bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the National Emergency Department Overcrowding Score (NEDOCS) in a UK non-specialist emergency department
Authors: Hargreaves Duncan , Snel Sophie , Dewar Colin , Arjan Khushal , Parrella Piervirgilio , Hodgson Luke Eliot 
Published: August 2020

IntroductionEmergency department (ED) crowding has significant adverse consequences, however, there is no widely accepted tool to measure it. This study validated the National Emergency Department Overcrowding score (NEDOCS) (range 0–200 points), which uses routinely collected ED data.MethodsThis prospective single-centre study sampled data during four periods of 2018. The outcome against which NEDOCS performance was assessed was a composite of clinician opinion of crowding (physician and nurse in charge). Area under the receiver operating characteristic curves (AUROCs) and calibration plots were produced. Six-hour stratified sampling was added to adjust for temporal correlation of clinician opinion. Staff inter-rater agreement and NEDOCS association with opinion of risk, safety and staffing levels were collected.ResultsFrom 905 sampled hours, 448 paired observations were obtained, with the ED deemed crowded 18.5% of the time. Inter-rater agreement between staff was moderate (weighted kappa 0.57 (95% CI 0.56 to 0.60)). AUROC for NEDOCS was 0.81 (95% CI 0.77 to 0.86). Adjusted for temporal correlation, AUROC was 0.80 (95% CI 0.73 to 0.88). At a cut-off of 100 points sensitivity was 75.9% (95% CI 65.3% to 84.6%), specificity 72.1% (95% CI 67.1% to 76.6%), positive predictive value 38.2% (95% CI 30.7% to 46.1%) and negative predictive value 92.9% (95% CI 89.3% to 95.6%). NEDOCS underpredicted clinical opinion on Calibration assessment, only partially correcting with intercept updating. For perceived risk of harm, safety and insufficient staffing, NEDOCS AUROCs were 0.71 (95% CI 0.61 to 0.82), 0.71 (95% CI 0.63 to 0.80) and 0.70 (95% CI 0.64 to 0.76), respectively.ConclusionsNEDOCS demonstrated good discriminatory power for clinical perception of crowding. Prior to implementation, determining individual unit ED cut-off point(s) would be important as published thresholds may not be generalisable. Future studies could explore refinement of existing variables or addition of new variables, including acute physiological data, which may improve performance.
Comparison of the efficacy of ketamine– propofol versus sodium thiopental–fentanyl in sedation: a randomised clinical trial
Authors: Bahreini Maryam , Talebi Garekani Mostafa , Sotoodehnia Mehran , Rasooli Fatemeh 
Published: August 2020

BackgroundMany sedative regimens have been studied with controversial efficiencies. This study tried to assess the desirable and adverse effects of sodium thiopental–fentanyl (TF) with ketamine–propofol (KP) for procedural sedation and analgesia in the emergency department.MethodsAfter signing written consent, patients were enrolled in this randomised double-blind trial to receive either KP or TF to reach the desired sedation level. The respiratory and haemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared.ResultsOf the participants, 47 in the KP group and 49 in the TF group were enrolled. The mean and SD scores were 6.91±1.93 and 8.34±1.25 for patients’ satisfaction and 7.55±1.54 and 8.65±1.00 for satisfaction of physicians performing the procedures in TF and KP groups, respectively (p=0.000). Moreover, 39 (79.59%) and 18 (38.29%) of patients declared that they had recalled the procedures in the TF and KP groups, respectively (p=0.000). Transient hypoxia was reported in 2.1% and 8.1% in the KP and TF groups leading to perform 4.2% vs 8.1% airway manoeuvres, respectively, without the need for endotracheal intubation or further admission.ConclusionsKP and TF combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. This study did not detect a difference regarding adverse respiratory or haemodynamic effects. It is estimated that the TF combination can be potent and efficacious with possible low adverse events in procedural sedation.
Epileptic seizures of suspected autoimmune origin: a multicentre retrospective study
Authors: Bozzetti Silvia , Rossini Fabio , Ferrari Sergio , Delogu Rachele , Cantalupo Gaetano , Marchioretto Fabio , Zanette Giampietro , Zanoni Tiziano , Turatti Marco , Vitale Giuseppina , Cadaldini Morena , Rossi Francesca , Di Tizio Luca , Zuco Carmela , Maniscalco Giorgia Teresa , Soldani Fabio , Monaco Salvatore , Trinka Eugen , Hoeftberger Romana , Mariotto Sara 
Published: August 2020

ObjectiveTo analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores.MethodsWe retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data.ResultsAutoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1–15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year.ConclusionsThis is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy.
Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers
Authors: Shen Yao-An , Hong Jiaxin , Asaka Ryoichi , Asaka Shiho , Hsu Fang-Chi , Suryo Rahmanto Yohan , Jung Jin-Gyoung , Chen Yu-Wei , Yen Ting-Tai , Tomaszewski Alicja , Zhang Cissy , Attarwala Nabeel , DeMarzo Angelo M. , Davidson Ben , Chuang Chi-Mu , Chen Xi , Gaillard Stephanie , Le Anne , Shih Ie-Ming , Wang Tian-Li 
Published: August 2020

Abstract

Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression.

Significance:
Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics.
Secreted Factors from Adipose Tissue Reprogram Tumor Lipid Metabolism and Induce Motility by Modulating PPARα/ANGPTL4 and FAK
Authors: Blücher Christina , Iberl Sabine , Schwagarus Nancy , Müller Silvana , Liebisch Gerhard , Höring Marcus , Hidrobo Maria Soledad , Ecker Josef , Spindler Nick , Dietrich Arne , Burkhardt Ralph , Stadler Sonja C. 
Published: August 2020

Abstract

Recent studies indicate that adipose tissue in obesity promotes breast cancer progression by secreting protumorigenic chemokines, growth factors, and fatty acids. However, the detailed mechanisms by which hypertrophic adipose tissue influences breast cancer cells are still not well understood. Here we show that co-culture with adipose tissue from high-fat diet induced obese C57BL/6 mice alters transcriptome profiles in triple-negative breast cancer (TNBC) cells, leading to upregulation of genes involved in inflammation and lipid metabolism, such as IL1B, PLIN2, and ANGPTL4. Similar results were obtained by treating TNBC cells with adipose tissue conditioned media (ACM) generated from fat tissue of obese female patients. Many of the upregulated genes were activated by PPAR nuclear receptors, as shown by pathway analyses and gene expression experiments using PPAR agonists and antagonists. Metabolic analysis revealed that TNBC cells cultivated with ACM had significantly higher levels of β-oxidation. Furthermore, ACM-treated TNBC cells displayed a pronounced aggressive cell phenotype, with enhanced wound healing, proliferation, and invasion capabilities. ACM-induced invasion was dependent on the PPAR-target ANGPTL4 and activated FAK signaling, as shown by ANGPTL4 depletion and FAK inhibition. Together, our data suggest that factors released by adipose tissue change PPAR-regulated gene expression and lipid metabolism and induce a more aggressive TNBC cell phenotype. These effects are, at least in parts, mediated by fatty acids provided by the adipose tissue.

Implications:
Adipose tissue provides factors for increased progression of TNBC cells, identifying PPAR- and FAK-signaling as potential novel targets for treatment of TNBC, especially in obese women.
Systolic Blood Pressure and Longitudinal Progression of Arterial Stiffness: A Quantitative Meta‐Analysis
Authors: Wilson Jack , Webb Alastair John Stewart 
Published: August 2020

Background
Arterial stiffness predicts the risk of cardiovascular events and all‐cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials.

Methods and Results

Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta‐analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026–0.055;
P
<0.001;
P
value for heterogeneity=0.70), equivalent to a 1.14‐m/s increase in standard carotid‐femoral pulse wave velocity per decade per 20–mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004–0.006;
P
<0.001;
P
value for heterogeneity=0.64), equivalent to a 0.94‐m/s increase per decade per 20–mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, −0.008 to 0.086;
P
=0.11;
P
value for heterogeneity=0.03).

Conclusions
Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.
Intelligent Manufacturing Systems in COVID-19 Pandemic and Beyond: Framework and Impact Assessment
Authors: Li Xingyu , Wang Baicun , Liu Chao , Freiheit Theodor , Epureanu Bogdan I. 
Published: August 2020

AbstractPandemics like COVID-19 have created a spreading and ever-higher healthy threat to the humans in the manufacturing system which incurs severe disruptions and complex issues to industrial networks. The intelligent manufacturing (IM) systems are promising to create a safe working environment by using the automated manufacturing assets which are monitored by the networked sensors and controlled by the intelligent decision-making algorithms. The relief of the production disruption by IM technologies facilitates the reconnection of the good and service flows in the network, which mitigates the severity of industrial chain disruption. In this study, we create a novel intelligent manufacturing framework for the production recovery under the pandemic and build an assessment model to evaluate the impacts of the IM technologies on industrial networks. Considering the constraints of the IM resources, we formulate an optimization model to schedule the allocation of IM resources according to the mutual market demands and the severity of the pandemic.
Statement to Kösler et al. 2019 and 2020 regarding the evaluation of the ecotoxicity of nitrification inhibitors using terrestrial and aquatic test organisms
Authors: Pasda Gregor , Schmid Markus 
Published: August 2020

AbstractIn this paper, the correct composition of Vizura is given and a note that the founded results concerning ecotoxicity of Vizura are of no relevance for the recommended application rates for Vizura.
Effects of face-to-face counselling on unemployment rate and duration: evidence from a Public Employment Service reform
Authors: Vehkasalo Ville 
Published: August 2020

AbstractIn a Public Employment Service reform implemented in 2013, sixty Finnish municipalities experienced an involuntary employment office closure. The Government’s objective was to replace traditional face-to-face employment counselling with modern online counselling and simultaneously generate savings in outlays. The reform created natural experiment circumstances that allowed us to estimate the aggregate causal effects of face-to-face counselling and advice. We estimated the effects of the reform on the unemployment rate and the average unemployment duration using municipality-level panel data and various panel data estimators. We found that while the reform had a barely discernible effect on municipal unemployment rates, it increased average unemployment durations by 2–3 weeks. Hence, face-to-face counselling and online counselling are not perfect substitutes in decreasing the length of unemployment spells. Consequently, the fiscal costs of the reform outweigh the fiscal benefits by a large margin.
MCMSeq: Bayesian hierarchical modeling of clustered and repeated measures RNA sequencing experiments
Authors: Vestal Brian E. , Moore Camille M. , Wynn Elizabeth , Saba Laura , Fingerlin Tasha , Kechris Katerina 
Published: August 2020

AbstractBackgroundAs the barriers to incorporating RNA sequencing (RNA-Seq) into biomedical studies continue to decrease, the complexity and size of RNA-Seq experiments are rapidly growing. Paired, longitudinal, and other correlated designs are becoming commonplace, and these studies offer immense potential for understanding how transcriptional changes within an individual over time differ depending on treatment or environmental conditions. While several methods have been proposed for dealing with repeated measures within RNA-Seq analyses, they are either restricted to handling only paired measurements, can only test for differences between two groups, and/or have issues with maintaining nominal false positive and false discovery rates. In this work, we propose a Bayesian hierarchical negative binomial generalized linear mixed model framework that can flexibly model RNA-Seq counts from studies with arbitrarily many repeated observations, can include covariates, and also maintains nominal false positive and false discovery rates in its posterior inference.ResultsIn simulation studies, we showed that our proposed method (MCMSeq) best combines high statistical power (i.e. sensitivity or recall) with maintenance of nominal false positive and false discovery rates compared the other available strategies, especially at the smaller sample sizes investigated. This behavior was then replicated in an application to real RNA-Seq data where MCMSeq was able to find previously reported genes associated with tuberculosis infection in a cohort with longitudinal measurements.ConclusionsFailing to account for repeated measurements when analyzing RNA-Seq experiments can result in significantly inflated false positive and false discovery rates. Of the methods we investigated, whether they model RNA-Seq counts directly or worked on transformed values, the Bayesian hierarchical model implemented in the mcmseq R package (available athttps://github.com/stop-pre16/mcmseq) best combined sensitivity and nominal error rate control.
Dynamics behind disjunct distribution, hotspot-edge refugia, and discordant RADseq/mtDNA variability: insights from the Emei mustache toad
Authors: Zheng Yuchi , Dai Qiang , Guo Xianguang , Zeng Xiaomao 
Published: August 2020

Abstract
Background
The distribution of genetic diversity and the underlying processes are important for conservation planning but are unknown for most species and have not been well studied in many regions. In East Asia, the Sichuan Basin and surrounding mountains constitute an understudied region that exhibits a “ring” of high species richness overlapping the eastern edge of the global biodiversity hotspot Mountains of Southwest China. We examine the distributional history and genetic diversification of the Emei mustache toad Leptobrachium boringii, a typical “ring” element characterized by disjunct ranges in the mountains, by integrating time-calibrated gene tree, genetic variability, individual-level clustering, inference of population splitting and mixing from allele frequencies, and paleoclimatic suitability modeling.

Results
The results reveal extensive range dynamics, including secondary contact after long-term isolation via westward dispersal accompanied by variability loss. They allow the proposal of a model that combines recurrent contractions caused by Quaternary climatic changes and some failed expansions under suitable conditions for explaining the shared disjunct distribution pattern. Providing exceptional low-elevation habitats in the hotspot area, the eastern edge harbors both long-term refugial and young immigrant populations. This finding and a synthesis of evidence from other taxa demonstrate that a certain contributor to biodiversity, one that preserves and receives low-elevation elements of the east in this case, can be significant for only a particular part of a hotspot. By clarifying the low variability of these refugial populations, we show that discordant mitochondrial estimates of diversity can be obtained for populations that experienced admixture, which would have unlikely left proportional immigrant alleles for each locus.

Conclusions
Dispersal after long-term isolation can explain much of the spatial distribution of genetic diversity in this species, while secondary contact and long-term persistence do not guarantee a large variation. The model for the formation of disjunct ranges may apply to many other taxa isolated in the mountains surrounding the Sichuan Basin. Furthermore, this study provides insights into the heterogeneous nature of hotspots and discordant variability obtained from genome-wide and mitochondrial data.
Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction
Authors: Guo Fei , Qiu Xueting , Tan Zhirong , Li Zhenyu , Ouyang Dongsheng 
Published: August 2020

Abstract
Background
Heart failure with preserved ejection fraction (HFpEF) is an emerging global health problem with less awareness. Renal dysfunction in HFpEF is associated with worse outcome. However, there is lack of rapid, noninvasive and accurate method for risk stratification in HFpEF and renal dysfunction. This study aimed to explore the utility of plasma trimethylamine n-oxide (TMAO) for evaluation of HFpEF and renal function.

Methods
Plasma TMAO levels were measured in total 324 subjects comprising 228 HFpEF patients and 96 healthy controls.

Results
TMAO levels were significantly elevated in patients with HFpEF compared with controls (12.65(9.32–18.66) μg/l vs 10.85(6.35–15.58) μg/l, p <  0.01). Subjects in higher TMAO tertile group had more incidences of HFpEF ((78.5%) in tertile 3 vs (73.39%) in tertile 2 vs (59.26%) in tertile 1, p <  0.01). TMAO concentrations were inversely correlated with estimated glomerular filtration rate (eGFR) and HFpEF patients with impaired renal function (eGFR < 60 ml/min/1.73 m2) had higher TMAO than those with normal eGFR (≥ 60 ml/min/1.73 m2) (14.18(10.4–23.06) μg/l vs 10.9(7.48–15.47) μg/l, p < 0.01). Increased TMAO levels were independently associated with higher risk of HFpEF (OR = 3.49, 95% CI: 1.23–9.86, p = 0.02) and renal dysfunction (OR = 9.57, 95% CI: 2.11–43.34, p < 0.01) after adjustment for multiple traditional risk factors. Furthermore, TMAO had good performance at distinguishing HFpEF from controls (AUC = 0.63, p < 0.01), and renal dysfunction from normal renal function in HFpEF (AUC = 0.67, p < 0.01).

Conclusion
In this cross-sectional study, HFpEF and renal function were closely related with plasma TMAO levels and TMAO may serve as a diagnostic biomarker for HFpEF and renal function.
Inference about time-dependent prognostic accuracy measures in the presence of competing risks
Authors: Dey Rajib , Sebastiani Giada , Saha-Chaudhuri Paramita 
Published: August 2020

AbstractBackgroundEvaluating a candidate marker or developing a model for predicting risk of future conditions is one of the major goals in medicine. However, model development and assessment for a time-to-event outcome may be complicated in the presence of competing risks. In this manuscript, we propose a local and a global estimators of cause-specific AUC for right-censored survival times in the presence of competing risks.MethodsThe local estimator - cause-specific weighted mean rank (cWMR) - is a local average of time-specific observed cause-specific AUCs within a neighborhood of given timet. The global estimator - cause-specific fractional polynomials (cFPL) - is based on modelling the cause-specific AUC as a function oftthrough fractional polynomials.ResultsWe investigated the performance of the proposed cWMR and cFPL estimators through simulation studies and real-life data analysis. The estimators perform well in small samples, have minimal bias and appropriate coverage.ConclusionsThe local estimator cWMR and the global estimator cFPL will provide computationally efficient options for assessing the prognostic accuracy of markers for time-to-event outcome in the presence of competing risks in many practical settings.