bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with the occurrence of prehospital medical interventions provided by physicians among non-trauma patients: a single-centre retrospective observational study in Japan
Authors: Abe Tomohiro , Iwatani Kenshi , Aoyama Takeshi , Ameda Tatsunori , Ochiai Hidenobu 
Published: August 2019

ObjectivesPhysician-staffed prehospital units are widely used in many countries. The criteria for predicting fatal injury are well recognised for trauma victims, but there are no criteria for predicting critical condition for non-trauma patients. This study aimed to identify the factors associated with non-trauma cases receiving prehospital interventions by physicians.DesignRetrospective observational study.SettingPhysician-staffed prehospital unit (car) at a single-base hospital in a suburban city in Japan.ParticipantsParticipants were 1058 non-trauma patients who received prehospital medical examinations from April 2014 to December 2017.Outcome measuresThe outcome was the occurrence of physician-only interventions (POIs) exceeding paramedics’ competencies. Univariate analysis and multiple logistic regression analysis were performed. Patient’s age and gender, presumed disease category, type of location of the emergency, time of alarm, activation time, activator’s occupation, time to arrival, transportation time and the destination facility were included as covariates.ResultsPOIs were provided to 380 (36%) patients. Patient’s age, presumed disease category, type of location of the emergency, activator’s occupation, time to arrival, transportation time and the destination facility were identified as potential independent factors. Multiple logistic regression analysis found that patient’s age, presumed disease category, type of location of the emergency, transportation time and destination facility were the significant independent factors. Transportation times of more than 15 min (adjusted ORs (AORs)=4.17, 95% CI 2.59 to 6.72, p<0.01) or 10 to 14 min (AOR=3.66, 95% CI 2.32 to 5.79, p<0.01) and patient age of 40–59 years (AOR=3.16, 95% CI 1.66 to 6.01, p<0.01) were the strongest independent factors.ConclusionsThis study identified the factors associated with non-trauma cases receiving prehospital POIs. Patient’s age, presumed disease category, type of location of the emergency and transportation time are independent factors associated with requiring POIs.
Identification of risk factors affecting catch-up growth after infant congenital heart disease surgery: rationale and design of a multicentre prospective cohort study in China
Authors: Li Lijuan , LI Kuanrong , An Caixia , Fan Jiajie , Guo Changying , Liang Suixin , Guo Yue , Xia Huimin , Chen Xinxin , Zhu Yanna , Hu Chunmei , Si Wenyue , Liang Huiying , Cui Yanqin 
Published: August 2019

IntroductionSuccessful surgical treatment of congenital heart disease improves neonates’ long-term survival and leads to catch-up growth, which however does not occur in part of the patient population for largely undetermined reasons.Methods and analysisA multicentre, prospective cohort study is being conducted in four paediatric medical institutions in China to collect detailed nutritional, anthropometric and clinical data at perioperative phases and during a 1-year period of follow-up after surgery. The study is expected to recruit approximately 5000 patients by the year of 2023 when the cohort is fully established. The primary endpoint of this study is the occurrence of postoperative catch-up growth, which will be determined in both absolute and relative terms (ie, reduced anthropometric deficits from the reference measures and improved z-scores that have passed the −2 SD cut-offs). Multivariable regression analyses will be performed to identify factors that are statistically significantly associated with the absence of postoperative catch-up growth.Ethics and disseminationThe protocol of this study has been approved by the individual ethics committees of the participating centres (Guangzhou Women and Children’s Medical Centre (2008071601), the Children’s Hospital of Zhejiang University School of Medicine (2018-IRB-094), Gansu Provincial Maternity and Child-Care Hospital (2019-IRB-01) and Zhengzhou Cardiovascular Hospital (2019012001)). Written informed consent from parents will be obtained before study entry. Findings of this study will be disseminated through publications in international peer-reviewed journals and will be presented in academic conferences.
Study protocol for a randomised controlled trial with clinical, neurophysiological, laboratory and radiological outcome for surgical versus non-surgical treatment for lumbar spinal stenosis: the Uppsala Spinal Stenosis Trial (UppSten)
Authors: Pazarlis Konstantinos , Punga Anna , Schizas Nikos , Sandén Bengt , Michaëlsson Karl , Försth Peter 
Published: August 2019

IntroductionSymptomatic lumbar spinal stenosis is the most common indication for spinal surgery. However, more than one-third of the patients undergoing surgery for lumbar stenosis report dissatisfaction with the results. On the other hand, conservative treatment has shown positive results in some cases. This trial will compare the outcomes of surgical versus non-surgical treatment for lumbar stenosis. The study includes a multidimensional follow-up, aiming to study the association between outcome and other studied parameters, mainly electromyography and nerve conduction. Moreover, it may contribute to a better understanding of the pathophysiology of lumbar stenosis and to the development of future pharmacological treatments.Methods and analysisUppSten is a single-centre randomised controlled trial in which 150 patients with symptomatic lumbar spinal stenosis will be randomised into one of two treatment arms. The patients in the surgical arm will undergo laminectomy; the patients in the non-surgical arm will be given a structured physical training programme. The primary outcome of the study will be the Oswestry Disability Index. Secondary outcomes will include motor amplitude and degree of denervation activity obtained by means of nerve conduction studies and electromyography. Patient-reported outcome measures will be also used as secondary outcomes. Blood sample analysis and the investigation of potential inflammation markers are the additional secondary outcome parameters. Laboratory evaluation will include blood sample collection before the treatment initiation and after 6 months. Flavum ligament biopsies will be performed in the surgical group. Finally, tertiary outcomes will include neurophysiological measures, the objective walking ability and radiological evaluation.Ethics and disseminationThe study is approved by the Local Ethics Committee (Dnr 2017–506), the Hospital’s Clinical Trials Committee (2018–0001) and the National Biobank Council and Uppsala Biobank (BbA-827-2018-025). The results will be presented in peer-reviewed journals and at international conferences.Trial registration numberNCT03495661
Identification of influenza urban transmission patterns by geographical, epidemiological and whole genome sequencing data: protocol for an observational study
Authors: Egli Adrian , Saalfrank Claudia , Goldman Nina , Brunner Myrta , Hollenstein Yvonne , Vogel Thomas , Augustin Noémie , Wüthrich Daniel , Seth-Smith Helena M.B. , Roth Elisa , Syedbasha Mohammedyaseen , Mueller Nicola F. , Vogt Dominik , Bauer Jan , Amar-Sliwa Nadezhda , Meinel Dominik M. , Dubuis Olivier , Naegele Michael , Tschudin-Sutter Sarah , Buser Andreas , Nickel Christian H. , Zeller Andreas , Ritz Nicole , Battegay Manuel , Stadler Tanja , Schneider-Sliwa Rita 
Published: August 2019

IntroductionUrban transmission patterns of influenza viruses are complex and poorly understood, and multiple factors may play a critical role in modifying transmission. Whole genome sequencing (WGS) allows the description of patient-to-patient transmissions at highest resolution. The aim of this study is to explore urban transmission patterns of influenza viruses in high detail by combining geographical, epidemiological and immunological data with WGS data.Methods and analysisThe study is performed at the University Hospital Basel, University Children’s Hospital Basel and a network of paediatricians and family doctors in the Canton of Basel-City, Switzerland. The retrospective study part includes an analysis of PCR-confirmed influenza cases from 2013 to 2018. The prospective study parts include (1) a household survey regarding influenza-like illness (ILI) and vaccination against influenza during the 2015/2016 season; (2) an analysis of influenza viruses collected during the 2016/2017 season using WGS—viral genomic sequences are compared with determine genetic relatedness and transmissions; and (3) measurement of influenza-specific antibody titres against all vaccinated and circulated strains during the 2016/2017 season from healthy individuals, allowing to monitor herd immunity across urban quarters. Survey data and PCR-confirmed cases are linked to data from the Statistics Office of the Canton Basel-City and visualised using geo-information system mapping. WGS data will be analysed in the context of patient epidemiological data using phylodynamic analyses, and the obtained herd immunity for each quarter. Profound knowledge on the key geographical, epidemiological and immunological factors influencing urban influenza transmission will help to develop effective counter measurements.Ethics and disseminationThe study is registered and approved by the regional ethics committee as an observational study (EKNZ project ID 2015–363 and 2016–01735). It is planned to present the results at conferences and publish the data in scientific journals.Trial registration numberNCT03010007.
Effect of vitamin E in non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomised controlled trials
Authors: Amanullah Iram , Khan Yusra Habib , Anwar Iqraa , Gulzar Aqsa , Mallhi Tauqeer Hussain , Raja Ahsan Aftab 
Published: August 2019

AbstractThe efficacy of vitamin E among patients with non-alcoholic fatty liver disease (NAFLD) is unclear. The current qualitative and quantitative analyses aimed to ascertain the efficacy of vitamin E on clinical outcomes of patients with NAFLD. A systematic search of randomised controlled trials (RCTs) was performed using databases (PubMed, ProQuest, Scopus, EBSCOhost and Ovid) from inception to July 2018. Trials meeting the inclusion criteria were subjected to quality assessment using the Jadad Scoring. All trials meeting the prerequisites information for meta-analysis were subjected to quantitative synthesis of results. Nine RCTs (five in adults and four in children) were included. Four of the five RCTs on adults demonstrated significant improvements in alanine transaminase and other liver function surrogates in patients with NAFLD. On the other hand, only one of the four RCTs conducted on children showed significant improvements in liver functions with the use of vitamin E. Although quantitative synthesis of available data revealed insignificant differences between vitamin E and placebo, still the use of vitamin E improves the level of alanine transaminase and aspartate transaminase by −1.96 and −0.59, with heterogeneity of I2=67% and I2=0%, respectively. Adjuvant vitamin E therapy provides significant biochemical and histological improvements in adult patients with NAFLD, while paediatric patients showed insignificant efficacy compared with placebo. Lifestyle interventions along with vitamin E can provide much better results. Data, including the impact of vitamin E on hepatic histology, are still lacking. Moreover, the short duration of trials limits the conclusion on the safety and efficacy of proposed treatments.
Prospects for heavy scalar searches at the LHeC
Authors: Rose Luigi Delle , Fischer Oliver , Hammad A. 
Published: August 2019

In this paper, we study the prospects of the proposed Large Hadron electron Collider (LHeC) in the search for heavy neutral scalar particles. We consider a minimal model with one additional complex scalar singlet that interacts with the Standard Model (SM) via mixing with the Higgs doublet, giving rise to an SM-like Higgs boson [Formula: see text] and a heavy scalar particle [Formula: see text]. Both scalar particles are produced via vector boson fusion and can be tested via their decays into pairs of SM particles, analogously to the SM Higgs boson. Using multivariate techniques, we show that the LHeC is sensitive to [Formula: see text] with masses between 200 and 800 GeV down to scalar mixing of [Formula: see text].
Generators of the quantum finite W-algebras in type A
Authors: De Sole Alberto , Fedele Laura , Valeri Daniele 
Published: August 2019

We prove a conjecture proposed in [A. De Sole, V. G. Kac and D. Valeri, Finite [Formula: see text]-algebras for [Formula: see text], Adv. Math. 327 (2018) 173–224.] describing the Lax type operator [Formula: see text] for the quantum finite [Formula: see text]-algebras of [Formula: see text] in terms of a PBW generating system for the [Formula: see text]-algebra. In doing so, we extend this result to an arbitrary good grading and an arbitrary isotropic subspace of [Formula: see text].
Diffusion models for mixtures using a stiff dissipative hyperbolic formalism
Authors: Boudin Laurent , Grec Bérénice , Pavan Vincent 
Published: August 2019

We consider a system of fluid equations for mixtures with a stiff relaxation term of Maxwell–Stefan diffusion type. We use the formalism developed by Chen et al. and derive a limiting system of Fick type, in which the species velocities tend to align with a bulk velocity when the relaxation parameter remains small.
Optimizing Bit-Serial Matrix Multiplication for Reconfigurable Computing
Authors: Umuroglu Yaman , Conficconi Davide , Rasnayake Lahiru , Preusser Thomas B. , Själander Magnus 
Published: August 2019

Matrix-matrix multiplication is a key computational kernel for numerous applications in science and engineering, with ample parallelism and data locality that lends itself well to high-performance implementations. Many matrix multiplication-dependent applications can use reduced-precision integer or fixed-point representations to increase their performance and energy efficiency while still offering adequate quality of results. However, precision requirements may vary between different application phases or depend on input data, rendering constant-precision solutions ineffective. BISMO, a vectorized bit-serial matrix multiplication overlay for reconfigurable computing, previously utilized the excellent binary-operation performance of FPGAs to offer a matrix multiplication performance that scales with required precision and parallelism. We show how BISMO can be scaled up on Xilinx FPGAs using an arithmetic architecture that better utilizes six-input LUTs. The improved BISMO achieves a peak performance of 15.4 binary TOPS on the Ultra96 board with a Xilinx UltraScale+ MPSoC.
Enteroids expressing a disease-associated mutant of EpCAM are a model for congenital tufting enteropathy
Authors: Das Barun , Okamoto Kevin , Rabalais John , Kozan Philip A. , Marchelletta Ronald R. , McGeough Matthew D. , Durali Nassim , Go Maria , Barrett Kim E. , Das Soumita , Sivagnanam Mamata 
Published: August 2019

Congenital tufting enteropathy (CTE) is an autosomal recessive disease characterized by severe intestinal failure in infancy and mutations in the epithelial cell adhesion molecule ( EPCAM) gene. Previous studies of CTE in mice expressing mutant EpCAM show neonatal lethality. Hence, to study the cellular, molecular, and physiological alterations that result from EpCAM mutation, a tamoxifen-inducible mutant EpCAM enteroid model has been generated. The presence of mutant EpCAM in the model was confirmed at both mRNA and protein levels. Immunofluorescence microscopy demonstrated the reduced expression of mutant EpCAM. Mutant enteroids had reduced budding potential as well as significantly decreased mRNA expression for epithelial lineage markers ( Mucin 2, lysozyme, sucrase-isomaltase), proliferation marker Ki67, and secretory pathway transcription factors ( Atoh1, Hnf1b). Significantly decreased numbers of Paneth and goblet cells were confirmed by staining. These findings were correlated with intestinal tissue from CTE patients and the mutant mice model that had significantly fewer Paneth and goblet cells than in healthy counterparts. FITC-dextran studies demonstrated significantly impaired barrier function in monolayers derived from mutant enteroids compared with control monolayers. In conclusion, we have established an ex vivo CTE model. The role of EpCAM in the budding potential, differentiation, and barrier function of enteroids is noted. Our study establishes new facets of EpCAM biology that will aid in understanding the pathophysiology of CTE and role of EpCAM in health and disease. NEW & NOTEWORTHY Here, we develop a novel ex vivo enteroid model for congenital tufting enteropathy (CTE) based on epithelial cell adhesion molecule ( EPCAM) gene mutations found in patients. With this model we demonstrate the role of EpCAM in maintaining the functional homeostasis of the intestinal epithelium, including differentiation, proliferation, and barrier integrity. This study further establishes a new direction in EpCAM biology that will help in understanding the detailed pathophysiology of CTE and role of EpCAM.
The Cdk2–c-Myc–miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin
Authors: Zhang Yi , Li Zhuqing , Hao Qiang , Tan Wei , Sun Jing , Li Jing , Chen Chi-wei , Li Zongzhu , Meng Yunxiao , Zhou Yuan , Han Zhiyong , Pei Huadong , DePamphilis Melvin L. , Zhu Wenge 
Published: August 2019

AbstractDNA rereplication leads to genomic instability and has been implicated in the pathology of a variety of human cancers. Eukaryotic DNA replication is tightly controlled to ensure it occurs only once during each cell cycle. Geminin is a critical component of this control, it prevents DNA rereplication from occurring during S, G2, and early M phases by preventing MCM helicases from forming prereplication complexes. Geminin is targeted for degradation by the anaphase-promoting complex (APC/C) from anaphase through G1-phase, however, accumulating evidence indicates that Geminin is downregulated in late S-phase due to an unknown mechanism. Here, we used a high-throughput screen to identify miRNAs that can induce excess DNA replication and found that miR-571 could reduce the protein level of Geminin in late S-phase independent of the APC/C. Furthermore, miR-571 regulated efficient DNA replication and S-phase cell-cycle progression. Strikingly, c-Myc suppressed miR-571 expression by binding directly to the miR-571 promoter. At the beginning of S-phase, Cdk2 phosphorylated c-Myc at Serine 62, promoting its association with the miR-571 promoter region. Collectively, we identify miR-571 as the first miRNA that prevents aberrant DNA replication and the Cdk2–c-Myc–miR-571 axis as a new pathway for regulating DNA replication, cell cycle, and genomic stability in cancer cells.Significance:These findings identify a novel regulatory mechanism that is critical for maintaining genome integrity by regulating DNA replication and cell-cycle progression.
MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1
Authors: Chuang Huai-Chia , Chang Chih-Chi , Teng Chiao-Fang , Hsueh Chia-Hsin , Chiu Li-Li , Hsu Pu-Ming , Lee Ming-Ching , Hsu Chung-Ping , Chen Yi-Rong , Liu Yi-Chung , Lyu Ping-Chiang , Tan Tse-Hua 
Published: August 2019

AbstractOverexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1.Significance:These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.
A Tumor Agnostic Therapeutic Strategy for Hexokinase 1–Null/Hexokinase 2–Positive Cancers
Authors: Xu Shili , Herschman Harvey R. 
Published: August 2019

Abstract
Since Warburg's observation that most cancers exhibit elevated glycolysis, decades of research have attempted to reduce tumor glucose utilization as a therapeutic approach. Hexokinase (HK) activity is the first glycolytic enzymatic step; despite many attempts to inhibit HK activity, none has reached clinical application. Identification of HK isoforms, and recognition that most tissues express only HK1 while most tumors express HK1 and HK2, stimulated reducing HK2 activity as a therapeutic option. However, studies using HK2 shRNA and isogenic HK1+HK2− and HK1+HK2+ tumor cell pairs demonstrated that tumors expressing only HK1, while exhibiting reduced glucose consumption, progressed in vivo as well as tumors expressing both HK1 and HK2. However, HK1−HK2+ tumor subpopulations exist among many cancers. shRNA HK2 suppression in HK1−HK2+ liver cancer cells reduced xenograft tumor progression, in contrast to HK1+HK2+ cells. HK2 inhibition, and partial inhibition of both oxidative phosphorylation and fatty acid oxidation using HK2 shRNA and small-molecule drugs, prevented human liver HK1−HK2+ cancer xenograft progression. Using human multiple myeloma xenografts and mouse allogeneic models to identify potential clinical translational agents, triple therapies that include antisense HK2 oligonucleotides, metformin, and perhexiline prevent progression. These results suggest an agnostic approach for HK1−HK2+ cancers, regardless of tissue origin.