bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lumbar Intervertebral Kinematics During an Unstable Sitting Task and Its Association With Standing-Induced Low Back Pain
Authors: Viggiani Daniel , Mannen Erin M. , Nelson-Wong Erika , Wong Alexander , Ghiselli Gary , Shelburne Kevin B. , Davidson Bradley S. , Callaghan Jack P. 
Published: September 2020

People developing transient low back pain during standing have altered control of their spine and hips during standing tasks, but the transfer of these responses to other tasks has not been assessed. This study used video fluoroscopy to assess lumbar spine intervertebral kinematics of people who do and do not develop standing-induced low back pain during a seated chair-tilting task. A total of 9 females and 8 males were categorized as pain developers (5 females and 3 males) or nonpain developers (4 females and 5 males) using a 2-hour standing exposure; pain developers reported transient low back pain and nonpain developers did not. Participants were imaged with sagittal plane fluoroscopy at 25 Hz while cyclically tilting their pelvises anteriorly and posteriorly on an unstable chair. Intervertebral angles, relative contributions, and anterior–posterior translations were measured for the L3/L4, L4/L5, and L5/S1 joints and compared between sexes, pain groups, joints, and tilting directions. Female pain developers experienced more extension in their L5/S1 joints in both tilting directions compared with female nonpain developers, a finding not present in males. The specificity in intervertebral kinematics to sex-pain group combinations suggests that these subgroups of pain developers and nonpain developers may implement different control strategies.
Pediatric emergency department utilisation during Ramadan: a retrospective cross-sectional study
Authors: Sawaya Rasha D , Wakil Cynthia , Shayya Sami , Al Hariri Moustafa , Dakessian Alik , Wazir Adonis , Makki Maha , Jamali Sarah , Tamim Hani 
Published: September 2020

ObjectiveTo investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED).DesignRetrospective cross-sectional study.SettingPED of a tertiary care centre in Lebanon.PatientsAll paediatric patients.ExposureRamadan (June 2016 and 2017) versus the months before and after Ramadan (non-Ramadan).Main outcome measuresPatient and illness characteristics and PED metrics including peak patient load; presentation timings; length of stay; and times to order tests, receive samples and report results.ResultsWe included 5711 patients with mean age of 6.1±5.3 years and 55.4% males. The number of daily visits was 28.3±6.5 during Ramadan versus 31.5±7.3 during non-Ramadan (p=0.004). The peak time of visits ranged from 18:00 to 22:00 during non-Ramadan versus from 22:00 to 02:00 during Ramadan. During Ramadan, there were significantly more gastrointestinal (GI) and trauma-related complaints (39.0% vs 35.4%, p=0.01 and 2.9% vs 1.8%, p=0.005). The Ramadan group had faster work efficiency measures such as times to order tests (21.1±21.3 vs 24.3±28.1 min, p<0.0001) and to collect samples (50.7±44.5 vs 54.8±42.6 min, p=0.03).ConclusionsRamadan changes presentation patterns, with fewer daily visits and a later peak time of visits. Ramadan also affects illness presentation patterns with more GI and trauma cases. Fasting times during Ramadan did not affect staff work efficiency. These findings could help EDs structure their staffing to optimise resource allocation during Ramadan.
Exploring the health and service utilisation of general practice patients with a history of adverse childhood experiences (ACEs): an observational study using electronic health records
Authors: Hardcastle Katie , Bellis Mark A , Sharp Catherine A , Hughes Karen 
Published: September 2020

ObjectivesTo examine the relationships between adverse childhood experiences (ACEs), chronic health and health service utilisation among a sample of general practice patients.DesignCross-sectional observational study using anonymised data from electronic health records for 763 patients.SettingFour general practices in northwest England and North Wales.Outcome measuresPatient demographic data (age, gender); body mass index; self-reported smoking status; self-reported ACEs; diagnosis of chronic health conditions; current mental health problems; total number of service contacts and repeat medication use in the previous 6 months.ResultsA history of ACEs (experiencing abuse or neglect as a child, and/or growing up in a household characterised by violence, substance use, mental health problems or criminal behaviour) was strongly independently associated with current mental health problems, smoking and chronic obstructive pulmonary disease, showing a dose–response relationship with level of ACE exposure. Medication use and contact were significantly greater among patients with high ACE exposure (≥4 ACEs), compared with those with no ACEs. However, contrary to findings from population studies, health service utilisation was not significantly different for patients with increased ACE exposure (1–3 ACEs) and their ACE-free counterparts.ConclusionsFindings highlight the contribution ACEs make to unequal distributions of risk to health and well-being and patterns of health service use in the UK.
Cadaveric simulation versus standard training for postgraduate trauma and orthopaedic surgical trainees: protocol for the CAD:TRAUMA study multicentre randomised controlled educational trial
Authors: James Hannah K , Pattison Giles T R , Fisher Joanne D , Griffin Damian 
Published: September 2020

IntroductionThe quantity and quality of surgical training in the UK has been negatively affected by reduced working hours and National Health Service (NHS) financial pressures. Traditionally surgical training has occurred by the master-apprentice model involving a process of graduated responsibility, but a modern alternative is to use simulation for the early stages of training. It is not known if simulation training for junior trainees can safeguard patients and improve clinical outcomes. This paper details the protocol for a multicentre randomised controlled educational trial of a cadaveric simulation training intervention versus standard training for junior postgraduate orthopaedic surgeons-in-training. This is the first study to assess the effect of cadaveric simulation training for open surgery on patient outcome. The feasibility of delivering cadaveric training, use of radiographic and clinical outcome measures to assess impact and the challenges of upscaling provision will be explored.Methods and analysisWe will recruit postgraduate orthopaedic surgeons-in-training in the first 3 years (of 8) of the specialist training programme. Participants will be block randomised and allocated to either cadaveric simulation or standard ‘on-the-job’ training, learning three common orthopaedic procedures, each of which is a substudy within the trial. The procedures are (1) dynamic hip screw, (2) hemiarthroplasty and (3) ankle fracture fixation. These procedures have been selected as they are very common procedures which are routinely performed by junior surgeons-in-training. A pragmatic approach to sample size is taken in lieu of a formal power calculation as this is novel exploratory work with no a priori estimate of effect size to reference. The primary outcome measure is the technical success of the surgery performed on patients by the participating surgeons-in-training during the follow-up period for the three substudy procedures, as measured by the implant position on the postoperative radiograph. The secondary outcome measures are procedure time, postoperative complication rate and patient health state at 4 months postoperation (EQ-5D—substudies 1 and 2 only).Ethics, registration and disseminationNational research ethics approval was granted for this study by the NHS Research Authority South Birmingham Research Ethics Committee (15/WM/0464). Confidentiality Advisory Group approval was granted for accessing radiographic and outcome data without patient consent on 27 February 2017 (16/CAG/0125). The results of this trial will be submitted to a peer-reviewed journal and will inform educational and clinical practice.Trial registration numberISRCTN20431944
Inequalities in complete childhood immunisation in Nepal: results from a population-based cross-sectional study
Authors: Song In Han , Palley Elizabeth , Atteraya Madhu Sudhan 
Published: September 2020

ObjectiveTo investigate the effect of different aspects of inequality on childhood immunisation rates in Nepal. The study hypothesised that social inequality factors (eg, gender of a child, age of mother, caste/ethnic affiliation, mother’s socioeconomic status, place of residence and other structural barrier factors such as living in extreme poverty and distance to health facility) affect the likelihood of children being immunised.DesignUsing gender of a child, age of mother, caste/ethnic affiliation, mother’s socioeconomic status, place of residence and other structural barrier factors such as living in extreme poverty and distance to health facility as independent variables, we performed bivariate and multivariate logistic regression analyses.SettingThis study used data from the most recent nationally representative cross-sectional Nepal Demographic and Health Survey in 2016.ParticipantsThe analysis reviewed data from 1025 children aged 12–23 months old.Outcome measuresThe main outcome variable was childhood immunisation.ResultsOnly 79.2% of children were fully immunised. The complete vaccination rate of ethnic/caste subpopulations ranged from 66.4% to 85.2%. Similarly, multivariate analysis revealed that children from the previously untouchable caste (OR 0.58; CI 0.33 to 0.99) and the Terai caste (OR 0.54; CI 0.29 to 0.99) were less likely to be fully immunised than children from the high Hindu caste.ConclusionGiven Nepal’s limited resources, we suggest that programmes that target the families of children who are least likely to be fully immunised, specifically those who are not only poor but also in financial crises and ‘underprivileged’ caste families, might be an effective strategy to improve Nepal’s childhood immunisation rates.
Cohort profile: the PHARMO Perinatal Research Network (PPRN) in the Netherlands: a population-based mother–child linked cohort
Authors: Houben E. , Broeders L. , Steegers E.A.P. , Herings R.M.C. 
Published: September 2020

PurposeObservational population-based research is a very suitable non-invasive method for studies in the vulnerable populations of pregnant women and children. Therefore, the PHARMO Perinatal Research Network (PPRN) was set up as a resource for life course perinatal and paediatric research by linking population-based data from existing registrations.ParticipantsFrom 1999 to 2017, the PPRN captures approximately 542 900 pregnancies of 387 100 mothers (‘Pregnancy Cohort’). Additionally, mother–child linkage is currently available for a quarter of these pregnancies (‘Child Cohort’). The PPRN contains preconceptional information on maternal healthcare, as well as detailed pregnancy and neonatal data, extending into long-term follow-up and outcomes after birth for both mother and child up to nearly 20 years. It includes linked data from different primary and secondary healthcare settings.Findings to dateThrough record linkage of the Netherlands Perinatal Registry and the PHARMO Database Network, we have established a large population-based research network including data on demographics, medication use, medical conditions and details concerning labour, birth and neonatal outcomes. Here, we provide an overview of record types available from the PPRN, available database follow-up and pregnancy characteristics of the PPRN cohorts. The PPRN has been used for a number of different pharmacoepidemiological studies, for example, to confirm that preterm-born infants were more likely than full-term infants to be hospitalised or use medication. Similar long-term comparisons showed that children born following spontaneous preterm labour were at increased risk of neurodevelopmental and respiratory conditions. Most recently, the PPRN provided important evidence on the trends in use of potentially harmful medication during pregnancy.Future plansThe PPRN provides a unique and rich data set facilitating large-scale observational pharmacoepidemiological perinatal research. The patient-level linkage of many different healthcare data sources allows for long-term follow-up of mother and child, with ongoing annual updates.
Clinical risk score to predict in-hospital mortality in COVID-19 patients: a retrospective cohort study
Authors: Fumagalli Carlo , Rozzini Renzo , Vannini Matteo , Coccia Flaminia , Cesaroni Giulia , Mazzeo Francesca , Cola Maria , Bartoloni Alessandro , Fontanari Paolo , Lavorini Federico , Marcucci Rossella , Morettini Alessandro , Nozzoli Carlo , Peris Adriano , Pieralli Filippo , Pini Riccardo , Poggesi Loredana , Ungar Andrea , Fumagalli Stefano , Marchionni Niccolò 
Published: September 2020

ObjectivesSeveral physiological abnormalities that develop during COVID-19 are associated with increased mortality. In the present study, we aimed to develop a clinical risk score to predict the in-hospital mortality in COVID-19 patients, based on a set of variables available soon after the hospitalisation triage.SettingRetrospective cohort study of 516 patients consecutively admitted for COVID-19 to two Italian tertiary hospitals located in Northern and Central Italy were collected from 22 February 2020 (date of first admission) to 10 April 2020.ParticipantsConsecutive patients≥18 years admitted for COVID-19.Main outcome measuresSimple clinical and laboratory findings readily available after triage were compared by patients’ survival status (‘dead’ vs ‘alive’), with the objective of identifying baseline variables associated with mortality. These were used to build a COVID-19 in-hospital mortality risk score (COVID-19MRS).ResultsMean age was 67±13 years (mean±SD), and 66.9% were male. Using Cox regression analysis, tertiles of increasing age (≥75, upper vs <62 years, lower: HR 7.92; p<0.001) and number of chronic diseases (≥4 vs 0–1: HR 2.09; p=0.007), respiratory rate (HR 1.04 per unit increase; p=0.001), PaO2/FiO2 (HR 0.995 per unit increase; p<0.001), serum creatinine (HR 1.34 per unit increase; p<0.001) and platelet count (HR 0.995 per unit increase; p=0.001) were predictors of mortality. All six predictors were used to build the COVID-19MRS (Area Under the Curve 0.90, 95% CI 0.87 to 0.93), which proved to be highly accurate in stratifying patients at low, intermediate and high risk of in-hospital death (p<0.001).ConclusionsThe COVID-19MRS is a rapid, operator-independent and inexpensive clinical tool that objectively predicts mortality in patients with COVID-19. The score could be helpful from triage to guide earlier assignment of COVID-19 patients to the most appropriate level of care.
EZH2-Targeted Therapies in Cancer: Hype or a Reality
Authors: Eich Marie-Lisa , Athar Mohammad , Ferguson James E. , Varambally Sooryanarayana 
Published: September 2020

Abstract
Next-generation genomic sequencing has identified multiple novel molecular alterations in cancer. Since the identification of DNA methylation and histone modification, it has become evident that genes encoding epigenetic modifiers that locally and globally regulate gene expression play a crucial role in normal development and cancer progression. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is the enzymatic catalytic subunit of the polycomb-repressive complex 2 (PRC2) that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). EZH2 is involved in global transcriptional repression, mainly targeting tumor-suppressor genes. EZH2 is commonly overexpressed in cancer and shows activating mutations in subtypes of lymphoma. Extensive studies have uncovered an important role for EZH2 in cancer progression and have suggested that it may be a useful therapeutic target. In addition, tumors harboring mutations in other epigenetic genes such as ARID1A, KDM6, and BAP1 are highly sensitive to EZH2 inhibition, thus increasing its potential as a therapeutic target. Recent studies also suggest that inhibition of EZH2 enhances the response to tumor immunotherapy. Many small-molecule inhibitors have been developed to target EZH2 or the PRC2 complex, with some of these inhibitors now in early clinical trials reporting clinical responses with acceptable tolerability. In this review, we highlight the recent advances in targeting EZH2, its successes, and potential limitations, and we discuss the future directions of this therapeutic subclass.
Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction
Authors: Ruiz-Villalba Adrián , Romero Juan P. , Hernández Silvia C. , Vilas-Zornoza Amaia , Fortelny Nikolaus , Castro-Labrador Laura , San Martin-Uriz Patxi , Lorenzo-Vivas Erika , García-Olloqui Paula , Palacio Marcel , Gavira Juan José , Bastarrika Gorka , Janssens Stefan , Wu Ming , Iglesias Elena , Abizanda Gloria , de Morentin Xabier Martinez , Lasaga Miren , Planell Nuria , Bock Christoph , Alignani Diego , Medal Gema , Prudovsky Igor , Jin Yong-Ri , Ryzhov Sergey , Yin Haifeng , Pelacho Beatriz , Gomez-Cabrero David , Lindner Volkhard , Lara-Astiaso David , Prósper Felipe 
Published: September 2020

Background:
Cardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heterogeneity in response to cardiac damage is lacking. The purpose of this study was to define CF heterogeneity during ventricular remodeling and the underlying mechanisms that regulate CF function.

Methods:
Collagen1α1–GFP (green fluorescent protein)–positive CFs were characterized after myocardial infarction (MI) by single-cell and bulk RNA sequencing, assay for transposase-accessible chromatin sequencing, and functional assays. Swine and patient samples were studied using bulk RNA sequencing.

Results:
We identified and characterized a unique CF subpopulation that emerges after MI in mice. These activated fibroblasts exhibit a clear profibrotic signature, express high levels of Cthrc1 (collagen triple helix repeat containing 1), and localize into the scar. Noncanonical transforming growth factor–β signaling and different transcription factors including SOX9 are important regulators mediating their response to cardiac injury. Absence of CTHRC1 results in pronounced lethality attributable to ventricular rupture. A population of CFs with a similar transcriptome was identified in a swine model of MI and in heart tissue from patients with MI and dilated cardiomyopathy.

Conclusions:

We report CF heterogeneity and their dynamics during the course of MI and redefine the CFs that respond to cardiac injury and participate in myocardial remodeling. Our study identifies
CTHRC1
as a novel regulator of the healing scar process and a target for future translational studies.
Eicosanoid Inflammatory Mediators Are Robustly Associated With Blood Pressure in the General Population
Authors: Palmu Joonatan , Watrous Jeramie D. , Mercader Kysha , Havulinna Aki S. , Lagerborg Kim A. , Salosensaari Aaro , Inouye Mike , Larson Martin G. , Rong Jian , Vasan Ramachandran S. , Lahti Leo , Andres Allen , Cheng Susan , Jousilahti Pekka , Salomaa Veikko , Jain Mohit , Niiranen Teemu J. 
Published: September 2020

Background
Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid–derived eicosanoids serve as mediators of inflammation and have been suggested to regulate renal vascular tone, peripheral resistance, renin‐angiotensin system, and endothelial function. We hypothesize that specific proinflammatory and anti‐inflammatory eicosanoids are linked with BP.

Methods and Results

We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women; mean age, 48±13 years) and, for external validation, a sample of 2859 FHS (Framingham Heart Study) Offspring study participants (55% women; mean age, 66±9 years). Using nontargeted liquid chromatography–mass spectrometry, we profiled 545 distinct high‐quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP (
P
<Bonferroni‐corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 (95% CI, 8.0–10.1) mm Hg higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS.

Conclusions
Plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights about the pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.
Dural Arteriovenous Fistulae After Cerebral Venous Thrombosis
Authors: Ferro José M. , Coutinho Jonathan M. , Jansen Olav , Bendszus Martin , Dentali Francesco , Kobayashi Adam , van der Veen Bas , Miede Corinna , Caria Jorge , Huisman Holger , Diener Hans-Christoph ,   on behalf of the RE-SPECT CVT Study Group
Published: September 2020

Background and Purpose:
This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging.

Methods:
RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial.

Results:
We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up.

Conclusions:
Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02913326.