reaction during systemic inflammatory response syndrome and alleviate lung injury. Therefore, we hypothesise that intravenous sivelestat sodium may prevent the occurrence of ARDS in patients with sepsis.Methods and analysisThis is a prospective, investigator-initiated, double-blind, adaptive, multicentre, randomised, controlled clinical trial with an adaptive ‘sample size re-estimation’ design. Patients meeting the inclusion criteria who were transferred into the intensive care unit will be randomly assigned to receive sivelestat sodium or placebo for up to 7 days. The primary outcome is the development of ARDS within 7 days after randomisation. A total of 238 patients will be recruited based on a 15% decrease in the incidence of ARDS in the intervention group in this study. A predefined interim analysis will be performed to ensure that the calculation is reasonable after reaching 50% (120) of the planned sample size.Ethics and disseminationThe study protocol was approved by the Ethics Committee of ZhongDa Hospital affiliated to Southeast University (identifier: Clinical Ethical Approval No. 2021ZDSYLL153-P03). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences and meetings.Trial registration numberNCT04973670.
Time to recovery and its predictors among under five children in outpatient therapeutic feeding programme in Borena zone, Southern Ethiopia: a retrospective cohort study
Authors: Kitesa Gutu Yonas , Berhe Trhas Tadesse , Tedla Getachew Weldeyohannes , Sahile Addisu Tadesse , Abegaz Kedir Hussein , Shama Adisu Tafari 
Published: September 2023

ObjectivesThis study aimed to assess the time to recovery and its predictors among 6–59 months aged children treated at an outpatient therapeutic feeding programme in Borena zone.DesignA retrospective cohort study.SettingFacility based; 23 treatment sites included in this study.ParticipantsAmong the cohorts of 601 children aged 6–59 months enrolled from July 2019 to June 2021, records of 590 children were selected using systematic random sampling. Transfers and incomplete records were excluded.Primary and secondary outcome measuresTime to recovery was a main outcome while its predictors were secondary outcomes.ResultsThe median recovery time was 49 days (95% CI=49 to 52) with a recovery rate of 79.8% (95% CI=76.4 to 83.0). Absence of comorbidity (adjusted HR, AHR=1.72, 95% CI=1.08 to 2.73), referral way by trained mothers on screening (AHR=1.91, 95% CI=1.25 to 2.91), new admission (AHR=1.59, 95% CI=1.05 to 2.41) and adequate Plumpy’Nut provision (AHR=2.10, 95% CI=1.72 to 2.56) were significantly associated with time to recovery. It is also found that being from a distance ≥30 min to treatment site lowers a chance of recovery by 27% (AHR=0.73, 95% CI=0.60 to 0.89).ConclusionsThe findings showed that a time to recovery was within an acceptable range. Incidence of recovery is enhanced with early case detection, proper management, nearby service, new admissions, provision of adequate Plumpy’Nut and enabling mothers to screen their own children for acute malnutrition. However, we did not observe a statistically significant association among breastfeeding status, type of health facility, wasting type, vaccination and routine medications. Service providers should improve adherence to treatment protocols, defaulter tracing, community outreach and timely case identification.
Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer
Authors: van Eijck Casper W F , Mustafa Dana A M , Vadgama Disha , de Miranda Noel F C C , Groot Koerkamp Bas , van Tienhoven Geertjan , van der Burg Sjoerd H , Malats Núria , van Eijck Casper H J 
Published: September 2023

BackgroundThis study investigates sex disparities in clinical outcomes and tumour immune profiles in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection preceded by gemcitabine-based neoadjuvant chemoradiotherapy (nCRT).MethodsPatients originated from the PREOPANC randomised controlled trial. Upfront surgery was performed in 82 patients, and 66 received nCRT before resection. The impact of sex on overall survival (OS) was investigated using Cox proportional hazards models. The immunological landscape within the tumour microenvironment (TME) was mapped using transcriptomic and spatial proteomic profiling.ResultsThe 5-year OS rate differed between the sexes following resection preceded by nCRT, with 43% for women compared with 22% for men. In multivariate analysis, the female sex was a favourable independent prognostic factor for OS only in the nCRT group (HR 0.19; 95% CI 0.07 to 0.52). Multivariate heterogeneous treatment effects analysis revealed a significant interaction between sex and treatment, implying increased nCRT efficacy among women with resected PDAC. The TME of women contained fewer protumoural CD163+MRC1+M2 macrophages than that of men after nCRT, as indicated by transcriptomic and validated using spatial proteomic profiling.ConclusionPDAC tumours of women are more sensitive to gemcitabine-based nCRT, resulting in longer OS after resection compared with men. This may be due to enhanced immunity impeding the infiltration of protumoral M2 macrophages into the TME. Our findings highlight the importance of considering sex disparities and mitigating immunosuppressive macrophage polarisation for personalised PDAC treatment.
Droplet digital PCR (ddPCR) using FFPE DNA to assess methylation status ofMGMTgene among patients withIDHmutant astrocytoma andIDHwild-type glioblastoma
Authors: Abarna Rajadurai , J Ranjani , chacko Geeta , Pai Rekha 
Published: September 2023

MGMTpromoter methylation analysis in formalin-fixed paraffin-embedded (FFPE) tissues can be challenging since the DNA obtained is often fragmented. Bisulfite conversion, which is essential to determine methylation status, further degrades DNA. While conventional methylation-specific PCR (MSP) and pyrosequencing assays have long been used to determine the methylation status ofMGMT, this study was designed to determine the utility of one-tube DNA extraction method coupled with a droplet digital PCR (ddPCR) assay, to study the epigenetic changes in the promoter region of theMGMTgene using DNA obtained from FFPE.The FFPE blocks of 30 (n=30) patients with Central Nervous System (CNS) WHO grade 4 tumours, previously tested by MSP (2011–2021) were retrieved; DNA was extracted using one-tube extraction method and bisulfite converted. All converted samples were analyzed for methylation status of theMGMTpromoter region with a laboratory designed Methylation-Specific ddPCR (MS ddPCR) using degenerate primers and probes that were labelled with FAM or HEX flurocein dye.Of the 30 cases, 20 cases wereMGMTmethylated and 10 cases were unmethylated by MS ddPCR. The results of MS ddPCR were then compared with those obtained by MSP and found to be concordant in 93.3% (28/30) of the cases and discordant in 2 cases. The Cohen’s kappa coefficient (κ) was 0.84. The sensitivity, specificity, positive predictive value and negative predictive value of the assay in detecting the methylation status was found to be 95%, 90%, 95% and 90%.The results show that MS ddPCR is a valuable tool to detect the methylation status of MGMT in FFPE with high sensitivity. This method is cost-effective and easy to perform and could be an attractive alternative to the routine method of MSP.
AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival
Authors: Mehra Vedika , Agliardi Giulia , Dias Alves Pinto Juliana , Shafat Manar S , Garai Amaia Cadinanos , Green Louisa , Hotblack Alastair , Arce Vargas Fred , Peggs Karl S , van der Waart Anniek B , Dolstra Harry , Pule Martin A , Roddie Claire 
Published: September 2023

BackgroundAUTO1 is a fast off-rate CD19-targeting chimeric antigen receptor (CAR), which has been successfully tested in adult lymphoblastic leukemia. Tscm/Tcm-enriched CAR-T populations confer the best expansion and persistence, but Tscm/Tcm numbers are poor in heavily pretreated adult patients. To improve this, we evaluate the use of AKT inhibitor (VIII) with the aim of uncoupling T-cell expansion from differentiation, to enrich Tscm/Tcm subsets.MethodsVIII was incorporated into the AUTO1 manufacturing process based on the semiautomated the CliniMACS Prodigy platform at both small and cGMP scale.ResultsAUTO1 manufactured with VIII showed Tscm/Tcm enrichment, improved expansion and cytotoxicity in vitro and superior antitumor activity in vivo. Further, VIII induced AUTO1 Th1/Th17 skewing, increased polyfunctionality, and conferred a unique metabolic profile and a novel signature for autophagy to support enhanced expansion and cytotoxicity. We show that VIII-cultured AUTO1 products from B-ALL patients on the ALLCAR19 study possess superior phenotype, metabolism, and function than parallel control products and that VIII-based manufacture is scalable to cGMP.ConclusionUltimately, AUTO1 generated with VIII may begin to overcome the product specific factors contributing to CD19+relapse.
Siglec-9+tumor-associated macrophages delineate an immunosuppressive subset with therapeutic vulnerability in patients with high-grade serous ovarian cancer
Authors: Wang Yiying , He Mengdi , Zhang Chen , Cao Kankan , Zhang Guodong , Yang Moran , Huang Yan , Jiang Wei , Liu Haiou 
Published: September 2023

BackgroundThe potent immunosuppressive properties of sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on myeloid cells and lymphocytes provide a strong rationale for serving as a therapeutic target. However, the expression profile and critical role of Siglec-9 in high-grade serous ovarian cancer (HGSC) remain obscure. This study aimed to elucidate the prognostic significance of Siglec-9 expression and its predictive value for immunotherapy in HGSC.MethodsStudy enrolled two cohorts, consisting of 120 tumor microarray specimens of HGSC for immunohistochemistry (IHC) and 40 fresh tumor specimens for flow cytometry (FCM). Expression profile of Siglec-9 in immune cells was analyzed by both bioinformatics analysis and FCM. Role of Siglec-9 was studied to identify that Siglec-9+TAMs linked with an immunosuppressive phenotype by IHC and FCM, and block Siglec-9 was sensitive to immunotherapy by ex vivo and in vitro assays.ResultsSiglec-9 is predominantly expressed on tumor-associated macrophages (TAMs). High Siglec-9+TAMs were associated with inferior overall survival (OS). Both tumor-conditioned medium (TCM) and tumor ascites induced enrichment of Siglec-9+TAMs with protumorigenic phenotypes. Siglec-9+TAMs were associated with immunosuppressive tumor microenvironment (TME) characterized by exhausted CD8+T cells and increased immune checkpoint expression. Blockade of Siglec-9 suppressed phosphorylation of the inhibitory phosphatase SHP-1 and repolarized TAMs to antitumorigenic phenotype and retrieved cytotoxic activity of CD8+T cells in vitro and ex vivo. Responders toward antiprogrammed death receptor-1 (anti-PD-1) therapy present more Siglec-9+TAMs than non-responders. Furthermore, blockade Siglec-9 synergized with anti-PD-1 antibody to enhance the cytotoxic activity of CD8+T cells in tissues with higher Siglec-9+TAMs.ConclusionsSiglec-9+TAMs may serve as an independent prognostic of poor survival but a predictive biomarker for anti-PD-1/antiprogrammed death ligand-1 immunotherapy in HGSC. In addition, the potential of immunosuppressive Siglec-9+TAMs as a therapeutic target is worth further exploration.