bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of osteoporosis among North Korean women refugees living in South Korea: a comparative cross-sectional study
Authors: Kim Kyeong Jin , An Jee Hyun , Kim Kyoung Jin , Yu Ji Hee , Kim Nam Hoon , Yoo Hye Jin , Kim Hee Young , Seo Ji A , Kim Nan Hee , Choi Kyung Mook , Baik Sei Hyun , Kim Sin Gon 
Published: June 2020

ObjectiveTo investigate the prevalence of osteoporosis among North Korean women refugees when compared with South Korean women, who have identical genetic backgrounds but experience different environments.DesignComparative cross-sectional study.SettingNorth Korean Refugee Health in South Korea (NORNS) study in South Korea.ParticipantsWe evaluated 122 North Korean women who participated in NORNS study and 366 age-matched/menopausal status-matched South Korean women from the Korea University Medical Center (KUMC) health examination cohort. The median age of the NORNS participants was 46 years (IQR, 40–60 years) with 52 women (42.6%) being postmenopausal.ResultsAmong the postmenopausal women, NORNS participants had a higher body mass index and number of pregnancies and lower physical activity than the KUMC participants. The overall prevalence of osteoporosis was 48% (25/52) and 17% (27/156) in NORNS and KUMC participants, respectively. The bone mineral density (BMD) values at the lumbar spine, femur neck and total hip were significantly lower in postmenopausal NORNS women than in the postmenopausal KUMC women. Old age, low body weight and late age of menarche were associated with low BMD among the postmenopausal North Korean refugees. In premenopausal participants, the NORNS women had lower body weight and physical activity than the KUMC women at baseline. All the NORNS women had normal Z-scores, although the BMD at the lumbar spine was significantly lower in NORNS women than in the KUMC women (0.952 vs 1.002 g/cm2, p<0.001).ConclusionsOsteoporosis is a prevalent health problem in postmenopausal North Korean women refugees living in South Korea. It is conceivable to prepare vigilant countermeasures for bone health deterioration in this growing population, especially for postmenopausal women. Further research is warranted to determine the cause of the differences between participants of the same ethnic group.
Study protocol for an exploratory interventional study investigating the feasibility of video-based non-contact physiological monitoring in healthy volunteers by Mapping Of Lower Limb skIn pErfusion (MOLLIE)
Authors: Harford Mirae , Areia Carlos , Villarroel Mauricio , Jorge Joao , Finnegan Eoin , Davidson Shaun , Mahdi Adam , Young Duncan , Tarassenko Lionel , Watkinson Peter J 
Published: June 2020

IntroductionSkin perfusion varies in response to changes in the circulatory status. Blood flow to skin is reduced during haemodynamic collapse secondary to peripheral vasoconstriction, whereas increased skin perfusion is frequently observed when haemodynamics improve with resuscitation. These changes in perfusion may be monitored using non-contact image-based methods. Previous camera-derived physiological measurements have focused on accurate vital signs monitoring and extraction of physiological signals from environmental noise. One of the biggest challenges of camera-derived monitoring is artefacts from motion, which limits our understanding of what parameters may be derived from skin. In this study, we use phenylephrine and glyceryl trinitrate (GTN) to cause vasoconstriction and vasodilation in stationary healthy volunteers to describe directional changes in skin perfusion pattern.Methods and analysisWe aim to recruit 30 healthy volunteers who will undergo protocolised infusions of phenylephrine and GTN, followed by the monitored and timed release of a thigh tourniquet. The experimental timeline will be identical for all participants. Measurements of traditionally used haemodynamic markers (heart rate, blood pressure and stroke volume) and camera-derived measurements will be taken concurrently throughout the experimental period. The parameters of interest from the image data are skin colour and pattern, skin surface temperature, pulsatile signal detected at the skin surface and skin perfusion index.Ethics and disseminationThis study was reviewed and approved by the Oxford University Research and Ethics Committee and Clinical Trials and Research Governance teams (R63796/RE001). The results of this study will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberISRCTN10417167.
Improving gender equity in critical care medicine: a protocol to establish priorities and strategies for implementation
Authors: Parsons Leigh Jeanna , de Grood Chloe , Ahmed Sofia , Bosma Karen , Burns Karen E A , Fowler Robert , Fox-Robichaud Alison , Mehta Sangeeta , Mele Tina , Straus Sharon E , Zepeda Nubia , Kemp Laryssa , Fiest Kirsten , Stelfox Henry Thomas 
Published: June 2020

IntroductionWhile the number of women entering medical school now equals or surpasses the number of men, gender equity in medicine has not been achieved. Women continue to be under-represented in leadership roles (eg, deans, medical chairs) and senior faculty positions. In addition, women do not enter medical specialties as often as men, which can have important implications for work environment, reimbursement and the delivery of patient care. Compared with other medical specialties (eg, anaesthesiology, dermatology, etc), critical care medicine is a medical specialty with some of the lowest representation of women. While strategies to improve gender equity in critical care medicine exist in the published literature, efforts to comprehensively synthesise, prioritise and implement solutions have been limited.The objective of this programme of work is to establish priorities for the development and implementation of key strategies to improve the outcomes, well-being and experiences of women in critical care in Canada.Methods and analysisThree phases encompass this programme of work. In phase I, we will catalogue published strategies focused on improving gender inequity across medical specialties through a scoping review. In phase II, we will conduct a modified Delphi consensus process with decision-makers, physicians and researchers to identify key strategies (identified in phase I and proposed by participants in phase II) for improving gender inequity in the specialty of critical care medicine. Finally, in phase III, we will conduct a 1-day stakeholder meeting that engages participants from phase II to build capacity for the development and implementation of top ranked strategies. Data analyses from this programme of work will be both quantitative and qualitative.Ethics and disseminationThe proposed programme of work is a foundational step towards establishing targeted strategies to improve gender inequity in the medical specialty of critical care medicine. Strategies will be prioritised by stakeholders, mapped to preidentified drivers of gender equity in the specialty and be scalable to institutional needs. A final report of our results including the list of top prioritised strategies and implementation objectives will be disseminated to panel participants, critical care leadership teams and major critical care societies who are partners in this work, around the country to facilitate uptake at the local level.The University of Calgary Conjoint Health Research Ethics Board has approved this study (REB16-0890).
Variation in the estimated costs of pivotal clinical benefit trials supporting the US approval of new therapeutic agents, 2015–2017: a cross-sectional study
Authors: Moore Thomas J , Heyward James , Anderson Gerard , Alexander G Caleb 
Published: June 2020

ObjectivesLittle is routinely disclosed about the costs of the pivotal clinical trials that provide the key scientific evidence of the treatment benefits of new therapeutic agents. We expand our earlier research to examine why the estimated costs may vary 100-fold.DesignA cross-sectional study of the estimated costs of the pivotal clinical trials supporting the approval of 101 new therapeutic agents approved by the US Food and Drug Administration from 2015 to 2017.MethodsWe licensed a software tool used by the pharmaceutical industry to estimate the likely costs of clinical trials to be conducted by contract research organisations. For each trial we collected 52 study characteristics. Linear regression was used to assess the most important factors affecting costs.Primary and secondary outcome measuresThe mean and 95% CI of 225 pivotal clinical trials using varying assumptions. We also assessed median estimated costs per patient, per clinic visit and per drug.ResultsMeasured as pivotal trials cost per approved drug, the 101 new molecular entities had an estimated median cost of US$48 million (IQR US$20 million–US$102 million). The 225 individual clinical trials had a median estimate of US$19 million (IQR US$12 million–US$33 million) per trial and US$41 413 (IQR, US$29 894–US$75 047) per patient. The largest single factor driving cost was the number of patients required to establish the treatment effects and varied from 4 patients to 8442. Next was the number of trial clinic visits, which ranged from 2 to 166. Our statistical model showed trial costs rose exponentially with these two variables (R2=0.696, F=257.9, p<0.01).ConclusionsThe estimated costs are modest for measuring the benefits of new therapeutic agents but rise exponentially as more patients and clinic visits are required to establish a drug effect.
Development and evaluation of a novel protective device for upper gastrointestinal endoscopy in the COVID-19 pandemic: the EBOX
Authors: Mcleod Robert William John , Warren Neil , Roberts Stuart Ashley 
Published: June 2020

BackgroundDuring the COVID-19 pandemic, aerosol-generating procedures such as upper gastrointestinal endoscopy (UGIE) have been considered high risk. We designed a novel acrylic box (endoscopy box (EBOX)) with the intention of limiting aerosol and droplet spread during such procedures. We evaluated clinical utility, impact on the endoscopy team and also assessed the impact of the EBOX on macroscopic droplet spread from a simulated cough during UGIE.MethodsClinical utility was evaluated prospectively via EBOX use on 15 patients undergoing endoscopic retrograde cholangiopancreatography (13) or endoscopic ultrasound (2). Feedback was recorded from the endoscopy team regarding ease of positioning, impact of the EBOX on procedural performance and cleaning. A cough was simulated via explosion of a hyperinflated balloon containing 0.75 mL of ultraviolet disclosing lotion within the oral cavity of a mannequin, with and without the EBOX. Macroscopic spread was then evaluated with a ultraviolet torch.ResultsThree endoscopists and the team members found that the EBOX did not hamper the procedure and felt it was a useful adjunct to full personal protective equipment (PPE). Simulated cough without the EBOX identified macroscopic spread up to 2.3 m away from the patient’s mouth as well as onto key areas such as the exposed neck of the endoscopist, which is not considered in current PPE guidance. Simulated cough using the EBOX significantly reduced macroscopic spread onto key areas of the healthcare workers.ConclusionsThe EBOX is a valuable adjunct to recommended PPE for UGIE, but still allows these procedures to be performed in the standard manner.
Non-amplification genetic alterations ofHER2gene in non-small cell lung carcinoma
Authors: Mehta Anurag , Nathany Shrinidhi , Tripathi Rupal , Sharma Sanjeev Kumar , Saifi Mumtaz , Batra Ullas 
Published: June 2020

AimsThe present study investigated the incidence and spectrum of human epidermal growth factor receptor 2 (HER2) mutations, associated clinicopathological characteristics and the co-occurrence ofHER2gene amplification in theHER2gene mutated cases in non-small cell lung cancer (NSCLC).MethodsAll patients with advanced lung adenocarcinoma (LUAD) who underwent broad genomic profiling by next generation sequencing (NGS) from 2015 to 2019 were included in the study.HER2gene amplification was checked in all theHER2gene mutated cases. Tumour tissues of all the mutated cases were examined by fluorescent in situ hybridisation (FISH).ResultsFifty-four (37.2%) out of the 145 cases harboured tier 1 driver mutations comprisingEGFRin 22.1%, ALK rearrangements in 7.6% cases,ROS1rearrangements andBRAFV600Ein 3.5% cases each, andNTRKfusion in 0.7% cases. Nine (6.2%) cases exhibited a significant genetic alteration inHER2gene (tiers 2 and 3) on NGS. The most common alteration was exon 20 insertion of amino acid sequence AYVM in five cases (p.E770_A771insAYVM) followed by insertion of YVMA (p.A771_Y772insYVMA) in one case, insGSP (p.V777_G778insGSP) in one case and two missense mutations: p.G776C and p.QA795C (novel variant). The median copy number of the HER2 gene was 3.21 while on FISH, the median HER2/CEP17 ratio was 2.0.ConclusionsThere is a relatively higher occurrence ofHER2exon 20 mutations as primary oncogenic driver in NSCLC especially LUAD. Our cohort has demonstrated (p.E770_A771insAYVM) as the strikingly dominant insertion mutation against the most often globally reported (p.A771_Y772insYVMA).
Association between air pollution and lung development in schoolchildren in China
Authors: Wang Tao , Wang Haitao , Chen Jian , Wang Jiansheng , Ren Dunqiang , Hu Wei , Wang Hongmei , Han Wei , Leng Shuguang , Zhang Rong , Zheng Yuxin 
Published: June 2020

BackgroundChina has been facing nationwide air pollution at unprecedented high levels primarily from fossil–fuel combustion in the past decade. However, few studies have been conducted on the adverse effect of severe air pollution on lung development in school-age children.MethodsUsing wellness check and air pollution data from 2014 to 2017, we conducted a retrospective analysis of lung development in 21 616 school-age children from Shijiazhuang and Qingdao from North China with severe vs mild air pollution. Linear mixed effects model was performed to assess the effect of air pollution on forced vital capacity (FVC) growth.ResultsExposure to severe air pollution was associated with a dramatic reduction in annual FVC growth rate (−71.3 mL, p< 0.001). In addition, every 10 μg/m3increase in annual PM2.5level was associated with a reduction of annual FVC growth by 12.2 mL ( p< 0.001). Sex discrepancy (boys vs girls) in FVC growth was greater in Qingdao (35.4 mL/year, 95% CI: 26.0 to 44.7) than in Shijiazhuang (19.8 mL/year, 95% CI: 9.3 to 30.3) (p for interaction=0.063). Exposure to indoor coal- or wood-burning stove heating (−79.4 mL, p< 0.001) and secondhand smoke at home (−59.3 mL, p= 0.003) were inversely associated with FVC growth.ConclusionOur study raised serious alarm over the threat of severe air pollution to lung development in school-age children. Sex discrepancy in lung development was reduced dramatically in heavily polluted area.
HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression
Authors: Chen Alan Chen , Xu Renhuan , Wang Tao , Wei Junping , Yang Xiao-Yi , Liu Cong-Xiao , Lei Gangjun , Lyerly Herbert Kim , Heiland Teri , Hartman Zachary Conrad 
Published: June 2020

BackgroundThe advent of immune checkpoint blockade antibodies has demonstrated that effective mobilization of T cell responses can cause tumor regression of metastatic cancers, although these responses are heterogeneous and restricted to certain histologic types of cancer. To enhance these responses, there has been renewed emphasis in developing effective cancer-specific vaccines to stimulate and direct T cell immunity to important oncologic targets, such as the oncogene human epidermal growth factor receptor 2 (HER2), expressed in ~20% of breast cancers (BCs).MethodsIn our study, we explored the use of alternative antigen trafficking through use of a lysosome-associated membrane protein 1 (LAMP) domain to enhance vaccine efficacy against HER2 and other model antigens in bothin vitroandin vivostudies.ResultsWe found that inclusion of this domain in plasmid vaccines effectively trafficked antigens to endolysosomal compartments, resulting in enhanced major histocompatibility complex (MHC) class I and II presentation. Additionally, this augmented the expansion/activation of antigen-specific CD4+ and CD8+ T cells and also led to elevated levels of antigen-specific polyfunctional CD8+ T cells. Significantly, vaccination with HER2-LAMP produced tumor regression in ~30% of vaccinated mice with established tumors in an endogenous model of metastatic HER2+ BC, compared with 0% of HER2-WT vaccinated mice. This therapeutic benefit is associated with enhanced tumor infiltration of activated CD4+ and CD8+ T cells.ConclusionsThese data demonstrate the potential of using LAMP-based endolysosomal trafficking as a means to augment the generation of polyfunctional, antigen-specific T cells in order to improve antitumor therapeutic responses using cancer antigen vaccines.
Absence of SCAPER causes male infertility in humans andDrosophilaby modulating microtubule dynamics during meiosis
Authors: Wormser Ohad , Levy Ygal , Bakhrat Anna , Bonaccorsi Silvia , Graziadio Lucia , Gatti Maurizio , AbuMadighem Ali , McKenney Richard J , Okada Kyoko , El Riati Saad , Har-Vardi Iris , Huleihel Mahmoud , Levitas Eliahu , Birk Ohad S , Abdu Uri 
Published: June 2020

BackgroundMutationin S-phase cyclin A-associated protein rin the endoplasmic reticulum(SCAPER) have been found across ethnicities and have been shown to cause variable penetrance of an array of pathological traits, including intellectual disability, retinitis pigmentosa and ciliopathies.MethodsHuman clinical phenotyping, surgical testicular sperm extraction and testicular tissue staining. Generation and analysis ofshort spindle 3(ssp3) (SCAPERorthologue)DrosophilaCAS9-knockout lines. In vitro microtubule (MT) binding assayed by total internal reflection fluorescence microscopy.ResultsWe show that patients homozygous for aSCAPERmutation lack SCAPER expression in spermatogonia (SPG) and are azoospermic due to early defects in spermatogenesis, leading to the complete absence of meiotic cells.Interestingly,Drosophila null mutants for the ubiquitously expressedssp3gene are viable and female fertile but male sterile. We further show that male sterility inssp3null mutants is due to failure in both chromosome segregation and cytokinesis. In cells undergoing male meiosis, the MTs emanating from the centrosomes do not appear to interact properly with the chromosomes, which remain dispersed within dividing spermatocytes (SPCs). In addition, mutant SPCs are unable to assemble a normal central spindle and undergo cytokinesis. Consistent with these results, an in vitro assay demonstrated that both SCAPER and Ssp3 directly bind MTs.ConclusionsOur results show thatSCAPERnull mutations block the entry into meiosis of SPG, causing azoospermia. Null mutations inssp3specifically disrupt MT dynamics during male meiosis, leading to sterility. Moreover, both SCAPER and Ssp3 bind MTs in vitro. These results raise the intriguing possibility of a common feature between human andDrosophilameiosis.
Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non‐blinded, prospective clinical trial
Authors: Molina Jenifer , Jean‐Philippe Clementine , Conboy Lisa , Añor Sonia , de la Fuente Cristian , Wrzosek Marcin Adam , Spycher Andrea , Luchsinger Eva , Wenger‐Riggenbach Bettina , Montoliu Patricia , Gandini Gualtiero , Menchetti Marika , Ribeiro João Carlos , Varejão Artur , Ferreira Antonio , Zanghi Brian , Volk Holger Andreas 
Published: June 2020

BackgroundDespite appropriate antiseizure drug (ASD) treatment, around two‐thirds of dogs with idiopathic epilepsy (IE) have seizures long‐term and 20–30per cent of affected dogs remain poorly controlled.MethodsThe current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study.ResultsThe mean seizure frequency per month, averaged over the entire 84‐day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P<0.001) by 42per cent. QoL was reported as very good to excellent (>8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial.ConclusionsThis study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies.
Advancing animal welfare and ethics in veterinary practice through a national pet wellbeing task force, practice‐based champions and clinical audit
Authors: Wensley Sean , Betton Vicki , Martin Nicola , Tipton Emma 
Published: June 2020

BackgroundVeterinary animal welfare advocacy can be undertaken at individual, community, national and international levels. The People's Dispensary for Sick Animals (PDSA), a veterinary charity with 48 Pet Hospitals UK‐wide, created a consultative staff network to put an explicit organisational focus on animal welfare–focused veterinary practice.MethodsPDSA created a national internal committee—a Pet Wellbeing Task Force—composed of veterinary staff representatives. Together with recruited hospital‐based Champions who serve as a focus for animal welfare and ethics within their clinical teams, the resulting staff network has described a vision of animal welfare and ethics within companion animal veterinary practice, with accompanying practice‐level actions. These actions have formed the basis for national clinical audit, repeated three times since 2013.ResultsThe audit, alongside targeted interventions, has driven organisational change (eg, new policies), led to measurable improvements in pet wellbeing (eg, improved pain assessment and management) and stimulated collaborative practice‐based research with universities.ConclusionA dedicated staff network has facilitated organisation‐wide communication on animal welfare and ethics; offered a safe space to raise and discuss animal welfare and ethical issues; and fostered leadership, by working towards model veterinary practice with respect to animal welfare and ethics, with benefits for pet patients, staff and the wider veterinary and veterinary nursing professions.