bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detailed study protocol for systematic scoping review of research on child marriage, 2000–2019
Authors: Greene Margaret E. , Siddiqi Manahil 
Published: March 2021

IntroductionThe global development agenda reflects greater attention to ending child marriage and supporting adolescent girls than ever before. Limited understandings of the evidence base on child marriage, however, make it challenging to assess gaps in the literature and inform policy and programming to respond to the needs of adolescent girls. The goal of this project is to systematically identify, evaluate and synthesise the global evidence on child marriage.Methods and analysisWe will include articles with a thematic focus on child marriage from all geographic settings, two decades of research (2000–2019) and in four languages (English, Spanish, French and Portuguese). We will search 18 electronic academic databases (7 in English and 4 each in French, Spanish and Portuguese, with 1 overlapping database) and for the grey literature, conduct targeted hand-searches of organisations engaged in work to prevent child marriage. The databases for studies in English are PubMed, PsychINFO, Embase, CINAHL Plus, Popline, Web of Science and Cochrane Library; for studies in French, the databases will be DialNet, Directory of Open Access Journals, Science Direct and Biblioteca CCG-IBT database; in Spanish, DialNet, La Biblioteca Científica Electrónica en Línea, Red Iberoamericana de Innovación y Conocimiento Científico and Jstor and in Portuguese, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Biblioteca Virtual em Saúde, Biblioteca Científica Eletrônica On-line and Biblioteca Digital Brasileira de Teses e Dissertações. We will also review reference lists of select articles and seek input from key authors, field practitioners and participants in international convenings. We will collect and analyse data on publication characteristics, including type of document, institutional affiliation, publication year, language, focus country and region, study objective, specific focus, research method, key findings and recommendations of the material offered for future work. The database searches for publications in English were conducted in January 2020 and we plan to complete the searches in French, Spanish and Portuguese in early 2021.Ethics and disseminationAs a systematic review of already-published data, this study does not raise ethical or safety concerns. The authors plan to publish the results of the scoping review in a relevant international journal as well as present the results widely following publication. Building on this foundational work, the authors plan to conduct analyses that make use of the rich data.Registration detailsThe study design adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our protocol was registered with Open Science Framework on 14 January 2020 (https://osf.io/awh8v).
STEPFORWARD study: a randomised controlled feasibility trial of a self-aligning prosthetic ankle-foot for older patients with vascular-related amputations
Authors: Vanicek Natalie , Coleman Elizabeth , Watson Judith , Bell Kerry , McDaid Catriona , Barnett Cleveland , Twiste Martin , Jepson Fergus , Salawu Abayomi , Harrison Dennis , Mitchell Natasha 
Published: March 2021

ObjectivesTo determine the feasibility of conducting a full-scale randomised controlled trial (RCT) of the effectiveness and cost-effectiveness of a self-aligning prosthetic ankle-foot compared with a standard prosthetic ankle-foot.DesignMulticentre parallel group feasibility RCT.SettingFive prosthetics centres in England recruiting from July 2018 to August 2019.ParticipantsAdults aged ≥50 years with a vascular-related or non-traumatic transtibial amputation for 1 year or longer, categorised as having ‘limited community mobility’ and using a non-self-aligning ankle-foot.InterventionParticipants were randomised into one of two groups for 12 weeks: self-aligning prosthetic ankle-foot or existing non-self-aligning prosthetic ankle-foot.OutcomesFeasibility measures: recruitment, consent and retention rates; and completeness of questionnaire and clinical assessment datasets across multiple time points. Feasibility of collecting daily activity data with wearable technology and health resource use data with a bespoke questionnaire.ResultsFifty-five participants were randomised (61% of the target 90 participants): n=27 self-aligning ankle-foot group, n=28 non-self-aligning ankle-foot group. Fifty-one participants were included in the final analysis (71% of the target number of participants). The consent rate and retention at final follow-up were 86% and 93%, respectively. The average recruitment rate was 1.25 participants/site/month (95% CI 0.39 to 2.1). Completeness of questionnaires ranged from 89%–94%, and clinical assessments were 92%–95%, including the activity monitor data. The average completion rates for the EQ-5D-5L and bespoke resource use questionnaire were 93% and 63%, respectively.ConclusionsThis feasibility trial recruited and retained participants who were categorised as having ‘limited community mobility’ following a transtibial amputation. The high retention rate of 93% indicated the trial was acceptable to participants and feasible to deliver as a full-scale RCT. The findings support a future, fully powered evaluation of the effectiveness and cost-effectiveness of a self-aligning prosthetic ankle-foot compared with a standard non-self-aligning version with some adjustments to the trial design and delivery.Trial registration numberISRCTN15043643.
Danish teleophthalmology platform reduces optometry referrals into the national eye care system
Authors: Muttuvelu Danson Vasanthan , Buchholt Heidi , Nygaard Mads , Rasmussen Marie Louise Roed , Sim Dawn 
Published: March 2021

ObjectiveThe purpose of this study was to evaluate the stratification of follow-up and referral pathways after implementation of a systematic cloud-based electronic-referral teleophthalmological service for optometry-initiated ocular posterior segment disease referrals to the Danish national eye care system.Methods and AnalysisA retrospective cohort study was conducted in the period from 1 August 2018 to 31 July 2019. Patients with suspected ocular posterior segment disease reviewed by the telemedical ophthalmology service were included. The service stratified patients into the categories: no need for follow-up, follow-up by optometrist, follow-up by the telemedical service and referral to the national Danish eye care service.ResultsFrom a pool of 386 361 customers, 9938 patients were enrolled into this study. 19.5% of all patients were referred to the Danish national eye care system, while 80.5% of the patients in the telemedical service were not, in the period from 1 August 2018 to 31 July 2019. 14.4% of the optometrist referrals did not need any follow-up, while a majority of 66.1% needed some follow-up either by the optometrist themselves or within the telemedical service.ConclusionOptometrist posterior segment disease referrals can be considerably reduced with a risk stratified approach and optimal use of technology. New models can improve and streamline the healthcare system.
Associations between cardiac troponin I and cardiovascular parameters after 12-week endurance training in young moderately trained amateur athletes
Authors: Tesema Gashaw , George Mala 
Published: March 2021

BackgroundPrevious studies were conducted only on elite athletes, and they investigate acute training responses of cardiac troponin I (CTnI). However, cardiac troponin was found to be elevated in young and inexperienced athletes than adults, and immature myocardium is more susceptible to injury, which needs further consideration.AimTherefore, we aimed to observe the association between CTnI and cardiovascular parameters in response to chronic endurance training adaptation in young athletes.MethodsFifteen participants aged (19.5±1.3) years were selected and placed in endurance running at 70%–80% HRmax intensity for 35 min per training for the first week and additional 2 min each week from the second to the last week for 12 weeks. Serum cardiac troponin and cardiovascular parameters were assessed at pre-training and after 12 weeks of training.ResultWe find a significant CTnI level (p<0.05) and it is positively correlated with systolic blood pressure (BP) (r=0.425). Moreover, CTnI was statistically significant (p<0.01) and positively associated with mean arterial pressure (r=0.516) with a moderate correlation. Besides, CTnI showed a significant (p<0.001) and positive relationship with resting heart rate (r=0.605) and a moderate correlation. We did not find a significant relationship between CTnI and diastolic BP in response to endurance training adaptation.ConclusionIn conclusion, serum CTnI was significantly and positively associated with cardiovascular parameters in young amateur athletes in response to 12-week endurance training adaptation.
Palliative medicine referrals for hepatocellular carcinoma: a national survey of gastroenterologists
Authors: Sabih Abdul Hamid , Laube Robyn , Strasser Simone I , Lim Lynn , Cigolini Maria , Liu Ken 
Published: March 2021

ObjectivesPalliative care (PC) service involvement for hepatocellular carcinoma (HCC) patients is suboptimal and little is known about the underlying reasons for this. We aimed to study clinicians’ experience and attitudes towards PC in HCC.MethodsA nationwide survey was conducted of consultants/trainees recruited from the Gastroenterological Society of Australia membership directory. Clinician demographics, experience and attitudes towards PC use for HCC patients were collected.ResultsThere were 160 participants. Most attended weekly multidisciplinary team meetings (MDTM, 60%) and had no formal PC training (71%). MDTM with PC attendance was reported by 12%. Rates of PC referral increased incrementally from BCLC 0/A to D patients but were not universal even in advanced (46%) or terminal (87%) stages. Most acknowledged PC patient discussions occurred too late (61%). Those with prior PC training were more likely to refer BCLC 0/A and B patients for early PC. Referral rates for outpatient PC were higher in respondents who attended MDTM with PC present across all BCLC stages. PC service was rated good/very good by 70%/81% for outpatients/inpatients. Barriers to PC referral included clinician-perceived negative patient associations with PC (83%), clinician-perceived patient/caregiver lack of acceptance (81%/77%) and insufficient time (70%).ConclusionsPC referral for HCC patients is not universal and occurs late even in late-stage disease. Prior PC training and/or PC presence at MDTM positively influences referral practices. Barriers to PC referral are not related to quality of PC services but rather to clinician-perceived patients’ negative reactions to or lack of acceptance of PC.
Linked Colour imaging for the detection of polyps in patients with Lynch syndrome: a multicentre, parallel randomised controlled trial
Authors: Houwen Britt B S L , Hazewinkel Yark , Pellisé María , Rivero-Sánchez Liseth , Balaguer Francesc , Bisschops Raf , Tejpar Sabine , Repici Alessandro , Ramsoekh D , Jacobs Maarten A J M , Schreuder Ramon-Michel M , Kaminski Michal Filip , Rupinska Maria , Bhandari Pradeep , van Oijen Martijn G H , Koens Lianne , Bastiaansen Barbara A J , Tytgat Kristien M , Fockens Paul , Vleugels Jasper L A , Dekker E 
Published: March 2021

ObjectiveDespite regular colonoscopy surveillance, colorectal cancers still occur in patients with Lynch syndrome. Thus, detection of all relevant precancerous lesions remains very important. The present study investigates Linked Colour imaging (LCI), an image-enhancing technique, as compared with high-definition white light endoscopy (HD-WLE) for the detection of polyps in this patient group.DesignThis prospective, randomised controlled trial was performed by 22 experienced endoscopists from eight centres in six countries. Consecutive Lynch syndrome patients ≥18 years undergoing surveillance colonoscopy were randomised (1:1) and stratified by centre for inspection with either LCI or HD-WLE. Primary outcome was the polyp detection rate (PDR).ResultsBetween January 2018 and March 2020, 357 patients were randomised and 332 patients analysed (160 LCI, 172 HD-WLE; 6 excluded due to incomplete colonoscopies and 19 due to insufficient bowel cleanliness). No significant difference was observed in PDR with LCI (44.4%; 95% CI 36.5% to 52.4%) compared with HD-WLE (36.0%; 95% CI 28.9% to 43.7%) (p=0.12). Of the secondary outcome parameters, more adenomas were found on a patient (adenoma detection rate 36.3%; vs 25.6%; p=0.04) and a colonoscopy basis (mean adenomas per colonoscopy 0.65 vs 0.42; p=0.04). The median withdrawal time was not statistically different between LCI and HD-WLE (12 vs 11 min; p=0.16).ConclusionLCI did not improve the PDR compared with HD-WLE in patients with Lynch syndrome undergoing surveillance. The relevance of findings more adenomas by LCI has to be examined further.Trial registration numberNCT03344289.
Combination immunotherapy using G-CSF and oncolytic virotherapy reduces tumor growth in osteosarcoma
Authors: Morales-Molina Alvaro , Gambera Stefano , Leo Angela , García-Castro Javier 
Published: March 2021

BackgroundOsteosarcoma is the most common malignant solid tumor that affects bones, however, survival rates of patients with relapsed osteosarcoma have not improved in the last 30 years. Oncolytic virotherapy, which uses viruses designed to selectively replicate in cancer cells, has emerged as a promising treatment for solid tumors. Our group uses mesenchymal stem cells (MSCs) to transport oncolytic adenoviruses (OAds) to the tumor site, a therapeutic strategy called Celyvir. This treatment has been already applied in human patients, canine patients and different mouse models. In parallel, previous results have probed that administration of granulocyte-colony stimulating factor (G-CSF) increased immune infiltration in tumors. We then hypothesized that the mobilization of immune cells by G-CSF may increase the antitumor efficacy of Celyvir treatment by increasing the immune infiltration into the tumors.MethodsIn this study, we use a murine version of Celyvir consisting in murine MSCs carrying the murine OAd dlE102—here called OAd-MSCs—in an immunocompetent model of osteosarcoma. We tested the antitumoral efficacy of the combination of OAd-MSCs plus G-CSF.ResultsOur results show that treatment with OAd-MSCs or the union of OAd-MSCs with G-CSF (Combination) significantly reduced tumor growth of osteosarcoma in vivo. Moreover, treated tumors presented higher tumor infiltration of immune cells—especially tumor-infiltrating lymphocytes—and reduced T cell exhaustion, which seems to be enhanced in tumors treated with the Combination. The comparison of our results to those obtained from a cohort of pediatric osteosarcoma patients showed that the virotherapy induces immunological changes similar to those observed in patients with good prognosis.ConclusionsThe results open the possibility of using cellular virotherapy for the treatment of bone cancers. Indeed, its combination with G-CSF may be considered for the improvement of the therapy.
Fast progression in non–small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel
Authors: Gandara David , Reck Martin , Moro-Sibilot Denis , Mazieres Julien , Gadgeel Shirish , Morris Stefanie , Cardona Andres , Mendus Diana , Ballinger Marcus , Rittmeyer Achim , Peters Solange 
Published: March 2021

BackgroundTreatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study.MethodsThe OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non–small cell lung cancer. FP rates and associated baseline factors were analyzed. FP was defined as either a ≥50% increase in the sum of largest diameters (SLDs) within 6 weeks of treatment initiation or death due to cancer progression within 12 weeks (absent post-baseline scan).ResultsForty-two of 421 patients (10%) receiving atezolizumab and 37 of 402 (9%) receiving docetaxel had FP. Twenty patients with FP (48%) receiving atezolizumab versus 12 (30%) receiving docetaxel had a ≥50% SLD increase within 6 weeks. FP was significantly associated with an ECOG (Eastern Cooperative Oncology Group) performance status of 1 (vs 0), ≥3 metastatic sites at baseline, and failure of preceding first-line treatment within 6 months, but not with epidermal growth factor receptor mutation, programmed cell death 1 ligand 1 or tumor mutational burden. Overall survival in patients with FP and a ≥50% SLD increase at week 6 was similar with atezolizumab and docetaxel (unstratified HR 0.89 (95% CI 0.41 to 1.92)).ConclusionsFP rates were similar with atezolizumab and docetaxel in the OAK study, suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy. Applying the FP criteria to other phase III checkpoint inhibitor trials may further elucidate the risk factors for FP.Trial registration numberNCT02008227.
First immunotherapeutic CAR-T cells against the immune checkpoint protein HLA-G
Authors: Anna François , Bole-Richard Elodie , LeMaoult Joel , Escande Marie , Lecomte Martin , Certoux Jean-Marie , Souque Philippe , Garnache Francine , Adotevi Olivier , Langlade-Demoyen Pierre , Loustau Maria , Caumartin Julien 
Published: March 2021

BackgroundCAR-T cells immunotherapy is a breakthrough in the treatment of hematological malignancies such as acute lymphoblastic leukemia (ALL) and B-cell malignancies. However, CAR-T therapies face major hurdles such as the lack of tumor-specific antigen (TSA), and immunosuppressive tumor microenvironment sometimes caused by the tumorous expression of immune checkpoints (ICPs) such as HLA-G. Indeed, HLA-G is remarkable because it is both a potent ICP and a TSA. HLA-G tumor expression causes immune escape by impairing innate and adaptive immune responses and by inducing a suppressive microenvironment. Yet, to date, no immunotherapy targets it.MethodsWe have developed two anti-HLA-G third-generation CARs based on new anti-HLA-G monoclonal antibodies.ResultsAnti-HLA-G CAR-T cells were specific for immunosuppressive HLA-G isoforms. HLA-G-activated CAR-T cells polarized toward T helper 1, and became cytotoxic against HLA-G+tumor cells. In vivo, anti-HLA-G CAR-T cells were able to control and eliminate HLA-G+tumor cells. The interaction of tumor-HLA-G with interleukin (IL)T2-expressing T cells is known to result in effector T cell functional inhibition, but anti-HLA-G CAR-T cells were insensitive to this inhibition and still exerted their function even when expressing ILT2. Lastly, we show that anti-HLA-G CAR-T cells differentiated into long-term memory effector cells, and seemed not to lose function even after repeated stimulation by HLA-G-expressing tumor cells.ConclusionWe report for the first time that HLA-G, which is both a TSA and an ICP, constitutes a valid target for CAR-T cell therapy to specifically target and eliminate both tumor cells and HLA-G+suppressive cells.
Factors associated with time to independent walking recovery post-stroke
Authors: Kennedy Caitlin , Bernhardt Julie , Churilov Leonid , Collier Janice M , Ellery Fiona , Rethnam Venesha , Carvalho Lilian B , Donnan Geoffrey A , Hayward Kathryn S 
Published: March 2021

BackgroundPast studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT).MethodsThe outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics: age, sex, handedness; pre-stroke: hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation; stroke-related: stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention.ResultsA total of 2100 participants (median age 73 years, National Institutes of Health Stroke Scale 7, <1% missing data) with stroke were included. The median time to walking 50 m unassisted was 6 days (IQR 2–63) and 75% achieved independent walking by 3 months. Adjusted Cox regression indicated that slower return to independent walking was associated with older age (caHR 0.651, 95% CI 0.569 to 0.746), diabetes (caHR 0.836, 95% CI 0.740 to 0.945), severe stroke (caHR 0.094, 95% CI 0.072 to 0.122), haemorrhagic stroke (caHR 0.790, 95% CI 0.675 to 0.925) and right hemisphere stroke (caHR 0.796, 95% CI 0.714 to 0.887).ConclusionOur analysis provides robust evidence for important factors associated with independent walking recovery. These findings highlight the need for tailored mobilisation programmes that target subgroups, in particular people with haemorrhagic and severe stroke.
Hydroxychloroquine is associated with lower platelet activity and improved vascular health in systemic lupus erythematosus
Authors: Cornwell MacIntosh Grant , Luttrell-Williams Elliot S , Golpanian Michael , El Bannoudi Hanane , Myndzar Khrystyna , Izmirly Peter , Belmont H Michael , Katz Stuart , Smilowitz Nathaniel R , Engel Alexis , Clancy Robert , Ruggles Kelly , Buyon Jill P , Berger Jeffrey S 
Published: March 2021

ObjectiveHydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE.MethodsPlatelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose.ResultsAmong 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=−0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=−0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056).ConclusionHCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.