bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of workplace active rest programme on low back pain in office workers: a stepped-wedge cluster randomised controlled trial
Authors: Tsuboi Yamato , Oka Tomohiro , Nakatsuka Kiyomasa , Isa Tsunenori , Ono Rei 
Published: June 2021

ObjectiveThis study aimed to investigate the effectiveness of workplace active rest programme (WARP) on chronic low back pain (LBP) among office workers.DesignA closed cohort, stepped-wedge cluster randomised trial was conducted. The total duration of the study was 16 weeks (4 weeks for each step). Sequence allocation was randomised, but no one was blinded.SettingThis study was conducted in three offices in a Japanese electronics company. One office was for the administrative department, the others are for the engineering department.ParticipantsWe recruited 29 office workers with LBP greater than 3 months. LBP due to specific injury or disease was excluded. The median age was 38 years, and 26 (90%) were male. All participants completed the study.InterventionsIn the intervention phase, participants performed WARP comprising frequent stand-up and individualised brief exercise/physical activity during work. Physical therapists held an LBP workshop and developed tailor-made programmes before introducing WARP. We instructed participants to perform WARP at five timings during work. Control phase was set before the intervention and participants stayed as usual.Primary and secondary outcome measuresThe primary outcome was pain intensity of LBP assessed using the Brief Pain Inventory. The secondary outcomes were work productivity loss measured using the Work Limitations Questionnaire, LBP disability assessed using the Roland-Morris Disability Questionnaire, psychosocial subscale assessed using the STarT Back Screening Tool and physical activity measured using triaxial accelerometers. These outcomes were collected at baseline and at 4-month follow-up evaluation.ResultsIn the intention-to-treat analysis, WARP did not show any significant effects on pain intensity (β, 0.01; 95% CI −0.50 to 0.52) and on the secondary outcomes. The median adherence to WARP was 28.6% (IQR, 16.8–41.1), which was equal to 1.43 times per day. No adverse effect was observed.ConclusionsThe present study was unable to confirm the effectiveness of active rest in improving LBP. Hence, further study needs to investigate its effectiveness.Trial registration numberUMIN000033210.
How to increase the attractiveness of undergraduate rural clerkships? A cross-sectional study among medical students at two German medical schools
Authors: Herget Sabine , Nafziger Melanie , Sauer Stephanie , Bleckwenn Markus , Frese Thomas , Deutsch Tobias 
Published: June 2021

ObjectivesWhile literature provides substantial evidence that undergraduate rural clerkships may contribute to attract medical students to rural careers, so far little is known about how to convince medical students to choose rural teaching sites for their clerkships, which is usually optional. Thus, this study aimed to investigate students’ preferences and perceptions regarding different rural teaching and clerkship formats, important side conditions and suitable communication strategies to promote rural clerkships.DesignCross-sectional study based on a quantitative survey among medical students in advanced study years.SettingTwo German medical schools (Leipzig and Halle-Wittenberg).ParticipantsMedical students in third to fifth year (of six).ResultsResponse rate was 87.1% with n=909 analysable questionnaires. Participants’ mean age was 25.0 years and 65.2% were women. For 97.9% of the students completing some kind of rural clerkship was imaginable, for 90.8% even participation in a rural clerkship of 4 weeks and longer. Nearly half of the students (48.0%) specified that a rural clerkship 4 weeks and longer was ‘absolutely imaginable’. Younger age, having grown up in a rural or small-town region, being able to imagine future working in a small-town or rural area, and general practice as favoured, or at least conceivable career option were independently associated with a higher willingness to complete longer rural clerkships. Financial and organisational issues including remuneration of the clerkship, cost absorption for travelling and accommodation, and accessibility by public transport were the most important side conditions to increase the attractiveness of rural clerkships. Experience reports by fellow students, social media and informational events were stated to be the most suitable ways to advertise rural teaching offers.ConclusionsThe majority of the students are open-minded regarding even longer rural clerkships. This study adds new insights into measures that should be taken to convince them to actually chose this option.
Factors associated with incomplete immunisation in children aged 12–23 months at subnational level, Nigeria: a cross-sectional study
Authors: Eze Paul , Agu Ujunwa Justina , Aniebo Chioma Lynda , Agu Sergius Alex , Lawani Lucky Osaheni , Acharya Yubraj 
Published: June 2021

ObjectivesNational immunisation coverage rate masks subnational immunisation coverage gaps at the state and local district levels. The objective of the current study was to determine the sociodemographic factors associated with incomplete immunisation in children at a sub-national level.DesignCross-sectional study using the WHO sampling method (2018 Reference Manual).SettingFifty randomly selected clusters (wards) in four districts (two urban and two rural) in Enugu state, Nigeria.Participants1254 mothers of children aged 12–23 months in July 2020.Primary and secondary outcome measuresFully immunised children and not fully immunised children.ResultsFull immunisation coverage (FIC) rate in Enugu state was 78.9% (95% CI 76.5% to 81.1%). However, stark difference exists in FIC rate in urban versus rural districts. Only 55.5% of children in rural communities are fully immunised compared with 94.5% in urban communities. Significant factors associated with incomplete immunisation are: children of single mothers (aOR=5.74, 95% CI 1.45 to 22.76), children delivered without skilled birth attendant present (aOR=1.93, 95% CI 1.24 to 2.99), children of mothers who did not receive postnatal care (aOR=6.53, 95% CI 4.17 to 10.22), children of mothers with poor knowledge of routine immunisation (aOR=1.76, 95% CI 1.09 to 2.87), dwelling in rural district (aOR=7.49, 95% CI 4.84 to 11.59), low-income families (aOR=1.56, 95% CI 1.17 to 2.81) and living further than 30 min from the nearest vaccination facility (aOR=2.15, 95% CI 1.31 to 3.52).ConclusionsAlthough the proportion of fully immunised children in Enugu state is low, it is significantly lower in rural districts. Study findings suggest the need for innovative solutions to improve geographical accessibility and reinforce the importance of reporting vaccination coverage at local district level to identify districts for more targeted interventions.
Mortality trends and access to care for cardiovascular diseases in Agincourt, rural South Africa: a mixed-methods analysis of verbal autopsy data
Authors: Newberry Le Vay Jessica , Fraser Andrew , Byass Peter , Tollman Stephen , Kahn Kathleen , D’Ambruoso Lucia , Davies Justine I 
Published: June 2021

ObjectivesCardiovascular diseases are the second leading cause of mortality behind HIV/AIDS in South Africa. This study investigates cardiovascular disease mortality trends in rural South Africa over 20+ years and the associated barriers to accessing care, using verbal autopsy data.DesignA mixed-methods approach was used, combining descriptive analysis of mortality rates over time, by condition, sex and age group, quantitative analysis of circumstances of mortality (CoM) indicators and free text narratives of the final illness, and qualitative analysis of free texts.SettingThis study was done using verbal autopsy data from the Health and Socio-Demographic Surveillance System site in Agincourt, rural South Africa.ParticipantsDeaths attributable to cardiovascular diseases (acute cardiac disease, stroke, renal failure and other unspecified cardiac disease) from 1993 to 2015 were extracted from verbal autopsy data.ResultsBetween 1993 and 2015, of 15 305 registered deaths over 1 851 449 person-years of follow-up, 1434 (9.4%) were attributable to cardiovascular disease, corresponding to a crude mortality rate of 0.77 per 1000 person-years. Cardiovascular disease mortality rate increased from 0.34 to 1.12 between 1993 and 2015. Stroke was the dominant cause of death, responsible for 41.0% (588/1434) of all cardiovascular deaths across all years. Cardiovascular disease mortality rate was significantly higher in women and increased with age. The main delays in access to care during the final illness were in seeking and receiving care. Qualitative free-text analysis highlighted delays not captured in the CoM, principally communication between the clinician and patient or family. Half of cases initially sought care outside a hospital setting (50.9%, 199/391).ConclusionsThe temporal increase in deaths due to cardiovascular disease highlights the need for greater prevention and management strategies for these conditions, particularly for the women. Strategies to improve seeking and receiving care during the final illness are needed.
Effectiveness of combined vaginal progesterone and cervical cerclage in preventing preterm birth: a systematic review and meta-analysis protocol
Authors: Diacci Rosanna C , Issah Ashad , Williams Kimberley P , McAuliffe Liam , Aubin Anne-Marie , McAuliffe Jack E , Phung Jason , Wang Carol A , Pennell Craig E 
Published: June 2021

IntroductionPreterm birth (PTB) is the leading cause of death in children under 5 years. Preventive therapies targeted towards women with risk factors such as a prior PTB or a short cervix reduce the rate of PTB. Cervical cerclage, vaginal progesterone and a combination of the two have been used with no consensus as to whether combined treatment is more effective than any single treatment alone. The objective of this review is to determine the efficacy of combined treatment compared with cerclage alone and combined treatment compared with progesterone alone.Methods and analysisStudies will be sourced from the electronic databases Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Scopus, CINAHL (EBSCOhost) and Cochrane Library (Wiley) and reference lists. We will not exclude any papers due to publication date. Randomised control trials (RCTs), non-RCTs and cohort studies assessing single therapy (either progesterone or cerclage) versus combined therapy in women with a singleton pregnancy will be included. Two independent reviewers will conduct study screening (at abstract and full-text level), data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. Random or fixed effects models will be used depending on data heterogeneity and data will be presented as risk ratio for dichotomous data or mean difference for continuous data with a CI of 95% used for all outcomes.Ethics and disseminationNot applicable due to nature of the study type.PROSPERO registration numberCRD42020195975.
Country of birth, educational level and other predictors of seeking care due to decreased fetal movements: an observational study in Sweden using data from a cluster-randomised controlled trial
Authors: Radestad Ingela , Pettersson Karin , Lindgren Helena , Skokic Viktor , Akselsson Anna 
Published: June 2021

ObjectivesTo identify predictors of seeking care for decreased fetal movements and assess whether care-seeking behaviour is influenced by Mindfetalness.DesignObservational study with data from a cluster-randomised controlled trial.Setting67 maternity clinics and 6 obstetrical clinics in Sweden.ParticipantsAll pregnant women with a singleton pregnancy who contacted the obstetrical clinic due to decreased fetal movements from 32 weeks’ gestation of 39 865 women.MethodsData were collected from a cluster-randomised controlled trial where maternity clinics were randomised to Mindfetalness or routine care. Mindfetalness is a self-assessment method for women to use daily to become familiar with the unborn baby’s fetal movement pattern.Outcome measuresPredictors for contacting healthcare due to decreased fetal movements.ResultsOverall, 5.2% (n=2059) of women contacted healthcare due to decreased fetal movements, among which 1287 women (62.5%) were registered at a maternity clinic randomised to Mindfetalness and 772 women (37.5%) were randomised to routine care. Predictors for contacting healthcare due to decreased fetal movements were age, country of birth, educational level, parity, prolonged pregnancy and previous psychiatric care (p<0.001). The main differences were seen among women born in Africa as compared with Swedish-born women (2% vs 6%, relative risk (RR) 0.34, 95% CI 0.25 to 0.44) and among women with low educational level compared with women with university-level education (2% vs 5.4%, RR 0.36, 95% CI 0.19 to 0.62). Introducing Mindfetalness in maternity care increased the number of women seeking care due to decreased fetal movements overall.ConclusionWomen with country of birth outside Sweden and low educational level sought care for decreased fetal movements to a lesser extent compared with women born in Sweden and those with university degrees. Future research could explore whether pregnancy outcomes can be improved by motivating women in these groups to contact healthcare if they feel a decreased strength or frequency of fetal movements.Trial registration numberNCT02865759.
Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer
Authors: Zhai Tianhang , Wang Chao , Xu Yifeng , Huang Weifeng , Yuan Zhijun , Wang Tao , Dai Shuang , Peng Shaogang , Pang Tuling , Jiang Wenchao , Huang Yuhua , Zou Yuefeng , Xu Yingda , Sun Joanne , Gong Xinjiang , Zhang Jinping , Tsun Andy , Li Bin , Miao Xiaoniu 
Published: June 2021

BackgroundThe discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%–30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).MethodsTo determine the functional activity of the 4-1BB- and PD-L1-binding elements of PM1003, in vitro luciferase reporter and primary cell assays were used to test the potency of programmed cell death 1 ligand 1 (PD-L1) blockade and PD-L1-mediated 4-1BB activation via cross-bridging. X-ray crystallography was conducted to resolve the binding epitopes of the respective binding arms, and accurate binding kinetics were determined using standard affinity measurement techniques. Human 4-1BB and/or PD-L1 knock-in mice were used in cancer models for testing the in vivo antitumor efficacy of PM1003, and safety was evaluated further.ResultsPM1003 shows potent activation of 4-1BB and blockade of PD-L1 in cell-based assays. 4-1BB activation was exerted through the bridging of PD-L1 on target cells and 4-1BB on effector cells. No PD-L1-independent activation of 4-1BB was observed. Through X-ray crystallography, a unique binding epitope in the cysteine-rich domain 4 (CRD4) region was resolved that provides high potency and potentially low on-target toxicity as determined by primary immune cell assays and toxicity evaluation in vivo.ConclusionsA unique single-domain antibody was discovered that binds to the CRD4 domain of 4-1BB. When incorporated into a 4-1BB/PD-L1 bispecific (PM1003), we have shown the potent inhibition of PD-L1 activity with 4-1BB agonism upon cross-bridging with PD-L1 in vitro. Antitumor activity with minimal toxicity was found in vivo. Thus, PM1003 is a uniquely differentiating and next generation therapeutic agent for cancer therapy.
Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy
Authors: Reimann Hannah , Nguyen Andrew , Sanborn J Zachary , Vaske Charles J , Benz Stephen C , Niazi Kayvan , Rabizadeh Shahrooz , Spilman Patricia , Mackensen Andreas , Ruebner Matthias , Hein Alexander , Beckmann Matthias W , van der Meijden Edith D , Bausenwein Judith , Kretschmann Sascha , Griffioen Marieke , Schlom Jeffrey , Gulley James L , Lee Karin L , Hamilton Duane H , Soon-Shiong Patrick , Fasching Peter A , Kremer Anita N. 
Published: June 2021

BackgroundTherapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the antigenicity of expressed neoepitopes. Herein we describe a neoepitope and cognate neoepitope-reactive T-cell identification and validation program that supports the development of next-generation immunotherapies.MethodsUsing GPS Cancer, NantOmics research, and The Cancer Genome Atlas databases, we developed a novel bioinformatic-based approach which assesses mutational load, neoepitope expression, human leukocyte antigen (HLA)-binding prediction, and in vitro confirmation of T-cell recognition to preferentially identify targetable neoepitopes. This program was validated by application to a BC cell line and confirmed using tumor biopsies from two patients with BC enrolled in the Tumor-Infiltrating Lymphocytes and Genomics (TILGen) study.ResultsThe antigenicity and HLA-A2 restriction of the BC cell line predicted neoepitopes were determined by reactivity of T cells from HLA-A2-expressing healthy donors. For the TILGen subjects, tumor-infiltrating lymphocytes (TILs) recognized the predicted neoepitopes both as peptides and on retroviral expression in HLA-matched Epstein-Barr virus–lymphoblastoid cell line and BC cell line MCF-7 cells; PCR clonotyping revealed the presence of T cells in the periphery with T-cell receptors for the predicted neoepitopes. These high-avidity immune responses were polyclonal, mutation-specific and restricted to either HLA class I or II. Interestingly, we observed the persistence and expansion of polyclonal T-cell responses following neoadjuvant chemotherapy.ConclusionsWe demonstrate our neoepitope prediction program allows for the successful identification of neoepitopes targeted by TILs in patients with BC, providing a means to identify tumor-specific immunogenic targets for individualized treatment, including vaccines or adoptively transferred cellular therapies.
Incremental predictive value of left atrial strain and left atrial appendage function in rhythm outcome of non-valvular atrial fibrillation patients after catheter ablation
Authors: Ma Xin-Xin , Wang Aiqing , Lin Kaibin 
Published: June 2021

ObjectiveThe purpose of this study was to develop a non-invasive and convenient nomogram based on speckle tracking echocardiography, left atrial appendage function and clinical factors to predict the risk of atrial fibrillation (AF) recurrence after catheter ablation.MethodsA total of 124 prospectively consecutive patients with AF treated with catheter ablation in our hospital was retrospectively analysis. Baseline echocardiographic parameters were measured by using transthoracic and transesophageal echocardiography before ablation. Multivariate analysis was performed for selecting predictors for a nomogram and internal validation and calibration were evaluated by the bootstep method.ResultsDuring the follow-up of 12±3 months, 41 patients (33.1%) occurred AF recurrence after catheter ablation, while 83 patients (66.9%) had maintained sinus rhythm. Four predictors (AF type, left atrial appendage emptying flow velocity, left Atrial maximal volumes index and global longitudinal strain) with the P<0.5 was selected into the nomogram according to multivariate findings. Internal validation by bootstrapping with 1000 resamples was determined C-index of the nomogram for prediction AF recurrence was 0.901, which showed optimal discrimination and calibration of the established nomogram.ConclusionsNomogram based on echocardiography and clinical characteristics had good predictive performance for the possibility of AF recurrence, which providing practical guidance for individualised management of patients with AF after catheter ablation.
Interhospital and interindividual variability in secondary prevention: a comparison of outpatients with a history of chronic coronary syndrome versus outpatients with a history of acute coronary syndrome (the iASPIRE Study)
Authors: Curneen James MG , Judge Conor , Traynor Bryan , Buckley Anthony , Saiva Lavanya , Murphy Laura , Murray Donal , Fleming Sean , Kearney Peter , Murphy Ross T , Aleong Godfrey , Kiernan Thomas J , O'Neill James , Moore David , Nicaodhabhui Bridog , Birrane John , Hall Patricia , Crowley James , Gibson Irene , Jennings Catriona S , Wood David , Kotseva Kornelia , McEvoy John William 
Published: June 2021

BackgroundStudying variability in the care provided to secondary prevention coronary heart disease (CHD) outpatients can identify interventions to improve their outcomes.MethodsWe studied outpatients who had an index CHD event in the preceding 6–24 months. Eligible CHD events included acute coronary syndrome (ACS) and coronary revascularisation for stable chronic coronary syndrome (CCS). Site training was provided by a core team and data were collected using standardised methods.ResultsBetween 2017 and 2019, we enrolled 721 outpatients at nine Irish study sites; 81% were men and mean age was 63.9 (SD ±8.9) years. The study examination occurred a median of 1.16 years after the index CHD event, which was ACS in 399 participants (55%) and stable-CCS in 322. On examination, 42.5% had blood pressure (BP) >140/90 mm Hg, 63.7% had low-density lipoprotein cholesterol (LDL-C) >1.8 mmol/L and 44.1% of known diabetics had an HbA1c >7%. There was marked variability in risk factor control, both by study site and, in particular, by index presentation type. For example, 82% of outpatients with prior-ACS had attended cardiac rehabilitation versus 59% outpatients with prior-CCS (p<0.001) and there were also large differences in control of traditional risk factors like LDL-C (p=0.002) and systolic BP (p<0.001) among outpatients with prior-ACS versus prior-CCS as the index presentation.ConclusionsDespite international secondary prevention guidelines broadly recommending the same risk factor targets for all adults with CHD, we found marked differences in outpatient risk factor control and management on the basis of hospital location and index CHD presentation type (acute vs chronic). These findings highlight the need to reduce hospital-level and patient-level variability in preventive care to improve outcomes; a lesson that should inform CHD prevention programmes in Ireland and around the world.