bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation
Authors: Xu Ran , Xu Yixi , Huo Wei , Lv Zhicong , Yuan Jingsong , Ning Shaokai , Wang Qingsong , Hou Mei , Gao Ge , Ji Jianguo , Chen Junjie , Guo Rong , Xu Dongyi 
Published: October 2018

Significance
The Mre11–Rad50–Nbs1 (MRN) complex is well known for participating in DNA damage response pathways and mediating the ATM-dependent phosphorylation signaling cascade. Hypomorphic mutations in the human MRN complex have been identified in autosomal recessive genetic diseases, ataxia-telangiectasia–like disorder, and Nijmegen breakage syndrome. Here, we show that MRN forms a mitosis-specific complex with a protein, MMAP, which mediates a mitotic signaling cascade between PLK1 and KIF2A. We demonstrate that the assembly of this complex is crucial for normal spindle dynamics during mitosis. Thus, our study describes a signaling cascade in which PLK1-dependent phosphorylation promotes the assembly of the MRN–MMAP–PLK1–KIF2A complex, leading to mitotic spindle turnover and chromosome alignment.
Swi5–Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51 dissociation
Authors: Lu Chih-Hao , Yeh Hsin-Yi , Su Guan-Chin , Ito Kentaro , Kurokawa Yumiko , Iwasaki Hiroshi , Chi Peter , Li Hung-Wen 
Published: October 2018

Significance
In DNA homologous recombination, recombinase-coated single-stranded DNA filament formation is the first committed step and is subject to tight regulation. Stabilization of nucleoprotein filament by accessory proteins can be achieved by enhancing filament formation, reducing filament disassembly, or both. However, the mechanism of regulation is not understood by conventional biochemical methods. This is a study of the mechanism of how accessory proteins stimulate filament assembly by applying single-molecule methods that allow us to monitor the binding of Rad51 on DNA in mouse and fission yeast. Our results show that the Swi5–Sfr1 complex demonstrates the evolutionarily conserved stimulation of Rad51 filament assembly by stabilizing Rad51 on DNA, allowing both the formation of the stable nucleus and the reduction of Rad51 dissociation.
Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations
Authors: Rivas-Carrillo Salvador Daniel , Pettersson Mats E. , Rubin Carl-Johan , Jern Patric 
Published: October 2018

Significance
Retroviruses have invaded vertebrate hosts during millions of years by occasional germline infections, which were transmitted to the host offspring through generations as inherited endogenous retroviruses (ERVs). Thus, ERVs provide a remarkable record of virus–host interactions. State-of-the-art sequencing methods facilitate ERV identification to decipher their long-term associations with host species. By expanding the scope beyond presence or absence in a single reference genome assembly, it is possible to estimate ERV frequencies and spread in related wild and domestic host populations. Here we demonstrate a considerable ERV makeup variance in wild and domestic rabbit populations, which offers insights into retrovirus–host coevolution and an extension to common strategies in population comparative genomics.
LION LBD: a literature-based discovery system for cancer biology
Authors: Pyysalo Sampo , Baker Simon , Ali Imran , Haselwimmer Stefan , Shah Tejas , Young Andrew , Guo Yufan , Högberg Johan , Stenius Ulla , Narita Masashi , Korhonen Anna 
Published: October 2018

Abstract

Motivation
The overwhelming size and rapid growth of the biomedical literature make it impossible for scientists to read all studies related to their work, potentially leading to missed connections and wasted time and resources. Literature-based discovery (LBD) aims to alleviate these issues by identifying implicit links between disjoint parts of the literature. While LBD has been studied in depth since its introduction three decades ago, there has been limited work making use of recent advances in biomedical text processing methods in LBD.

Results
We present LION LBD, a literature-based discovery system that enables researchers to navigate published information and supports hypothesis generation and testing. The system is built with a particular focus on the molecular biology of cancer using state-of-the-art machine learning and natural language processing methods, including named entity recognition and grounding to domain ontologies covering a wide range of entity types and a novel approach to detecting references to the hallmarks of cancer in text. LION LBD implements a broad selection of co-occurrence based metrics for analyzing the strength of entity associations, and its design allows real-time search to discover indirect associations between entities in a database of tens of millions of publications while preserving the ability of users to explore each mention in its original context in the literature. Evaluations of the system demonstrate its ability to identify undiscovered links and rank relevant concepts highly among potential connections.

Availability and implementation
The LION LBD system is available via a web-based user interface and a programmable API, and all components of the system are made available under open licenses from the project home page http://lbd.lionproject.net.

Supplementary information
Supplementary data are available at Bioinformatics online.
Pisces: an accurate and versatile variant caller for somatic and germline next-generation sequencing data
Authors: Dunn Tamsen , Berry Gwenn , Emig-Agius Dorothea , Jiang Yu , Lei Serena , Iyer Anita , Udar Nitin , Chuang Han-Yu , Hegarty Jeff , Dickover Michael , Klotzle Brandy , Robbins Justin , Bibikova Marina , Peeters Marc , Strömberg Michael 
Published: October 2018

Abstract

Motivation
Next-generation sequencing technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants.

Results
We have developed Pisces, a rapid, versatile and accurate small-variant calling suite designed for somatic and germline amplicon sequencing applications. Accuracy is achieved by four distinct modules, each incorporating a number of novel algorithmic strategies.

Availability and implementation
Pisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces. Pisces is available on the BaseSpace™ SequenceHub. It is distributed on Illumina sequencing platforms such as the MiSeq™ and is included in the Praxis™ Extended RAS Panel test which was recently approved by the FDA.

Supplementary information
Supplementary data are available at Bioinformatics online.
TEPIC 2—an extended framework for transcription factor binding prediction and integrative epigenomic analysis
Authors: Schmidt Florian , Kern Fabian , Ebert Peter , Baumgarten Nina , Schulz Marcel H 
Published: October 2018

Abstract

Summary
Prediction of transcription factor (TF) binding from epigenetics data and integrative analysis thereof are challenging. Here, we present TEPIC 2 a framework allowing for fast, accurate and versatile prediction, and analysis of TF binding from epigenetics data: it supports 30 species with binding motifs, computes TF gene and scores up to two orders of magnitude faster than before due to improved implementation, and offers easy-to-use machine learning pipelines for integrated analysis of TF binding predictions with gene expression data allowing the identification of important TFs.

Availability and implementation
TEPIC is implemented in C++, R, and Python. It is freely available at https://github.com/SchulzLab/TEPIC and can be used on Linux based systems.

Supplementary information
Supplementary data are available at Bioinformatics online.
The role of intangible assets in explaining the investment–profit puzzle
Authors: Orhangazi Özgür 
Published: October 2018

AbstractStarting around the early 2000s, and especially after the 2008 crisis, the rate of capital accumulation for US nonfinancial corporations has slowed down despite relatively high profitability; indicating a weakening of the link between profitability and investment. While the literature mostly focuses on financialisation and globalisation as the reasons behind this slowdown, I suggest adding another layer to these explanations and argue that, in conjunction with financialisation and globalisation, we need to pay attention to the increased use of intangible assets by nonfinancial corporations in the last two decades. Intangibles such as brand names, trademarks, patents and copyrights play a role in the widening of the profit–investment gap as the use of these assets enables firms to increase market power and profitability without necessarily generating a corresponding increase in fixed capital investment. After discussing the ways nonfinancial corporations use intangible assets, I look at large corporations in the USA and find the following: (i) The ratio of intangible assets to the capital stock increased in general. This increase is highest for firms in high-technology, healthcare, nondurables and telecommunications. (ii) Industries with higher intangible asset ratios have lower investment to profit ratios. (iii) Industries with higher intangible asset ratios have higher markups and profitability. (iv) The composition of the nonfinancial corporate sector has changed and the weight of high-technology and healthcare firms has increased; but this increase did not correspond to an equal increase in their investment share. The decline in the investment share of durables, nondurables and machinery is matched by an increase in the investment share of location-specific industries with low intangible asset use, most notably firms in energy extraction. In general, these firms have steadier markups and higher investment to profit ratios. (v) Yet, intangible-intensive industries’ profitability has increased faster than their share of investment or total assets. All in all, these findings are in line with the suggestion that the increased use of intangible assets enables firms to have high profitability without a corresponding increase in investment.
Temporal trends in adoption and outcomes of transcatheter aortic valve implantation: a SwissTAVI Registry analysis
Authors: Stortecky Stefan , Franzone Anna , Heg Dik , Tueller David , Noble Stephane , Pilgrim Thomas , Jeger Raban , Toggweiler Stefan , Ferrari Enrico , Nietlispach Fabian , Taramasso Maurizio , Maisano Francesco , Grünenfelder Jürg , Muller Olivier , Huber Christoph , Roffi Marco , Carrel Thierry , Wenaweser Peter , Windecker Stephan 
Published: October 2018

Abstract

Aims
To describe temporal trends in adoption and performance of transcatheter aortic valve implantation (TAVI) in Switzerland over a period of 5 years.

Methods and results
Between 2011 and 2015, a total of 3493 patients were consecutively included in the SwissTAVI Registry (NCT01368250) and analysed for the purpose of this study. The primary outcome measure was all-cause mortality at 1 year after TAVI. Over the 5-year period, a six-fold increase in the number of procedures was observed, whereas the baseline surgical risk estimated by the Society of Thoracic Surgeon (STS) score declined (from 6.8 ± 4.4% to 4.6 ± 3.6, P < 0.001). Overall, 1-year mortality amounted to 12.8%; mortality was highest in the first annual cohorts (14.6%, 14.8%, and 15.9% in 2011, 2012, and 2013, respectively) and decreased to 13.4% in 2014 and 9.7% in 2015. While rates of cerebrovascular events, peri-procedural myocardial infarction, moderate/severe paravalvular regurgitation, and Stage 3 acute kidney injury did not significantly change over time, a significant reduction in life threatening or major bleeding was noted at 30-day follow-up during the latest compared with earlier years of recruitment.

Conclusion
This long-term recruitment analysis of a national TAVI registry showed rapid adoption paralleled by a progressive decrease of patients’ baseline risk profile. Early and late survival significantly improved over time as did the rate of life threatening or major bleeding.
Infant nutrition and growth: trends and inequalities in four population-based birth cohorts in Pelotas, Brazil, 1982–2015
Authors: Gonçalves Helen , Barros Fernando C , Buffarini Romina , Horta Bernardo L , Menezes Ana M B , Barros Aluísio J D , Domingues Marlos R , Victora Cesar G ,   Pelotas Cohorts Study Group, Matijasevich Alicia , Bertoldi Andrea Dãmaso , Bassani Diego G , Wehrmeister Fernando C , Santos Iná S , Murray Joseph , Tovo-Rodrigues Luciana , Assunção Maria Cecilia F , Silveira Mariangela F , Hallal Pedro R C 
Published: October 2018

Abstract

Background
Levels of child undernutrition have declined in many middle-income countries, whereas overweight and obesity have increased. We describe time trends in nutritional indicators at age 1 year in the 1982, 1993, 2004 and 2015 Pelotas (Brazil) Birth Cohorts.

Methods
Each study included all children born in the urban area of the city, with over 4 200 births in each cohort. Children were measured at approximately 12 months of age. Anthropometric indicators were calculated according to World Health Organization Growth Standards. Stunting and wasting were defined as &lt;-2 Z scores for length for age and weight for length, and overweight as &gt;2 Z scores for weight for length. Prevalence was stratified by sex, maternal skin colour and family income.

Results
The prevalence of stunting declined by 53% (from 8.3% to 3.9%) from 1982 to 2015. Wasting prevalence remained stable at low levels (1.8% in 1982 and 1.7% in 2015), whereas overweight increased by 88% (6.5% to 12.2%). Undernutrition was more common among boys, those born to mothers with brown or black skin colour and in the poorest quintile of families. Socioeconomic inequalities in undernutrition decreased markedly over time. Overweight was markedly more common among the rich in 1982, but fast increase among the poor eliminated socioeconomic differences by 2015, when all groups showed similar prevalence.

Conclusions
Our results confirm the rapid nutrition transition in Brazil, with marked reduction in levels and inequalities in undernutrition in parallel with a rapid increase in overweight, which became the main nutritional problem for children.
Cranky comments: detecting clinical decision support malfunctions through free-text override reasons
Authors: Aaron Skye , McEvoy Dustin S , Ray Soumi , Hickman Thu-Trang T , Wright Adam 
Published: October 2018

AbstractBackgroundRule-base clinical decision support alerts are known to malfunction, but tools for discovering malfunctions are limited.ObjectiveInvestigate whether user override comments can be used to discover malfunctions.MethodsWe manually classified all rules in our database with at least 10 override comments into 3 categories based on a sample of override comments: “broken,” “not broken, but could be improved,” and “not broken.” We used 3 methods (frequency of comments, cranky word list heuristic, and a Naïve Bayes classifier trained on a sample of comments) to automatically rank rules based on features of their override comments. We evaluated each ranking using the manual classification as truth.ResultsOf the rules investigated, 62 were broken, 13 could be improved, and the remaining 45 were not broken. Frequency of comments performed worse than a random ranking, with precision at 20 of 8 and AUC = 0.487. The cranky comments heuristic performed better with precision at 20 of 16 and AUC = 0.723. The Naïve Bayes classifier had precision at 20 of 17 and AUC = 0.738.DiscussionOverride comments uncovered malfunctions in 26% of all rules active in our system. This is a lower bound on total malfunctions and much higher than expected. Even for low-resource organizations, reviewing comments identified by the cranky word list heuristic may be an effective and feasible way of finding broken alerts.ConclusionOverride comments are a rich data source for finding alerts that are broken or could be improved. If possible, we recommend monitoring all override comments on a regular basis.
Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol
Authors: Evenepoel Pieter , Claes Kathleen , Meijers Björn , Laurent Michaël R , Bammens Bert , Naesens Maarten , Sprangers Ben , Cavalier Etienne , Kuypers Dirk 
Published: October 2018

Abstract
The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median −2.2% [interquartile range (IQR) −5.9–1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR −3.2–7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.
Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis
Authors: Coppo Rosanna 
Published: October 2018

AbstractThe search of personalized treatment for a subject with immunoglobulin A nephropathy (IgAN) is appealing since the individual long-term outcome is highly variable in spite of common mild clinical signs such as microscopic haematuria, moderate proteinuria and slightly reduced glomerular filtration rate (GFR). The only risk factor considered by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines to target corticosteroid/immunosuppressive treatment in IgAN is proteinuria persistently >1 g/day despite 3–6 months of optimized supportive care. However, proteinuria in IgAN may result not only from active lesions but also from sclerotic glomerular lesions with hyperfiltration and tubular damage. The Oxford classification study and subsequent investigations have indicated the value of pathology risk factors for progression independent of proteinuria, blood pressure and GFR at renal biopsy. Meanwhile new studies have provided an improved understanding of the pathogenetic mechanisms operating in IgAN leading to kidney tissue damage. These findings suggest the possibility for the individual patient with IgAN of using a pathology-based therapy, taking into consideration the pathogenetic mechanisms operating at the time of renal biopsy. This review is largely opinion based, since evidence-based reports are mostly incomplete: hypotheses are suggested based on interesting published investigations. The clinician faces a daily challenge: find the best management for his/her patient, modelling a rather general indication as obtained by the guidelines to the needs of the patient. This review offers some considerations that hopefully will be useful in this difficult choice.
Neurosurgery and Manned Spaceflight
Authors: Panesar Sandip S , Fernandez-Miranda Juan C , Kliot Michel , Ashkan Keyoumars 
Published: October 2018

ABSTRACT
There has been a renewed interest in manned spaceflight due to endeavors by private and government agencies. Publicized goals include manned trips to or colonization of Mars. These missions will likely be of long duration, exceeding existing records for human exposure to extra-terrestrial conditions. Participants will be exposed to microgravity, temperature extremes, and radiation, all of which may adversely affect their physiology. Moreover, pathological mechanisms may differ from those of a terrestrial nature. Known central nervous system (CNS) changes occurring in space include rises in intracranial pressure and spinal unloading. Intracranial pressure increases are thought to occur due to cephalad re-distribution of body fluids secondary to microgravity exposure. Spinal unloading in microgravity results in potential degenerative changes to the bony vertebrae, intervertebral discs, and supportive musculature. These phenomena are poorly understood. Trauma is of highest concern due to its potential to seriously incapacitate crewmembers and compromise missions. Traumatic pathology may also be exacerbated in the setting of altered CNS physiology. Though there are no documented instances of CNS pathologies arising in space, existing diagnostic and treatment capabilities will be limited relative to those on Earth. In instances where neurosurgical intervention is required in space, it is not known whether open or endoscopic approaches are feasible. It is obvious that prevention of trauma and CNS pathology should be emphasized. Further research into neurosurgical pathology, its diagnosis, and treatment in space are required should exploratory or colonization missions be attempted.
Variability in Emergency Medicine Provider Decisions on Hospital Admission and Antibiotic Treatment in a Survey Study for Acute Bacterial Skin and Skin Structure Infections: Opportunities for Antimicrobial Stewardship Education
Authors: Almarzoky Abuhussain Safa S , Burak Michelle A , Adams Danyel K , Kohman Kelsey N , Tart Serina B , Hobbs Athena L V , Jacknin Gabrielle , Nailor Michael D , Keyloun Katelyn R , Nicolau David P , Kuti Joseph L 
Published: October 2018

Abstract

Background
Acute bacterial skin and skin structure infections (ABSSSIs) are a frequent cause of emergency department (ED) visits. Providers in the ED have many decisions to make during the initial treatment of ABSSSI. There are limited data on the patient factors that influence these provider decisions.

Methods
An anonymous survey was administered to providers at 6 EDs across the United States. The survey presented patient cases with ABSSSIs ≥75 cm2 and escalating clinical scenarios including relapse, controlled diabetes, and sepsis. For each case, participants were queried on their decision for admission vs discharge and antibiotic therapy (intravenous, oral, or both) and to rank the factors that influenced their antibiotic decision.

Results
The survey was completed by 130 providers. For simple ABSSSI, the majority of providers chose an oral antibiotic and discharged patients home. The presence of recurrence or controlled diabetes resulted in more variation in responses. Thirty-four (40%) and 51 (60%) providers chose intravenous followed by oral antibiotics and discharged the recurrence and diabetes cases, respectively. Presentation with sepsis resulted in initiation with intravenous antibiotics (122, 95.3%) and admission (125, 96.1%) in most responses.

Conclusions
Variability in responses to certain patient scenarios suggests opportunities for education of providers in the ED and the development of an ABSSSI clinical pathway to help guide treatment.