bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Statistical Curriculum Within Randomized Controlled Trials in Critical Illness*
Authors: McCullough James P. A. , Lipman Jeffrey , Presneill Jeffrey J. 
Published: August 2018

Objectives:
Incomplete biostatistical knowledge among clinicians is widely described. This study aimed to categorize and summarize the statistical methodology within recent critical care randomized controlled trials.

Design:
Descriptive analysis, with comparison of findings to previous work.

Setting:
Ten high-impact clinical journals publishing trials in critical illness.

Subjects:
Randomized controlled trials published between 2011 and 2015 inclusive.

Interventions:
Data extraction from published reports.

Measurements and Main Results:
The frequency and overall proportion of each statistical method encountered, grouped according to those used to generate each trial’s primary outcome and separately according to underlying statistical methodology. Subsequent analysis compared these proportions with previously published reports. A total of 580 statistical tests or methods were identified within 116 original randomized controlled trials published between 2011 and 2015. Overall, the chi-square test was the most commonly encountered (70/116; 60%), followed by the Cox proportional hazards model (63/116; 54%) and logistic regression (53/116; 46%). When classified according to underlying statistical assumptions, the most common types of analyses were tests of 2 × 2 contingency tables and nonparametric tests of rank order. A greater proportion of more complex methodology was observed compared with trial reports from previous work.

Conclusions:
Physicians assessing recent randomized controlled trials in critical illness encounter results derived from a substantial and potentially expanding range of biostatistical methods. In-depth training in the assumptions and limitations of these current and emerging biostatistical methods may not be practically achievable for most clinicians, making accessible specialist biostatistical support an asset to evidence-based clinical practice.
American Football Players in Preseason Training at Risk of Acute Kidney Injury Without Signs of Rhabdomyolysis
Authors: Divine Jon G. , Clark Joseph F. , Colosimo Angelo J. , Detherage John P. , Donaworth Michael A. , Hasselfeld Kimberly A. , Himmler Aaron , Rauch Joseph T. , Mangine Robert E. 
Published: August 2018

Objective:
This study was designed to identify changes in blood biomarkers that would indicate excessive muscle breakdown during the initial 10 days of preseason training in collegiate American football players and subsequently increase their risk of acute kidney injury (AKI).

Design:
Prospective cohort study.

Setting:
Preseason, heat acclimatization period.

Participants:
Twenty-five Division I American football players.

Intervention:
Clinical biomarkers for muscle damage were measured during a preseason training camp. Samples were obtained before camp and approximately 5 and 10 days into camp after completion of heat acclimatization training.

Main Outcomes:
Creatine kinase, myoglobin, lactate dehydrogenase, and creatinine were measured. Glomerular filtration rate (GFR) was calculated. Urine was collected at each blood draw to qualitatively identify hematuria and red blood cells.

Results:
A high percentage of athletes had an asymptomatic reduction in kidney function over the 10-day period. Ten of 23 athletes did have a significant, 31.6%, mean reduction in GFR, placing each at risk of AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification. The plasma myoglobin for the at risk of AKI group had a mean value 8× above their baseline mean on day 5 and statistically significant mean 13× higher on day 10 than baseline. The not at risk of AKI group did not have significant differences between days 0, 5, and 10.

Conclusions:
A relatively high percentage of athletes had an asymptomatic reduction in kidney function during the intense preseason training period. 43.4% of athletes in this study had a significant 31.6% mean reduction in GFR over the 10 days. According to RIFLE classification, this placed each athlete “at risk” of AKI.
Does Weekend Hospital Admission Affect Upper Gastrointestinal Hemorrhage Outcomes?
Authors: Liu Lina , Hao Dongxia , Liu Wei , Wang Lianfu , Wang Xudong 
Published: August 2018

Background:
Compared with weekday admissions, weekend admissions are consistently associated with worse patient outcomes, known as the “weekend effect.” The weekend effect may have adverse health consequences, including death. To determine the potential impact of the weekend effect on primary (ie, mortality) and secondary outcomes of patients with upper gastrointestinal hemorrhage (UGIH).

Materials and Methods:
This was a network meta-analysis based on cohort studies. Databases were searched for studies published up to April 2018. The predefined primary outcome was mortality (30-d mortality and in-hospital mortality). The secondary efficacy outcomes were rebleeding rates, use of endoscopic therapy, need for surgery or angiography, mean length of hospital stay, and time to endoscopy. The study protocol was registered with PROSPERO (No. CRD42018094660).

Results:
In total, 25 studies, including 28 analyses (N=1,203,202 patients), were eligible. The results revealed a tendency toward increased 30-day mortality and increased in-hospital mortality among weekend admissions. In a subgroup analysis, there were significance differences in mortality according to the study location (ie, Europe) and UGIH type (ie, variceal UGIH), with these subgroups having elevated mortality rates. Moreover, weekday admissions were associated with a significant decrease in rebleeding rates. In the network meta-analysis, the study location (in Europe or Asia) and type of UGIH (ie, variceal UGIH) were associated with an increased likelihood of high in-hospital mortality among weekend admissions.

Conclusions:
The evidence derived from this network meta-analysis supports the idea that weekend admissions are associated with an increased risk of death, especially among variceal UGIH patients in European hospitals.
Caring for survivors of childhood cancer: it takes a village
Authors: Song Ailin , Fish Jonathan D. 
Published: August 2018

Purpose of reviewOver 80% of children diagnosed with cancer are now cured. The burgeoning population of survivors of childhood cancer experiences high rates of morbidity and mortality due to ‘late-effects’ of treatment. These can be defined as any consequence of treatment that persists beyond or develops after the completion of cancer therapy. Awareness of late-effects is critically important for pediatricians and adult providers alike, as late-effects impact children in proximity to cancer treatment, as well as adults many decades removed. This review presents the importance of lifelong follow-up care for survivors, highlights existing screening guidelines, and reviews various models of survivor care.Recent findingsNational and international guidelines have been developed to standardize screening for survivors, and multiple models of survivorship care exist. The optimal model likely depends on individual factors, including the survivor's needs and preferences, as well as local resources. Key strategies for the successful care of survivors include accurate risk-stratification for specific late-effects, individualized screening plans, education of survivors and professionals, clear communication between providers, and well coordinated transition of care across services.SummaryEarly identification and management of late-effects are important for survivors of childhood cancer. Providers should be familiar with the risks for specific late-effects and have access to screening guidelines. The strengths and weaknesses of care models, along with individual circumstances, should be considered in designing the optimal approach to care for each survivor.
K-mer based classifiers extract functionally relevant features to support accurate Peroxiredoxin subgroup distinction
Authors: Xiao Jiajie , Turkett William H. 
Published: August 2018

AbstractBackgroundThe Peroxiredoxins (Prx) are a family of proteins that play a major role in antioxidant defense and peroxide-regulated signaling. Six distinct Prx subgroups have been defined based on analysis of structure and sequence regions in proximity to the Prx active site. Analysis of other sequence regions of these annotated proteins may improve the ability to distinguish subgroups and uncover additional representative sequence regions beyond the active site.ResultsThe space of Prx subgroup classifiers is surveyed to highlight similarities and differences in the available approaches. Exploiting the recent growth in annotated Prx proteins, a whole sequence-based classifier is presented that employs support vector machines and a k-mer (k=3) sequence representation.Distinguishing k-mers are extracted and located relative to published active site regions.ConclusionsThis work demonstrates that the 3-mer based classifier can attain high accuracy in subgroup annotation, at rates similar to the current state-of-the-art. Analysis of the classifier’s automatically derived models show that the classification decision is based on a combination of conserved features, including a significant number of residue regions that have not been previously suggested as informative by other classifiers but for which there is evidence of functional relevance.
Nuclear TARBP2 drives oncogenic dysregulation of RNA splicing and decay
Authors: Fish Lisa , Nguyen Hoang C.B. , Zhang Steven , Hochman Myles , Dill Brian D. , Molina Henrik , Najafabadi Hamed S. , Alarcon Claudio , Goodarzi Hani 
Published: August 2018

SUMMARYPost-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the double-stranded RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m6A RNA methylation machinery to its target transcripts, where deposition of m6A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a functional role for this TARBP2 pathway in lung cancer. Using xenograft mouse models, we find that TARBP2 impacts tumor growth in the lung, and that this function is dependent on TARBP2-mediated destabilization of ABCA3 and FOXN3. Finally, we establish the transcription factor ZNF143 as an upstream regulator of TARBP2 expression.RESEARCH HIGHLIGHTSThe RNA-binding protein TARBP2 controls the stability of its target transcripts in the nucleusNuclear TARBP2 recruits the methyltransferase complex to deposit m6A marks on its target transcriptsTARBP2 and m6A-mediated interactions with splicing and nuclear RNA surveillance complexes result in target transcript intron retention and decay.Increased TARBP2 expression is associated with lung cancer and promotes lung cancer growthin vivo.The transcription factor ZNF143 drives oncogenic TARBP2 upregulation in lung cancer.
Unified single-cell analysis of testis gene regulation and pathology in 5 mouse strains
Authors: Jung Min , Wells Daniel , Rusch Jannette , Ahmed Suhaira , Marchini Jonathan , Myers Simon , Conrad Donald F. 
Published: August 2018

AbstractBy removing the confounding factor of cellular heterogeneity, single cell genomics can revolutionize the study of development and disease, but methods are needed to simplify comparison among individuals. To develop such a framework, we assayed the transcriptome in 62,600 single cells from the testes of wildtype mice, and mice with gonadal defects due to disruption of the genes Mlh3, Hormad1, Cul4a or Cnp. The resulting expression atlas of distinct cell clusters revealed novel markers and new insights into testis gene regulation. By jointly analysing mutant and wildtype cells using a model-based factor analysis method, SDA, we decomposed our data into 46 components that identify novel meiotic gene regulatory programmes, mutant-specific pathological processes, and technical effects. Moreover, we identify, de novo, DNA sequence motifs associated with each component, and show that SDA can be used to impute expression values from single cell data. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3-/- and Hormad1-/- testes, an area typically associated with immune privilege. We provide a web application to enable interactive exploration of testis gene expression and components at http://www.stats.ox.ac.uk/~wells/testisAtlas.html
Deep convolutional neural networks for accurate somatic mutation detection
Authors: Sahraeian Sayed Mohammad Ebrahim , Liu Ruolin , Lau Bayo , Mohiyuddin Marghoob , Lam Hugo Y.K. 
Published: August 2018

AbstractWe present NeuSomatic, the first convolutional neural network approach for somatic mutation detection, which significantly outperforms previous methods on different sequencing platforms, sequencing strategies, and tumor purities. NeuSomatic summarizes sequence alignments into small matrices and incorporates more than a hundred features to capture mutation signals effectively. It can be used universally as a stand-alone somatic mutation detection method or with an ensemble of existing methods to achieve the highest accuracy.
Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic forms of autism in post-mortem human brain tissue
Authors: Wong Chloe C.Y. , Smith Rebecca G. , Hannon Eilis , Ramaswami Gokul , Parikshak Neelroop N. , Assary Elham , Troakes Claire , Poschmann Jeremie , Schalkwyk Leonard C. , Sun Wenjie , Prabhakar Shyam , Geschwind Daniel H. , Mill Jonathan 
Published: August 2018

AbstractAutism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behavior. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular etiology of ASD, we quantified genome-wide patterns of DNA methylation in 233 post-mortem tissues samples isolated from three brain regions (prefrontal cortex, temporal cortex and cerebellum) dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the cerebellum. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically-defined subtype of ASD, were characterized by striking differences in DNA methylation across a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.
Characterization of osteoarthritis phenotypes by global metabolomic profiling of human synovial fluid
Authors: Carlson Alyssa K. , Rawle Rachel A. , Wallace Cameron W. , Brooks Ellen G. , Adams Erik , Greenwood Mark C. , Olmer Merissa , Lotz Martin K. , Bothner Brian , June Ronald K. 
Published: August 2018

AbstractObjectiveOsteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolic phenotypes of OA from human synovial fluid.DesignPost mortemsynovial fluids (n=75) were analyzed by high performance-liquid chromatography mass spectrometry (HPLC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression.ResultsGlobal metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Phenotypes of OA exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid.ConclusionThese results revealed distinct metabolic phenotypes of OA in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers and assist in developing personalized interventions for subgroups of OA patients.
The role of familial socio-political forces on new venture creation in family business
Authors: Bhatnagar Navneet , Ramachandran Kavil , Ray Sougata 
Published: August 2018

PurposeNew venture (NV) creation is critical to the growth and long-term survival of business groups. The purpose of this paper is to investigate the NV creation process in family business (FB) context and examine the influence of familial socio-political considerations and dynamics on venture creation processes.Design/methodology/approachThe paper employs a triangulation technique drawing from the extant literature, observations from 25 in-depth interviews of FB leaders and insights from two FB practitioners and abductive reasoning to theorize on the NV creation process and the influence of socio-political considerations and dynamics within family.FindingsThe results show that there are four distinct stages of the NV creation process in FB context. Familial socio-political considerations and dynamics greatly influence the NV creation process. These considerations and dynamics vary according to the socio-political clout enjoyed by the proposer. Leadership’s predisposition to the proposer and the proposer’s socio-political clout in the family determine whether an NV proposal leads to venture creation.Research limitations/implicationsThe study extends NV creation literature by suggesting that in addition to the economic rationale, socio-political considerations play a critical role in venture creation decisions. Future research can validate the findings with quantitative analysis.Practical implicationsFB members must garner strong socio-political support for their NV proposal. FB leaders must ensure that their NV proposal evaluation and resource allocation decisions are not unduly influenced by the proposer’s socio-political clout.Originality/valueThe study views the NV creation process in FB context from the lens of familial forces at play. It identifies four distinct stages of the NV creation process and examines the role played by familial socio-political considerations and dynamics during each stage.
Embedded order reduction of hierarchical systems within an mCCM framework
Authors: Popp Michael , Mathis Wolfgang 
Published: August 2018

Purpose
The purpose of this paper is to present the embedding of linear and nonlinear order reduction methods in a theoretical framework for handling hierarchically interconnected dynamical systems.

Design/methodology/approach
Based on the component connection modeling (CCM), a modified framework called mCCM for describing interconnected dynamic systems especially with hierarchical structures is introduced and used for order reduction purposes. The balanced truncation method for linear systems and the trajectory piecewise linear reduction scheme are used for the order reduction of systems described within the mCCM framework.

Findings
It is shown that order reduction methods can be embedded into the context of interconnected dynamical systems with the benefit of having a further degree of freedom in form of the hierarchical level, on which the order reduction is performed.

Originality/value
The aspect of hierarchy within system descriptions is exploited for order reduction purposes. This distinguishes the presented approach from common methods, which already start with single large-scale systems without explicitly considering hierarchical structures.
Global dynamics of immigrant entrepreneurship
Authors: Nazareno Jennifer , Zhou Min , You Tianlong 
Published: August 2018

PurposeThe purpose of this paper is to review the existing literature on immigrant entrepreneurship since the mid-2000s to examine the changing trends, variations and theoretical advances in immigrant entrepreneurship in Western societies.Design/methodology/approachUsing the SocIndex and Proquest Business Premium databases, the authors conducted a literature review of about 100 peer-reviewed articles published since the mid-2000s. The authors critically assess the main research findings, identify key concepts and models that have been developed over the past decade, and offer new theoretical insight into the ever-changing global dynamics of immigrant entrepreneurship. Although the focus is on the USA, the authors also include some seminal research based in other Western countries of immigrant reception.FindingsBased on a critical review of existing research that has been published between 2004 and the present, the authors highlight main trends and variations of the entrepreneurial endeavors among diasporic migrants, address the emerging forces shaping immigrant entrepreneurship, highlight theoretical advances in the field of entrepreneurship studies, and suggest new directions for future research. The authors note that the changing trends and ethnonational variations are caused not only by unequal access to human capital, social capital, financial capital, and cross-border venture capital on the part of individual entrepreneurs, but also by differences in broader structural circumstances in the home country and/or host country and interaction between national/local and transnational/global forces. The authors discuss new theoretical advances, identify gaps and raise questions for future research.Originality/valueThe review offers important insight into the ever-changing local and global dynamics of immigrant entrepreneurship and broadens the established conceptual and theoretical models in the sociology of immigrant/ethnic entrepreneurship.