bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-centred infertility care: a scoping review protocol
Authors: Webair Hana Hasan , Ismail Tengku Alina Tengku , Ismail Shaiful Bahari , Mohd Noor Norhayati 
Published: November 2019

IntroductionPatient-centred infertility care (PCIC) is one of the quality indicators of effective fertility care. The application of this indicator requires a clear definition from the patient’s perspective. This proposed scoping review aims to explore the extent and nature of published scientific literature on PCIC in the past decade, identify gaps in the literature and define PCIC from infertile patients’ perspectives.Methods and analysisWe will conduct the proposed scoping review following the method of Arksey and O’Malley. The literature search will include studies published from 2009 to 2019, and will be conducted on the MEDLINE, PsycINFO, Scopus, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases; reference lists will be mined for literature not contained on these databases. A grey literature search will also be conducted. To be included in the review, studies should have been conducted on people with a history of infertility, with a focus on patient-centred fertility care. Studies that have not been published in full text and studies published in languages other than English will be excluded. After study selection, data will be charted in a prepared form. We will analyse the data using descriptive numerical and qualitative thematic analyses to answer the research questions. NVivo V.12 will be used for data extraction.Ethics and disseminationThis work does not warrant any ethical or safety concerns. This scoping review will synthesise existing literature on PCIC, and the results will be published to be readily available for clinical audiences and policymakers. These findings may support clinicians and decision-makers in applying PCIC, thereby promoting high-quality healthcare in the concerned population.
Global epidemiology of septic shock: a protocol for a systematic review and meta-analysis
Authors: Tianyi Frank Leonel , Tochie Joel Noutakdie , Danwang Celestin , Mbonda Aime , Temgoua Mazou N , Mapoh Sylvester Yari , Nkemngu Njinkeng J , Tallah Esther , Bigna Jean Joel 
Published: November 2019

BackgroundSeptic shock is a life-threatening infection frequently responsible for hospital admissions or may be acquired as nosocomial infection in hospitalized patients with resultant significant morbidity and mortality . There is a dearth of data on a résumé and meta-analysis on the global epidemiology of this potentially deadly condition. Therefore, we propose the first systematic review to synthesize existing data on the global incidence, prevalence and case fatality rate of septic shock worldwide.MethodsWe will include cross-sectional, case-control and cohort studies reporting on the incidence, and case fatality rate of septic shock. Electronic databases including PubMed, Embase, WHO Global Health Library and Web of Science will be searched for relevant records published between 1 January 2000 and 31 August 2019. Independents reviewers will perform study selection and data extraction, as well as assessment of methodological quality of included studies. Appropriate meta-analysis will then be used to pool studies judged to be clinically homogenous. Egger’s test and funnel plots will be used to detect publication bias. Findings will be reported and compared by human development level of countries.Ethics and disseminationBeing a review, ethical approval is not required as it was obtained in the primary study which will make up the review. This review is expected to provide relevant data to help in evaluating the burden of septic shock in the general population. The overall findings of this research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019129783.
Can Waterlow score predict 30-day mortality and length of stay in acutely admitted medical patients (aged ≥65 years)? Evidence from a single centre prospective cohort study
Authors: Wang James Wei , Smith Phillip , Sarker Shah-Jalal , Elands Sophie , Oliveira Amelia , Barratt Claire , Thorn Chris , Holme Tom , Lynch Mary 
Published: November 2019

ObjectiveThis study aimed to explore the potential for the Waterlow score (WS) to be used as a predictor of 30-day mortality and length of hospital stay (LHS) in acutely admitted medical patients aged 65 years and older.DesignProspective observational cohort study.SettingUK District General Hospital.Subjects834 consecutive patients aged 65 years and older admitted acutely to medical specialties between 30 May and 22 July 2014.MethodsAdmission WS (range 4–64) assessment paired with the patient’s status at 30 days in terms of mortality and their LHS.Primary outcomes30-day mortality and length of inpatient stay.Results834 consecutive acute medical admissions had their WS recorded. 30-day mortality was 13.1% (109 deaths). A significant difference in the distribution of WS (p<0.001) was seen between those who survived (median 12) and those who died (median 16) within 30 days, particularly within respiratory (p<0.001), stroke (p<0.001), cardiology (p<0.016), non-respiratory infections (p<0.018) and trauma (p<0.044) subgroups. Odds of dying within 30 days increased threefold for every 10-unit increase in the WS (p<0.001, 95% CI 2.1 to 4.3). LHS was also positively linearly associated with the WS in those who survived 30 days (median=5, IQR=10; r=0.32, p<0.01). A five-unit increase in WS was associated with approximately 5 days increase in LHS. On the other hand, quadratic regression showed this relationship was curvilinear and negative (concave) for those who died within 30 days where a five-unit increase in WS was associated with an approximately 10 days decrease in LHS.ConclusionThis study demonstrates an association between a high WS and both 30-day mortality and LHS. This is particularly significant for mortality in patients in the respiratory, stroke and cardiac subcategories. The WS, a nursing-led screening tool that is carried out on virtually all admissions to UK hospitals, could have additional use at the time of patient admission as a risk assessment tool for 30-day mortality as well as a predictor of LHS.
Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China
Authors: Chen Chao Yi , Xu Wei , Dai Yajun , Xu Weilan , Liu Chaojie , Wu Qunhong , Gao Lijun , Kang Zheng , Hao Yanhua , Ning Ning 
Published: November 2019

ObjectiveThis study aimed to assess household preparedness for emergency events and its determinants in China.DesignA cross-sectional questionnaire survey was conducted on 3541 households in China in 2015.ParticipantsHouseholds were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews.Outcome measuresHousehold emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values.ResultsOnly 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286).ConclusionHousehold preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.
The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis
Authors: Middleton Bianca Fleur , Jones Mark A , Waddington Claire S , Danchin Margaret , McCallum Carly , Gallagher Sarah , Leach Amanda Jane , Andrews Ross , Kirkwood Carl , Cunliffe Nigel , Carapetis Jonathan , Marsh Julie A , Snelling Tom 
Published: November 2019

IntroductionRotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis.Methods and analysisThis Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to <12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre <20 U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre >20 U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size.Ethics, registration and disseminationEthics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated.Trial registration numberNCT02941107; Pre-results.
Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort
Authors: Chen Ruoqing , Zhan Yiqiang , Pedersen Nancy , Fall Katja , Valdimarsdóttir Unnur A , Hägg Sara , Fang Fang 
Published: November 2019

ObjectiveTo investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association.DesignPopulation-based prospective cohort studySettingsSwedish Twin Registry.ParticipantsBased on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique.Main outcome measuresIncident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index.ResultsA total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:−0.014, 95% CI: −0.035, 0.007), widowed (β:−0.035, 95% CI: −0.061, –0.010), or living alone (β:−0.033, 95% CI: −0.052, –0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34).ConclusionsLiving singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.
Study protocol: a randomised non-inferiority trial using interactive virtual presence to remotely assist parents with child restraint installations
Authors: Schwebel David C , MacKay Jennifer Morag , Redden David 
Published: November 2019

BackgroundMotor vehicle crashes are the third-leading cause of death to American children aged 1–5 years. When installed correctly, child restraints (car seats) reduce risk of serious injury and death. However, most restraints are installed incorrectly. The current gold standard for correct installation is systematic car seat checks, where certified technicians help parents, but car seat checks are highly underused due to barriers in access, scheduling and resources.MethodsThe present study protocol describes plans to evaluate use of interactive virtual presence technology (interactive merged reality)—joint, simultaneous remote verbal and visual interaction and exposure to the same 3D stimuli—to assist remotely located parents installing child restraints. If effective, this technology could supplement or replace in-person checks and revolutionise how government, industry and non-profits help parents install child restraints properly. Building from preliminary studies, we propose a randomised non-inferiority trial to evaluate whether parents who install child restraints while communicating with remote expert technicians via interactive virtual presence on their smartphones achieve installations and learning not inferior in safety to parents who install restraints with on-site technicians. We will randomly assign 1476 caregivers at 7 US sites to install child restraints either via interactive virtual presence or live technicians. Correctness of installation will be assessed using objective checklists, both following installation and again 4 months later.ConclusionWe aim to demonstrate that child restraint installation is accurate (>90% correct) when conducted remotely, that such installations are not inferior to installation accuracy with live experts and that parents learn and retain information about child restraint installation.
Ultrasonographic measurement of adrenal gland‐to‐aorta ratio as a method of estimating adrenal size in dogs
Authors: Agut Amalia , Martinez Miryam , Anson Agustina , Soler Marta 
Published: November 2019

BackgroundAdrenal size has been used as the principal criterion for differentiating a normal gland from adrenal hyperplasia. The objectives of this study were to establish an ultrasonographic measurement of adrenal gland‐to‐aorta (adrenal/Ao) ratio to estimate the adrenal size and to assess the effects of bodyweight, age and sex on the adrenal/Ao ratio in non‐adrenal gland disease dogs.MethodsTwo hundred and thirty‐four dogs (120 entire females and 114 entire males) considered non‐adrenal gland disease were included in this study. Dogs were allocated into three bodyweight categories (<10 kg, 10–20 kg and >20 kg), and four age groups (<1 year, 1–5 years, 5–10 years and >10 years old). Measurements of the maximal thickness of caudal pole of both adrenal glands and the aortic luminal diameter in sagittal plane were performed on the ultrasonographic images. Three different ratios were calculated for each dog.ResultsSex and age did not influence on the adrenal/Ao ratio. There were differences (P<0.05) between the three dog sizes for adrenal/Ao ratio, being the highest value for small size and the lowest value for large size.ConclusionsIn this study, only bodyweight influences the ultrasound measurement of the adrenal/Ao ratio in non‐adrenal gland disease dogs.
Cosmological singularities in conformal Weyl gravity
Authors: Heydarzade Yaghoub 
Published: November 2019

AbstractIn this work, we study the issue of the past and future cosmological singularities in the context of the fourth-order conformal Weyl gravity. In particular, we investigate the emergent universe scenario proposed by Ellis et al., and find the stability conditions of the corresponding Einstein static state using the fixed point approach. We show that depending on the values of the parameters of the conformal Weyl gravity theory, there are possibilities for having initially stable emergent states for an FRW universe with both the positive and negative spatial curvatures. This represents that the conformal Weyl gravity can be free of the initial singularity problem. Then, following Barrow et al., we address the possible types of the finite-time future cosmological singularities. We discuss how these singularities also can be avoided in the context of this theory.
Prophylactic In Vivo Hematopoietic Stem Cell Gene Therapy with an Immune Checkpoint Inhibitor Reverses Tumor Growth in Syngeneic Mouse Tumor Models
Authors: Li Chang , Course Meredith M. , McNeish Iain A. , Drescher Charles W. , Valdmanis Paul N. , Lieber André 
Published: November 2019

Abstract

Population-wide testing for cancer-associated mutations has established that more than one-fifth of ovarian and breast carcinomas are associated with inherited risk. Salpingo-oophorectomy and/or mastectomy are currently the only effective options offered to women with high-risk germline mutations. Our goal here is to develop a long-lasting approach that provides immunoprophylaxis for mutation carriers. Our approach leverages the fact that at early stages, tumors recruit hematopoietic stem/progenitor cells (HSPC) from the bone marrow and differentiate them into tumor-supporting cells. We developed a technically simple technology to genetically modify HSPCs in vivo. The technology involves HSPC mobilization and intravenous injection of an integrating HDAd5/35++ vector. In vivo HSPC transduction with a GFP-expressing vector and subsequent implantation of syngeneic tumor cells showed &gt;80% GFP marking in tumor-infiltrating leukocytes. To control expression of transgenes, we developed a miRNA regulation system that is activated only when HSPCs are recruited to and differentiated by the tumor. We tested our approach using the immune checkpoint inhibitor anti-PD-L1-γ1 as an effector gene. In in vivo HSPC-transduced mice with implanted mouse mammary carcinoma (MMC) tumors, after initial tumor growth, tumors regressed and did not recur. Conventional treatment with an anti-PD-L1 mAb had no significant antitumor effect, indicating that early, self-activating expression of anti-PD-L1-γ1 can overcome the immunosuppressive environment in MMC tumors. The efficacy and safety of this approach was further validated in an ovarian cancer model with typical germline mutations (ID8 p53−/− brca2−/−), both in a prophylactic and therapeutic setting. This HSPC gene therapy approach has potential for clinical translation.

Significance:
Considering the limited prophylactic options that are currently offered to women with high-risk germ-line mutations, the in vivo HSPC gene therapy approach is a promising strategy that addresses a major medical problem.
HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor, in Patients with Clear Cell Renal Cell Carcinoma
Authors: Courtney Kevin D. , Ma Yuanqing , Diaz de Leon Alberto , Christie Alana , Xie Zhiqun , Woolford Layton , Singla Nirmish , Joyce Allison , Hill Haley , Madhuranthakam Ananth J. , Yuan Qing , Xi Yin , Zhang Yue , Chang Jenny , Fatunde Oluwatomilade , Arriaga Yull , Frankel Arthur E. , Kalva Sanjeeva , Zhang Song , McKenzie Tiffani , Reig Torras Oscar , Figlin Robert A. , Rini Brian I. , McKay Renée M. , Kapur Payal , Wang Tao , Pedrosa Ivan , Brugarolas James 
Published: November 2019

AbstractPurpose:The heterodimeric transcription factor HIF-2 is arguably the most important driver of clear cell renal cell carcinoma (ccRCC). Although considered undruggable, structural analyses at the University of Texas Southwestern Medical Center (UTSW, Dallas, TX) identified a vulnerability in the α subunit, which heterodimerizes with HIF1β, ultimately leading to the development of PT2385, a first-in-class inhibitor. PT2385 was safe and active in a first-in-human phase I clinical trial of patients with extensively pretreated ccRCC at UTSW and elsewhere. There were no dose-limiting toxicities, and disease control ≥4 months was achieved in 42% of patients.Patients and Methods:We conducted a prospective companion substudy involving a subset of patients enrolled in the phase I clinical trial at UTSW (n = 10), who were treated at the phase II dose or above, involving multiparametric MRI, blood draws, and serial biopsies for biochemical, whole exome, and RNA-sequencing studies.Results:PT2385 inhibited HIF-2 in nontumor tissues, as determined by a reduction in erythropoietin levels (a pharmacodynamic marker), in all but one patient, who had the lowest drug concentrations. PT2385 dissociated HIF-2 complexes in ccRCC metastases, and inhibited HIF-2 target gene expression. In contrast, HIF-1 complexes were unaffected. Prolonged PT2385 treatment resulted in the acquisition of resistance, and we identified a gatekeeper mutation (G323E) in HIF2α, which interferes with drug binding and precluded HIF-2 complex dissociation. In addition, we identified an acquired TP53 mutation elsewhere, suggesting a possible alternate mechanism of resistance.Conclusions:These findings demonstrate a core dependency on HIF-2 in metastatic ccRCC and establish PT2385 as a highly specific HIF-2 inhibitor in humans. New approaches will be required to target mutant HIF-2 beyond PT2385 or the closely related PT2977 (MK-6482).