bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations and practices for holistic chronic obstructive pulmonary disease (COPD) assessment and optimal referral patterns in emergency department presentations: a scoping review protocol
Authors: Moloney Clint , Sneath Emily , Phillips Tania , Issac Hancy , Beccaria Gavin , Mullens Amy 
Published: August 2019

IntroductionChronic obstructive pulmonary disease (COPD) is a common respiratory condition that causes persistent respiratory symptoms and decline in lung function over many years. This chronic disease significantly affects health-related quality of life and is known to contribute to frequent emergency department (ED) presentations. Multidimensional management of these patients, including interconnecting health disciplinarians will allow holistic care provision in the ED. The purpose of this scoping review is to synthesise current evidence on holistic management and assessment, and referral practices stemming from acute COPD presentation in the ED. Specifically, to determine: (1) What are the known causal factors associated with COPD ED presentations and (2) Is there an identified connection with appropriate healthcare professional assessment within ED presentations and reported referral pathways?Methods and analysisThe iterative stages of the Arskey and O’Malley, and Levac advanced scoping review framework informs this review. Using published and unpublished studies in English, a three-tiered search strategy will be applied. After duplicates are removed, screen 1 (title and abstract) and screen 2 (full-text) will be conducted by two independent reviewers to determine eligibility of articles. Disputes will be settled through discussion or by using a third reviewer. A data collection tool developed by the authors will inform the data extraction process. Schematic tabular format of results with a narrative summary will depict how the results link with the scoping review objectives. Categorisation of results will be narrowed down as key conceptual findings and will align with the strategic intent of this review.Ethics and disseminationEthics approval was not required for this study. A multidisciplinary team of authors will participate in dissemination activities (publications, reports, conference presentations, framework development).
Validation of new ICD-10-based patient safety indicators for identification of in-hospital complications in surgical patients: a study of diagnostic accuracy
Authors: McIsaac Daniel I , Hamilton Gavin M , Abdulla Karim , Lavallée Luke T , Moloo Husien , Pysyk Chris , Tufts Jocelyn , Ghali William A , Forster Alan J 
Published: August 2019

ObjectiveAdministrative data systems are used to identify hospital-based patient safety events; few studies evaluate their accuracy. We assessed the accuracy of a new set of patient safety indicators (PSIs; designed to identify in hospital complications).Study designProspectively defined analysis of registry data (1 April 2010–29 February 2016) in a Canadian hospital network. Assignment of complications was by two methods independently. The National Surgical Quality Improvement Programme (NSQIP) database was the clinical reference standard (primary outcome=any in-hospital NSQIP complication); PSI clusters were assigned using International Classification of Disease (ICD-10) codes in the discharge abstract. Our primary analysis assessed the accuracy of any PSI condition compared with any complication in the NSQIP; secondary analysis evaluated accuracy of complication-specific PSIs.PatientsAll inpatient surgical cases captured in NSQIP data.AnalysisWe assessed the accuracy of PSIs (with NSQIP as reference standard) using positive and negative predictive values (PPV/NPV), as well as positive and negative likelihood ratios (±LR).ResultsWe identified 12 898 linked episodes of care. Complications were identified by PSIs and NSQIP in 2415 (18.7%) and 2885 (22.4%) episodes, respectively. The presence of any PSI code had a PPV of 0.55 (95% CI 0.53 to 0.57) and NPV of 0.93 (95% CI 0.92 to 0.93); +LR 6.41 (95% CI 6.01 to 6.84) and −LR 0.40 (95% CI 0.37 to 0.42). Subgroup analyses (by surgery type and urgency) showed similar performance. Complication-specific PSIs had high NPVs (95% CI 0.92 to 0.99), but low to moderate PPVs (0.13–0.61).ConclusionValidation of the ICD-10 PSI system suggests applicability as a first screening step, integrated with data from other sources, to produce an adverse event detection pathway that informs learning healthcare systems. However, accuracy was insufficient to directly identify or rule out individual-level complications.
No rest for the weary: a cross-sectional study comparing patients’ sleep in the emergency department to those on the ward
Authors: Prendiville Richard , Umana Etimbuk , Avalos Gloria , McNicholl Brian 
Published: August 2019

BackgroundBoarding in emergency departments (EDs) is a persistent problem worldwide. We hypothesised that patients sleeping while being boarded in EDs have worse self-rated sleep than those admitted from EDs who sleep on the ward.MethodsProspective cross-sectional study conducted at the University College Hospital, Galway between October and November 2016. Self-rated sleep in patients boarded in EDs from 23:00 to 07:00 was compared with those admitted to the ward before 23:00. Patients rated their sleep using the Richards-Campbell Sleep Questionnaire. Patients were excluded if they had cognitive impairment, were unable or incapacitated or had evidence of alcohol or drug use in the previous 24 hours. Continuous data are shown as medians (IQRs 25th–75th percentiles). Linear regression models of log-transformed outcome variables were performed.ResultsNinety-three patients were included and 22 were excluded. Patients who boarded in the ED were significantly more likely to be medical patients (78% vs 21%, p<0.001), to be older (median age (IQR)=60 (39-71) vs 47 (32-68), p=0.04) and have more urgent presentations (74% vs 48% presenting as Manchester triage category 1 or 2, p=0.01) than patients who sleep on a ward. Patients who slept on the ward had significantly better sleep scores (mean log-transformed sleep scores (SD)=2.92 (1.05) vs 3.72 (0.66), p<0.001)). Those sleeping in the ED reported greater noisiness than those sleeping on the ward (mean log-transformed noisiness scores (SD)=3.18 (1.10) vs 4.15 (0.57), p<0.001). These significant differences in sleep scores and noisiness ratings persisted after adjustment for age, triage category and admitting service.ConclusionWe found those who sleep boarded in EDs have worse self-rated sleep than those who sleep on the ward.
De novo SCAMP5 mutation causes a neurodevelopmental disorder with autistic features and seizures
Authors: Hubert Laurence , Cannata Serio Magda , Villoing-Gaudé Laure , Boddaert Nathalie , Kaminska Anna , Rio Marlène , Lyonnet Stanislas , Munnich Arnold , Poirier Karine , Simons Matias , Besmond Claude 
Published: August 2019

BackgroundAutistic spectrum disorders (ASDs) with developmental delay and seizures are a genetically heterogeneous group of diseases caused by at least 700 different genes. Still, a number of cases remain genetically undiagnosed.ObjectiveThe objective of this study was to identify and characterise pathogenic variants in two individuals from unrelated families, both of whom presented a similar clinical phenotype that included an ASD, intellectual disability (ID) and seizures.MethodsWhole-exome sequencing was used to identify pathogenic variants in the two individuals. Functional studies performed in the Drosophila melanogaster model was used to assess the protein function in vivo.ResultsProbands shared a heterozygous de novo secretory carrier membrane protein (SCAMP5) variant (NM_001178111.1:c.538G>T) resulting in a p.Gly180Trp missense variant. SCAMP5 belongs to a family of tetraspanin membrane proteins found in secretory and endocytic compartments of neuronal synapses. In the fly SCAMP orthologue, the p.Gly302Trp genotype corresponds to human p.Gly180Trp. Western blot analysis of proteins overexpressed in the Drosophila fat body showed strongly reduced levels of the SCAMP p.Gly302Trp protein compared with the wild-type protein, indicating that the mutant either reduced expression or increased turnover of the protein. The expression of the fly homologue of the human SCAMP5 p.Gly180Trp mutation caused similar eye and neuronal phenotypes as the expression of SCAMP RNAi, suggesting a dominant-negative effect.ConclusionOur study identifies SCAMP5 deficiency as a cause for ASD and ID and underscores the importance of synaptic vesicular trafficking in neurodevelopmental disorders.
Association of novel measures of sleep disturbances with blood pressure: the Multi-Ethnic Study of Atherosclerosis
Authors: Kim John S. , Azarbarzin Ali , Wang Rui , Djonlagic Ina E. , Punjabi Naresh M. , Zee Phyllis C. , Koo Brian B. , Soliman Elsayed Z. , Younes Magdy , Redline Susan 
Published: August 2019

BackgroundMechanisms underlying blood pressure (BP) changes in obstructive sleep apnoea (OSA) are incompletely understood. We assessed the associations between BP and selected polysomnography (PSG) traits: sleep depth, airflow limitation measurements and OSA-specific hypoxic burden.MethodsThis cross-sectional analysis included 2055 participants from the Multi-Ethnic Study of Atherosclerosis who underwent PSG and BP measurements in 2010–2013. Sleep depth was assessed using the ‘OR product’, a continuous measure of arousability. Airflow limitation was assessed by duty cycle (Ti/Tt) and % of breaths with flow limitation, and hypoxia by ‘hypoxic burden’. Primary outcomes were medication-adjusted systolic BP (SBP) and diastolic BP (DBP). We used generalised linear models adjusted for age, sex, race/ethnicity, smoking, education, body mass index, alcohol use, periodic limb movements and alternative physiological disturbances.ResultsThe sample had a mean age of 68.4 years and apnoea–hypopnoea index of 14.8 events/hour. Sleep depth was not significantly associated with BP. Every 1 SD increment in log-transformed non-rapid eye movement duty cycle was associated with 0.9% decrease in SBP (95% CI: 0.1% to 1.6%), even after adjusting for sleep depth and hypoxic burden. Every 1 SD increment in log-transformed hypoxic burden was associated with a 1.1% increase in SBP (95% CI: 0.1% to 2.1%) and 1.9% increase in DBP (95% CI: 1.0% to 2.8%) among those not using hypertension medications.ConclusionsHigher duty cycle was associated with lower SBP overall and hypoxic burden with higher SBP and DBP among non-BP medication users. These findings suggest changes in both respiratory effort and oxygenation during sleep influence BP.
PARP Inhibition Suppresses GR–MYCN–CDK5–RB1–E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer
Authors: Liu Bo , Li Likun , Yang Guang , Geng Chuandong , Luo Yong , Wu Wenhui , Manyam Ganiraju C. , Korentzelos Dimitrios , Park Sanghee , Tang Zhe , Wu Cheng , Dong Zhenyang , Sigouros Michael , Sboner Andrea , Beltran Himisha , Chen Yu , Corn Paul G. , Tetzlaff Michael T. , Troncoso Patricia , Broom Bradley , Thompson Timothy C. 
Published: August 2019

Abstract

Purpose:
In this study, we addressed the underlying mechanisms for the association between enzalutamide (ENZ) treatment and neuroendocrine prostate cancer (NEPC), and the critical involvement of MYCN, and loss of RB1 function in neuroendocrine differentiation (NED) of prostatic epithelial cells, and the development of NEPC. We further sought to determine whether PARP inhibition could suppress NEPC, and to identify molecular determinants of this therapeutic activity.

Experimental Design:
We used a novel prostate cancer patient–derived xenograft (PDX) treatment model, prostatic adenocarcinoma and NEPC cell lines, an NEPC organoid line, and NEPC xenograft models to address the mechanistic basis of ENZ-induced NED, and to analyze suppression of NED and NEPC growth by PARP inhibition.

Results:
We identified an ENZ treatment–associated glucocorticoid receptor (GR)–MYCN–CDK5–RB1–E2F1 signaling pathway that drives NED in prostatic adenocarcinoma PDX and cell line models. Mechanistically, long-term ENZ treatment transcriptionally upregulates signaling of the GR–MYCN axis, leading to CDK5R1 and CDK5R2 upregulation, Rb1 phosphorylation, and N-Myc–mediated and E2F1-mediated NED gene expression. Importantly, olaparib (OLA) or talazoparib (TALA) suppressed these activities, and the combination of OLA and dinaciclib (DINA), an inhibitor of CDK2 and CDK5, which also inhibits Rb1 phosphorylation, suppressed NED and significantly improved therapeutic efficiency in NEPC cells in vitro and in NEPC tumors in vivo.

Conclusions:
The results of our study indicate an important role of GR–MYCN–CDK5R1/2–RB1–NED signaling in ENZ-induced and PARP inhibitor–suppressed NEPC. We also demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models.
Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Authors: Hao Huai-Xiang , Wang Hongyun , Liu Chen , Kovats Steven , Velazquez Roberto , Lu Hengyu , Pant Bhavesh , Shirley Matthew , Meyer Matthew J. , Pu Minying , Lim Joanne , Fleming Michael , Alexander LeighAnn , Farsidjani Ali , LaMarche Matthew J. , Moody Susan , Silver Serena J. , Caponigro Giordano , Stuart Darrin D. , Abrams Tinya J. , Hammerman Peter S. , Williams Juliet , Engelman Jeffrey A. , Goldoni Silvia , Mohseni Morvarid 
Published: August 2019

Abstract
KRAS, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective inhibition of the protein tyrosine phosphatase, SHP2, can impair the proliferation of KRAS-mutant cancer cells in vitro and in vivo using cell line xenografts and primary human tumors. In vitro, sensitivity of KRAS-mutant cells toward the allosteric SHP2 inhibitor, SHP099, is not apparent when cells are grown on plastic in 2D monolayer, but is revealed when cells are grown as 3D multicellular spheroids. This antitumor activity is also observed in vivo in mouse models. Interrogation of the MAPK pathway in SHP099-treated KRAS-mutant cancer models demonstrated similar modulation of p-ERK and DUSP6 transcripts in 2D, 3D, and in vivo, suggesting a MAPK pathway–dependent mechanism and possible non-MAPK pathway–dependent mechanisms in tumor cells or tumor microenvironment for the in vivo efficacy. For the KRASG12C MIAPaCa-2 model, we demonstrate that the efficacy is cancer cell intrinsic as there is minimal antiangiogenic activity by SHP099, and the effects of SHP099 is recapitulated by genetic depletion of SHP2 in cancer cells. Furthermore, we demonstrate that SHP099 efficacy in KRAS-mutant models can be recapitulated with RTK inhibitors, suggesting RTK activity is responsible for the SHP2 activation. Taken together, these data reveal that many KRAS-mutant cancers depend on upstream signaling from RTK and SHP2, and provide a new therapeutic framework for treating KRAS-mutant cancers with SHP2 inhibitors.
Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75)
Authors: Ouchi Yasuyoshi , Sasaki Jun , Arai Hidenori , Yokote Koutaro , Harada Kazumasa , Katayama Yasuo , Urabe Takao , Uchida Yasufumi , Hayashi Masaru , Yokota Naoto , Nishida Hirokazu , Otonari Takatoshi , Arai Tadashi , Sakuma Ichiro , Sakabe Kazuo , Yamamoto Masayasu , Kobayashi Takashi , Oikawa Shinichi , Yamashita Shizuya , Rakugi Hiromi , Imai Takumi , Tanaka Shiro , Ohashi Yasuo , Kuwabara Masanari , Ito Hideki 
Published: August 2019

Background:
Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C–lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients.

Methods:
This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke.

Results:

Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50–0.86;
P
=0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37–0.98;
P
=0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18–0.79;
P
=0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups.

Conclusions:
LDL-C–lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution.

Clinical Registration:

URL:
https://www.umin.ac.jp
. Unique identifier: UMIN000001988.
How Are Emergent Constraints Quantifying Uncertainty and What Do They Leave Behind?
Authors: Williamson Daniel B. , Sansom Philip G. 
Published: August 2019

AbstractThe use of emergent constraints to quantify uncertainty for policy-relevant quantities such as equilibrium climate sensitivity (ECS) has become increasingly widespread in recent years. Many researchers, however, claim that emergent constraints are inappropriate or even underreport uncertainty. In this paper we contribute to this discussion by examining the emergent constraints methodology in terms of its underpinning statistical assumptions. We argue that the statistical assumptions required to underpin existing frameworks are strong, hard to defend, and lead to an underreporting of uncertainty. We show how weakening them leads to a more transparent Bayesian framework wherein hitherto-ignored sources of uncertainty, such as how reality might differ from models, can be quantified. We present a guided framework for the quantification of additional uncertainties that is linked to the confidence we can have in the underpinning physical arguments for using linear constraints. We provide a software tool for implementing our framework for emergent constraints and use it to illustrate the methods on a number of recent emergent constraints for ECS. We find that the robustness of any constraint to additional uncertainties depends strongly on the confidence we have in the underpinning physics, allowing a future framing of the debate over the validity of a particular constraint around underlying physical arguments, rather than statistical assumptions. We also find that when physical arguments lead to confidence in the linear relationships underpinning emergent constraints, prediction intervals are only slightly widened by including additional uncertainties, and they show this across a range of emergent constraints for ECS.
Western North Pacific Tropical Cyclone Tracks in CMIP5 Models: Statistical Assessment Using a Model-Independent Detection and Tracking Scheme
Authors: Bell Samuel S. , Chand Savin S. , Camargo Suzana J. , Tory Kevin J. , Turville Chris , Ye Harvey 
Published: August 2019

Abstract
Past studies have shown that tropical cyclone (TC) projection results can be sensitive to different types of TC tracking schemes, and that the relative adjustments of detection criteria to accommodate different models may not necessarily provide a consistent platform for comparison of projection results. Here, future climate projections of TC activity in the western North Pacific basin (WNP, defined from 0°–50°N and 100°E–180°) are assessed with a model-independent detection and tracking scheme. This scheme is applied to models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) forced under the historical and representative concentration pathway 8.5 (RCP8.5) conditions. TC tracks from the observed records and independent models are analyzed simultaneously with a curve-clustering algorithm, allowing observed and model tracks to be projected onto the same set of clusters (k = 9). Four of the nine clusters were projected to undergo significant changes in TC frequency. Straight-moving TCs in the South China Sea were projected to significantly decrease. Projected increases in TC frequency were found poleward of 20°N and east of 160°E, consistent with changes in ascending motion, as well as vertical wind shear and relative humidity respectively. Projections of TC track exposure indicated significant reductions for southern China and the Philippines and significant increases for the Korean peninsula and Japan, although very few model TCs reached the latter subtropical regions in comparison to the observations. The use of a fundamentally different detection methodology that overcomes the detector/tracker bias gives increased certainty to projections as best as low-resolution simulations can offer.
Access to Housing Rights and Property Rights for Women: Select Study in Delhi and NCR Regions
Authors: Nanda Bijayalaxmi , Sinha Savita , Menon Venika 
Published: August 2019

This article critically evaluates the housing policies and legal provisions regarding property rights for women in India. It interrogates the inclusion of gender within the policies, programmes and laws, and exposes its biases and skewed priorities. Through a desk review of the policies and programmes and an examination of court judgements, it provides an understanding of the contestations and challenges that exist therein. With carefully conducted interviews and focussed group discussions with women beneficiaries and policy implementers, this article strives to enrich the analysis. It provides a set of suggestions and recommendations on enhancing awareness on women’s right to property and providing women greater access to housing rights. Although the fieldwork has been conducted in Delhi–NCR region, it has implications for the country as a whole. Overall this article contextualises the debates on gender, policy, laws and institutions in a broader framework of material structure s and a patriarchal society. It highlights the significance of creating awareness on gender issues for all concerned, including policymakers, implementers, judiciary and the women beneficiaries themselves.
Information Linkages Among BRICS Countries: Empirical Evidence from Implied Volatility Indices
Authors: Sharma Gagan , Kayal Parthajit , Pandey Piyush 
Published: August 2019

In this article, we examine the information linkages of the forward-looking measure of volatility, the volatility index (VIX), for underlying equity market indices of BRICS countries—Brazil, Russia, India, China and South Africa. A study of the information transmission process confirmed a long-run equilibrium relationship between pairs of BRICS countries. The multivariate generalised autoregressive conditional heteroscedasticity (MGARCH) model revealed strong intertemporal linkages between sample VIX. Return and volatility spill-over matrix show the varying degree of connectedness of BRICS VIX across the study period. This study contributes to the international finance literature and has important implications for investors, portfolio managers, policymakers and academia. JEL Classification: C58, F36, G11, G14, G15