bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ulcerative colitis outcomes research in Japan: protocol for an observational prospective cohort study of YOURS (YOu and Ulcerative colitis: Registry and Social network)
Authors: Yamazaki Hajime , Matsuoka Katsuyoshi , Fernandez Jovelle , Hibi Toshifumi , Watanabe Mamoru , Hisamatsu Tadakazu , Fukuhara Shunichi 
Published: September 2019

IntroductionUlcerative colitis (UC) is a chronic inflammatory disease that mainly affects the colon in young patients. Typical symptoms of UC are bloody diarrhoea and faecal urgency, which disturb the quality of life (QOL) of patients, and intractable UC leads to hospitalisation and colectomy. To improve relevant outcomes such as symptoms, QOL and colectomy, many clinical questions need to be resolved regarding what the ideal lifestyle, psychosocial burden and optimal practice patterns are. In this YOu and Ulcerative colitis: Registry and Social network (YOURS) study, we will investigate the effect of lifestyle, psychosocial factors and practice patterns on patient-reported outcomes (PRO), hospitalisation rate and colectomy rate in Japanese patients with UC.Methods and analysisFor this prospective cohort study, we recruited 2006 patients from five hospitals (Tokyo and Chiba; May 2018–January 2019). Patients will be able to access their own data and compare them with summarised data from all patients on the website beyond the YOURS study. At baseline, patients will answer a questionnaire regarding lifestyle (diet, exercise, sleep and work), psychosocial factors (stress, depression and social support) and PRO (symptoms and QOL). Information on practice patterns (eg, medications, endoscopy frequency) will be collected from electronic medical records. Gaps between patients’ needs and healthcare professionals’ practice will be identified. Follow-up surveys will be conducted periodically for approximately 3 years. Research questions suggested by patients and healthcare professionals may be used in subsequent surveys. Results from the YOURS study will demonstrate optimal UC management strategies to improve relevant outcomes.The study was approved by the ethics committees of five investigational sites before starting the study. The results will be submitted to journals.UMIN000031995.
Risk factors for progression of carotid intima-media thickness in patients with systemic lupus erythematosus: protocol for an observational cohort study in China
Authors: Pang Haiyu , Ye Yicong , Ding Faming , Li Mengtao , Yang Xinglin , Yang Xufei , Wang Qian , Xu Dong , Fei Yunyun , Kang Lin , Zeng Xiaofeng , Zhang Shuyang 
Published: September 2019

IntroductionAccelerated atherosclerosis is a major complication of systemic lupus erythematosus (SLE), and it leads to increased cardiovascular morbidity and mortality in patients with SLE. This study aimed to investigate the natural progression of carotid intima-media thickness (CIMT), and to examine the risk factors for progression of CIMT and atherosclerotic plaques based on a Chinese SLE cohort.Methods and analysisParticipants were continuously enrolled as outpatients of the Department of Rheumatology in Peking Union Medical College Hospital (PUMCH) from October 2013 to December 2016. Inclusion criteria were as follows: (1) age ≥18 years, (2) fulfilment of clinical classification criteria of SLE and (3) provision of signed written informed consent. Patients with clinically overt coronary artery disease, a history of cardiovascular disease (previous stroke, heart failure, myocardial infarction, angina or symptomatic peripheral artery disease) and malignancy, and pregnant/lactating women were excluded. The primary outcome is progression of CIMT from baseline. A total of 440 patients with SLE will be enrolled. Participants will receive follow-up surveys ~5 years after their baseline visit. A standard structural survey form, including demographic data, medical history, clinical and laboratory assessments and CIMT measurement, is planned for data collection at baseline and follow-up. The risk prediction model for progression of CIMT will be created by using a mixed effect model.Ethics and disseminationThe study protocol was approved by the institutional review board of PUMCH (S-599). Informed consent was obtained from all participants according to the Declaration of Helsinki on Biomedical Research Involving Human Studies. All data will be managed confidentially according to guidelines and legislation. Dissemination will include publication of scientific papers and/or presentations of the study findings at international conferences.
Protocol for a multisite randomised trial of Hand–Arm Bimanual Intensive Training Including Lower Extremity training for children with bilateral cerebral palsy: HABIT-ILE Australia
Authors: Sakzewski Leanne , Bleyenheuft Yannick , Boyd Roslyn N , Novak Iona , Elliott Catherine , Reedman Sarah , Morgan Cathy , Pannek Kerstin , Fripp Jurgen , Golland Prue , Rowell David , Chatfield Mark , Ware Robert Stuart 
Published: September 2019

IntroductionChildren with bilateral cerebral palsy often experience difficulties with posture, gross motor function and manual ability, impacting independence in daily life activities, participation and quality of life (QOL). Hand–Arm Bimanual Intensive Training Including Lower Extremity (HABIT-ILE) is a novel intensive motor intervention integrating upper and lower extremity training. This study aimed to compare HABIT-ILE to usual care in a large randomised controlled trial (RCT) in terms of gross motor function, manual ability, goal attainment, walking endurance, mobility, self-care and QOL. A within-trial cost–utility analysis will be conducted to synthesise costs and benefits of HABIT-ILE compared with usual care.Methods and analysis126 children with bilateral cerebral palsy aged 6–16 years will be recruited across three sites in Australia. Children will be stratified by site and Gross Motor Function Classification System and randomised using concealed allocation to either receiving HABIT-ILE immediately or being waitlisted for 26 weeks. HABIT-ILE will be delivered in groups of 8–12 children, for 6.5 hours per day for 10 days (total 65 hours, 2 weeks). Outcomes will be assessed at baseline, immediately following intervention, and then retention of effects will be tested at 26 weeks. Primary outcomes will be the Gross Motor Function Measure and ABILHAND-Kids. Secondary outcomes will be brain structural integrity, walking endurance, bimanual hand performance, self-care, mobility, performance and satisfaction with individualised goals, and QOL. Analyses will follow standard principles for RCTs using two-group comparisons on all participants on an intention-to-treat basis. Comparisons between groups for primary and secondary outcomes will be conducted using regression models.Ethics and disseminationEthics approval has been granted by the Medical Research Ethics Committee of Children’s Health Queensland Hospital and the Health Service Human Research Ethics Committee (HREC/17/QRCH/282) of The University of Queensland (2018000017/HREC/17/QRCH/2820), and The Cerebral Palsy Alliance Ethics Committee (2018_04_01/HREC/17/QRCH/282).Trial registration numberACTRN12618000164291.
Mortality and potential years of life lost attributable to non-optimal glycaemic control in men and women with diabetes in the United Arab Emirates: a population-based retrospective cohort study
Authors: Al-Shamsi Saif , Govender Romona Devi , Soteriades Elpidoforos S 
Published: September 2019

ObjectivesNumerous studies reported that achieving near-normal glycated haemoglobin (HbA1c) levels in patients with diabetes may delay or even prevent vascular complications. However, information regarding the impact of non-optimal HbA1c control on adverse health outcomes in an Arab population is unknown. The aim of this study was to estimate the fraction of deaths and potential years of life lost (PYLL) attributable to non-optimal HbA1c control among Emirati men and women with diabetes in the United Arab Emirates (UAE).DesignA retrospective cohort study.SettingThis study was conducted in outpatient clinics at a tertiary care centre in Al Ain, UAE, between April 2008 and September 2018.ParticipantsThe sample comprised of 583 adult UAE nationals, aged≥18 years, with diabetes. Overall, 57% (n=332) of the study participants were men and 43% (n=251) were women.ExposureNon-optimal HbA1c control, defined as HbA1c≥6.5%.Primary outcome measureAll-cause mortality, defined as death from any cause.ResultsAt the end of the 9-year follow-up period, 86 (14.8%) participants died. Overall, up to 33% (95% CI 2% to 63%) of deaths were attributable to non-optimal HbA1c control among patients with diabetes mellitus (DM). Stratified by sex, the adjusted fraction of avoidable mortality was 17% (95% CI −23% to 57%) for men and 50% (95% CI 3% to 98%) for women. Both deaths and PYLL attributable to non-optimal HbA1c control were higher in women compared with men.ConclusionsUp to one-third of all deaths in adult UAE nationals with DM could be attributed to non-optimal HbA1c control. Effective sex-specific interventions and healthcare quality‐improvement programmes should urgently be implemented.
Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface
Authors: Koach Jessica , Holien Jessica K. , Massudi Hassina , Carter Daniel R. , Ciampa Olivia C. , Herath Mika , Lim Taylor , Seneviratne Janith A. , Milazzo Giorgio , Murray Jayne E. , McCarroll Joshua A. , Liu Bing , Mayoh Chelsea , Keenan Bryce , Stevenson Brendan W. , Gorman Michael A. , Bell Jessica L. , Doughty Larissa , Hüttelmaier Stefan , Oberthuer Andre , Fischer Matthias , Gifford Andrew J. , Liu Tao , Zhang Xiaoling , Zhu Shizhen , Gustafson W. Clay , Haber Michelle , Norris Murray D. , Fletcher Jamie I. , Perini Giovanni , Parker Michael W. , Cheung Belamy B. , Marshall Glenn M. 
Published: September 2019

Abstract

MYCN is a major driver for the childhood cancer, neuroblastoma, however, there are no inhibitors of this target. Enhanced MYCN protein stability is a key component of MYCN oncogenesis and is maintained by multiple feedforward expression loops involving MYCN transactivation target genes. Here, we reveal the oncogenic role of a novel MYCN target and binding protein, proliferation-associated 2AG4 (PA2G4). Chromatin immunoprecipitation studies demonstrated that MYCN occupies the PA2G4 gene promoter, stimulating transcription. Direct binding of PA2G4 to MYCN protein blocked proteolysis of MYCN and enhanced colony formation in a MYCN-dependent manner. Using molecular modeling, surface plasmon resonance, and mutagenesis studies, we mapped the MYCN–PA2G4 interaction site to a 14 amino acid MYCN sequence and a surface crevice of PA2G4. Competitive chemical inhibition of the MYCN–PA2G4 protein–protein interface had potent inhibitory effects on neuroblastoma tumorigenesis in vivo. Treated tumors showed reduced levels of both MYCN and PA2G4. Our findings demonstrate a critical role for PA2G4 as a cofactor in MYCN-driven neuroblastoma and highlight competitive inhibition of the PA2G4-MYCN protein binding as a novel therapeutic strategy in the disease.

Significance:
Competitive chemical inhibition of the PA2G4–MYCN protein interface provides a basis for drug design of small molecules targeting MYC and MYCN-binding partners in malignancies driven by MYC family oncoproteins.
Left Main Coronary Artery Disease Revascularization According to the SYNTAX Score
Authors: Shlofmitz Evan , Généreux Philippe , Chen Shmuel , Dressler Ovidiu , Ben-Yehuda Ori , Morice Marie-Claude , Puskas John D. , Taggart David P. , Kandzari David E. , Crowley Aaron , Redfors Björn , Mehdipoor Ghazaleh , Kappetein Arie Pieter , Sabik Joseph F. , Serruys Patrick W. , Stone Gregg W. 
Published: September 2019

Background:
The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS), a measure of anatomic coronary artery disease (CAD) extent and complexity, has proven useful in past studies to determine the absolute and relative prognosis after revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We sought to assess contemporary outcomes after PCI and CABG in patients with left main CAD according to SS and revascularization type from a large randomized trial.

Methods:
The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and site-assessed SS≤32 to PCI with everolimus-eluting stents or CABG. Four-year outcomes were examined according to angiographic core laboratory–assessed SS using multivariable Cox proportional hazards regression.

Results:

A total of 1840 patients with left main CAD randomized to PCI (n=914) versus CABG (n=926) had angiographic core laboratory SS assessment. The mean SS was 26.5±9.3 (range 5–74); 24.1% of patients had angiographic core laboratory–assessed SS ≥33. The 4-year rate of the primary major adverse cardiac event end point of death, stroke, or myocardial infarction was similar between PCI and CABG (18.6% versus 16.7%, respectively;
P
=0.40) and did not vary according to SS (
P
interaction
=0.33). Rates of ischemia-driven revascularization rose with increasing SS after PCI, but not after CABG. As a result, the major secondary composite end point of major adverse cardiac or cerebrovascular events (major adverse cardiac event or ischemia-driven revascularization) occurred more frequently with PCI than CABG (28.0% versus 22.0%,
P
=0.01), a difference which rose progressively with increasing SS (
P
interaction
=0.03).

Conclusions:
In the EXCEL trial, the 4-year primary composite major adverse cardiac event end point of death, myocardial infarction, or stroke was similar after PCI with everolimus-eluting stents and CABG and was independent of the baseline anatomic complexity and extent of CAD. In contrast, the relative and absolute hazard of major adverse cardiac or cerebrovascular events with PCI compared with CABG rose progressively with the SS. These data should be considered by the heart team when deciding between PCI versus CABG for revascularization in patients with left main CAD.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier NCT01205776.
Taking Herod to Task: Source Critical and New Historical Methods of Reading Herod’s Trial
Authors: Finkelstein Ari 
Published: September 2019

AbstractFor nearly three decades scholars of the first-century Jewish historian, Flavius Josephus, have debated this author’s methodologies and goals in writing his Jewish Antiquities. While source-critics view Josephus as a compiler, new historians have chosen to read Antiquities as primarily a literary work which reveals social, political, and intellectual history. A series of recent publications place these methodologies side by side but rarely coordinate them, which leaves out important insights of each group. At stake is how we moderns read Jewish history of the first century CE. I explore how parallel accounts of Herod’s trial while he was Tetrarch of the Galilee in Jewish War and in Antiquities can be justified by employing source-critical analysis as a first step to explain the changes made to the text of Antiquities before turning to new historians’ methodologies. We can better understand the function of Herod’s trial in Antiquities through this process.
<p><strong><em>Aloidendron</em></strong><strong> (Asphodelaceae subfam. Alooideae) consists of six species, not seven: <em>Aloe sabaea</em> is a true aloe</strong></p>
Authors: SMITH GIDEON F. , KLOPPER RONELL R. , GRACE OLWEN M. 
Published: September 2019

As part of a revised generic classification of Aloe Linnaeus (1753: 319) sensu lato (Grace et al. 2013), Aloidendron (Berger 1905: 56) Klopper & Gideon F.Sm. in Grace et al. (2013: 9) was established to accommodate six tree aloe species that Berger (1905) previously placed in two sections, Aloe sect. Aloidendron Berger (1905: 56) and A. sect. Dracoaloë Berger (1905: 56). The six species transferred to Aloidendron were: A. barberae (Dyer 1874: 566) Klopper & Gideon F. Sm. in Grace et al. (2013: 9), A. dichotomum (Masson 1776: 310) Klopper & Gideon F.Sm. in Grace et al. (2013: 9), A. eminens (Reynolds & Bally 1958: 187) Klopper & Gideon F.Sm. in Grace et al. (2013: 9), A. pillansii (Guthrie 1928: 15) Klopper & Gideon F.Sm. in Grace et al. (2013: 9), A. ramosissimum (Pillans 1939: 66) Klopper & Gideon F.Sm. in Grace et al. (2013: 9), and A. tongaense (Van Jaarsveld 2010: 71) Klopper & Gideon F.Sm. in Grace et al. (2013: 10). These tree aloes, but not A. sabaeum (Schweinf.) Boatwr. & J.C.Manning in Manning et al. (2014: 67) (see next paragraph), have been treated by Van Jaarsveld & Judd (2015).
Structural characterization of self-assembled chain like Fe-FeOx Core shell nanostructure
Authors: Mukhtar Aiman , Cao Xiao-Ming , Mehmood Tahir , Wang Da-shuang , Wu Kai-ming 
Published: September 2019

Abstract
One of the big challenge of studying the core-shell iron nanostructures is to know the nature of oxide shell, i.e., whether it is γ-Fe2O3 (Maghemite), Fe3O4 (Magnetite), α-Fe2O3 (Hematite), or FeO (Wustite). By knowing the nature of iron oxide shell with zero valent iron core, one can determine the chemical or physical behavior of core-shell nanostructures. Fe core-shell nanochains (NCs) were prepared through the reduction of Fe3+ ions by sodium boro-hydride in aqueous solution at room atmosphere, and Fe NCs were further aged in water up to 240 min. XRD was used to study the structure of Fe NCs. Further analysis of core-shell nature of Fe NCs was done by TEM, results showed increase in thickness of oxide shell (from 2.5, 4, 6 to 10 nm) as water aging time increases (from 0 min, 120 min, 240 min to 360 min). The Raman spectroscopy was employed to study the oxide nature of Fe NCs. To further confirm the magnetite phase in Fe NCs, the Mössbauer spectroscopy was done on Fe NCs-0 and Fe NCs-6. Result shows the presence of magnetite in the sample before aging in water, and the sample after prolonged aging contains pure Hematite phase. It shows that prolonged water oxidation transforms the structure of shell of Fe NCs from mixture of Hematite and Magnetite in to pure hematite shell. The Magnetic properties of the Fe NCs were measured by VSM at 320 K. Because of high saturation magnetization (Ms) values, Fe NCs could be used as r2 contrasts agents for magnetic resonance imaging (MRI) in near future.
nanite: using machine learning to assess the quality of atomic force microscopy-enabled nano-indentation data
Authors: Müller Paul , Abuhattum Shada , Möllmert Stephanie , Ulbricht Elke , Taubenberger Anna V. , Guck Jochen 
Published: September 2019

AbstractBackgroundAtomic force microscopy (AFM) allows the mechanical characterization of single cells and live tissue by quantifying force-distance (FD) data in nano-indentation experiments. One of the main problems when dealing with biological tissue is the fact that the measured FD curves can be disturbed. These disturbances are caused, for instance, by passive cell movement, adhesive forces between the AFM probe and the cell, or insufficient attachment of the tissue to the supporting cover slide. In practice, the resulting artifacts are easily spotted by an experimenter who then manually sorts out curves before proceeding with data evaluation. However, this manual sorting step becomes increasingly cumbersome for studies that involve numerous measurements or for quantitative imaging based on FD maps.ResultsWe introduce the Python packagenanite, which automates all basic aspects of FD data analysis, including data import, tip-sample separation, base line correction, contact point retrieval, and model fitting. In addition,naniteenables the automation of the sorting step using supervised learning. This learning approach relates subjective ratings to predefined features extracted from FD curves. For ratings ranging from 0 to 10, our approach achieves a mean squared error below 1.0 rating points and a classification accuracy between good and poor curves that is above 87%. We showcase our approach by quantifying Young’s moduli of the zebrafish spinal cord at different classification thresholds and by introducing data quality as a new dimension for quantitative AFM image analysis.ConclusionThe addition of quality-based sorting using supervised learning enables a fully automated and reproducible FD data analysis pipeline for biological samples in AFM.
HPAanalyze: an R package that facilitates the retrieval and analysis of the Human Protein Atlas data
Authors: Tran Anh Nhat , Dussaq Alex M. , Kennell Timothy , Willey Christopher D. , Hjelmeland Anita B. 
Published: September 2019

Abstract

Background
The Human Protein Atlas (HPA) aims to map human proteins via multiple technologies including imaging, proteomics and transcriptomics. Access of the HPA data is mainly via web-based interface allowing views of individual proteins, which may not be optimal for data analysis of a gene set, or automatic retrieval of original images.

Results
HPAanalyze is an R package for retrieving and performing exploratory analysis of data from HPA. HPAanalyze provides functionality for importing data tables and xml files from HPA, exporting and visualizing data, as well as downloading all staining images of interest. The package is free, open source, and available via Bioconductor and GitHub. We provide examples of the use of HPAanalyze to investigate proteins altered in the deadly brain tumor glioblastoma. For example, we confirm Epidermal Growth Factor Receptor elevation and Phosphatase and Tensin Homolog loss and suggest the importance of the GTP Cyclohydrolase I/Tetrahydrobiopterin pathway. Additionally, we provide an interactive website for non-programmers to explore and visualize data without the use of R.

Conclusions
HPAanalyze integrates into the R workflow with the tidyverse framework, and it can be used in combination with Bioconductor packages for easy analysis of HPA data.
GhFAD2–3 is required for anther development in Gossypium hirsutum
Authors: Liu Feng , Ma Lihong , Wang Youwu , Li Yanjun , Zhang Xinyu , Xue Fei , Nie Xinhui , Zhu Qianhao , Sun Jie 
Published: September 2019

Abstract

Background
In higher plants, the FAD2 gene encodes the microsomal oleate Δ12-desaturase, one of the key enzymes essential for the biosynthesis of the polyunsaturated lipids that serve many important functions in plant development and stress responses. FAD2 catalyzes the first step, in the biosynthesis of the polyunsaturated fatty acids (PUFAs) found in the cell membrane and cell wall, and it is thus of great importance to investigate the regulatory role of FAD2 in anther development.

Results
We reported the molecular characterization of the cotton (Gossypium hirsutum) GhFAD2 gene family and the essential role of GhFAD2–3 in cotton anther development. G. hirsutum contains four pairs of homoeologous FAD2 genes (GhFAD2–1 to GhFAD2–4). GhFAD2–3 is ubiquitously and relatively highly expressed in all analyzed tissues, particularly in anthers. Specific inhibition of GhFAD2–3 using the RNA interference approach resulted in male sterility due to impaired anther development at the stages from meiosis to maturation. The cellular phenotypic abnormality observed at the meiosis stage of the GhFAD2–3 silenced plant (fad2–3) coincides with the significant reduction of C18:2 in anthers at the same stage. Compared with that of the wild type (WT), the content of C18:1 was 41.48%, which increased by 5 fold in the fad2–3 anther at the pollen maturation stage. Moreover, the ratio of monounsaturated to polyunsaturated fatty acid was 5.43 in fad2–3 anther, which was much higher than that of the WT (only 0.39). Through compositional analysis of anthers cuticle and transcriptome data, we demonstrated it was unfavorable to the development of anther by regulating GhFAD2–3 expression level to increase the oleic acid content.

Conclusions
Our work demonstrated the importance of C18:2 and/or C18:3 in the development of the pollen exine and anther cuticle in cotton and provided clue for further investigation of the physiological significance of the fatty acid composition for plant growth and development.