bluuebunny/crossref_metadata_2025_split huggingface dataset:
GkmExplain: fast and accurate interpretation of nonlinear gapped k-mer SVMs
Authors: Shrikumar Avanti , Prakash Eva , Kundaje Anshul 
Published: May 2019

Abstract

Summary
Support Vector Machines with gapped k-mer kernels (gkm-SVMs) have been used to learn predictive models of regulatory DNA sequence. However, interpreting predictive sequence patterns learned by gkm-SVMs can be challenging. Existing interpretation methods such as deltaSVM, in-silico mutagenesis (ISM) or SHAP either do not scale well or make limiting assumptions about the model that can produce misleading results when the gkm kernel is combined with nonlinear kernels. Here, we propose GkmExplain: a computationally efficient feature attribution method for interpreting predictive sequence patterns from gkm-SVM models that has theoretical connections to the method of Integrated Gradients. Using simulated regulatory DNA sequences, we show that GkmExplain identifies predictive patterns with high accuracy while avoiding pitfalls of deltaSVM and ISM and being orders of magnitude more computationally efficient than SHAP. By applying GkmExplain and a recently developed motif discovery method called TF-MoDISco to gkm-SVM models trained on in vivo transcription factor (TF) binding data, we recover consolidated, non-redundant TF motifs. Mutation impact scores derived using GkmExplain consistently outperform deltaSVM and ISM at identifying regulatory genetic variants from gkm-SVM models of chromatin accessibility in lymphoblastoid cell-lines.

Availability and implementation
Code and example notebooks to reproduce results are at https://github.com/kundajelab/gkmexplain.

Supplementary information
Supplementary data are available at Bioinformatics online.
Drug repositioning based on bounded nuclear norm regularization
Authors: Yang Mengyun , Luo Huimin , Li Yaohang , Wang Jianxin 
Published: May 2019

Abstract

Motivation
Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, matrix completion algorithms efficiently constructing low-rank drug–disease matrix approximations consistent with known associations can be of immense help in discovering the novel drug–disease associations.

Results
In this article, we propose to use a bounded nuclear norm regularization (BNNR) method to complete the drug–disease matrix under the low-rank assumption. Instead of strictly fitting the known elements, BNNR is designed to tolerate the noisy drug–drug and disease–disease similarities by incorporating a regularization term to balance the approximation error and the rank properties. Moreover, additional constraints are incorporated into BNNR to ensure that all predicted matrix entry values are within the specific interval. BNNR is carried out on an adjacency matrix of a heterogeneous drug–disease network, which integrates the drug–drug, drug–disease and disease–disease networks. It not only makes full use of available drugs, diseases and their association information, but also is capable of dealing with cold start naturally. Our computational results show that BNNR yields higher drug–disease association prediction accuracy than the current state-of-the-art methods. The most significant gain is in prediction precision measured as the fraction of the positive predictions that are truly positive, which is particularly useful in drug design practice. Cases studies also confirm the accuracy and reliability of BNNR.

Availability and implementation
The code of BNNR is freely available at https://github.com/BioinformaticsCSU/BNNR.

Supplementary information
Supplementary data are available at Bioinformatics online.
Weighted elastic net for unsupervised domain adaptation with application to age prediction from DNA methylation data
Authors: Handl Lisa , Jalali Adrin , Scherer Michael , Eggeling Ralf , Pfeifer Nico 
Published: May 2019

AbstractMotivationPredictive models are a powerful tool for solving complex problems in computational biology. They are typically designed to predict or classify data coming from the same unknown distribution as the training data. In many real-world settings, however, uncontrolled biological or technical factors can lead to a distribution mismatch between datasets acquired at different times, causing model performance to deteriorate on new data. A common additional obstacle in computational biology is scarce data with many more features than samples. To address these problems, we propose a method for unsupervised domain adaptation that is based on a weighted elastic net. The key idea of our approach is to compare dependencies between inputs in training and test data and to increase the cost of differently behaving features in the elastic net regularization term. In doing so, we encourage the model to assign a higher importance to features that are robust and behave similarly across domains.ResultsWe evaluate our method both on simulated data with varying degrees of distribution mismatch and on real data, considering the problem of age prediction based on DNA methylation data across multiple tissues. Compared with a non-adaptive standard model, our approach substantially reduces errors on samples with a mismatched distribution. On real data, we achieve far lower errors on cerebellum samples, a tissue which is not part of the training data and poorly predicted by standard models. Our results demonstrate that unsupervised domain adaptation is possible for applications in computational biology, even with many more features than samples.Availability and implementationSource code is available at https://github.com/PfeiferLabTue/wenda.Supplementary informationSupplementary data are available at Bioinformatics online.
Cram-JS: reference-based decompression in node and the browser
Authors: Buels Robert , Dider Shihab , Diesh Colin , Robinson James , Holmes Ian 
Published: May 2019

Abstract

Motivation
The CRAM format addresses rising DNA storage costs for short-read sequencing by aligning reads to a reference genome and encoding the resulting alignment with Huffman, subexponential, Elias gamma, rANS, gzip and other codes. The CRAM codec is complex, and until now, there has been no JavaScript implementation.

Results
We have developed a JavaScript library, Cram-JS, that natively reads and decompresses the CRAM format on-the-fly. The library is used in the JBrowse and IGV-JS genome browsers and can readily be used by other JavaScript applications, in the web browser or in Node.

Availability and implementation
Cram-JS is written to the ES-6 standard and is available from the GitHub repository at https://github.com/GMOD/cram-js.
Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis— A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN
Authors: Krauthammer Alex , Tzivinikos Christos , Assa Amit , Miele Erasmo , Strisciuglio Caterina , Urlep Darja , Serban Elena Daniela , Singh Avantika , Winter Harland S , Russell Richard K , Hojsak Iva , Malham Mikkel , Navas-López Víctor Manuel , Croft Nicholas M , Lee Huey Miin , Ledder Oren , Shamasneh Ibrahim , Hussey Seamus , Huynh Hien Q , Wine Eytan , Shah Neil , Sladek Margaret , de Meij Tim G , Romano Claudio , Dipasquale Valeria , Lionetti Paolo , Afzal Nadeem A , Aloi Marina , Lee Kwangyang , Martín-de-Carpi Javier , Yerushalmy-Feler Anat , Subramanian Sreedhar , Weiss Batia , Shouval Dror S 
Published: May 2019

AbstractBackground and AimAcute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC.MethodsThis retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged &lt;18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point.ResultsOf the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate &gt;70 mm/h, and albumin &lt;2.5 g/dL, were significantly associated with 5-year colectomy risk.ConclusionsHigh colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.
Production under input endogeneity and farm-specific risk aversion: evidence from contract farming and Bayesian method
Authors: Mishra Ashok K , Rezitis Anthony N , Tsionas Mike G 
Published: May 2019

AbstractContract farming (CF) has been offered as a solution to missing markets in developing economies. However, little is known as to how the presence of CF affects production risk, technical efficiency and risk attitudes of the smallholder. This study investigates production risk, technical efficiency, output price uncertainty and risk attitudes of contract and independent farmers. Using a Bayesian estimation method and farm-level data from Nepal, we find that contract farmers are more risk-averse than the independent farmers. Contract farmers can increase output by reducing the scale more than independent farmers. We find that labour and capital are risk-reducing, while land and other inputs are risk increasing for both contract and independent farmers. Finally, independent growers consistently over-predict output prices.
Does culture affect soil erosion? Empirical evidence from Europe
Authors: Wuepper David 
Published: May 2019

AbstractI investigate whether cultural differences explain why some European regions are more effective in mitigating soil erosion than others. Specifically, I consider environmental preferences and beliefs as well as time preferences. For causal identification, I use a control function approach. The estimates suggest that a 1 standard deviation increase in pro-environmental culture increases erosion mitigation by 2–9 percentage points. This has important implications for research and policy making, which I discuss.
Fibers on the Fly: Multiscale Mechanisms of Fiber Formation in the Capture Slime of Velvet Worms
Authors: Baer Alexander , Schmidt Stephan , Mayer Georg , Harrington Matthew J 
Published: May 2019

Abstract
Many organisms have evolved a capacity to form biopolymeric fibers outside their bodies for functions such as defense, prey capture, attachment, and protection. In particular, the adhesive capture slime of onychophorans (velvet worms) is remarkable for its ability to rapidly form stiff fibers through mechanical drawing. Notably, fibers that are formed ex vivo from extracted slime can be dissolved in water and new fibers can be drawn from the solution, indicating that fiber formation is encoded in the biomolecules that comprise the slime. This review highlights recent findings on the biochemical and physicochemical principles guiding this circular process in the Australian onychophoran Euperipatoides rowelli. A multiscale cross-disciplinary approach utilizing techniques from biology, biochemistry, physical chemistry, and materials science has revealed that the slime is a concentrated emulsion of nanodroplets comprised primarily of proteins, stabilized via electrostatic interactions, possibly in a coacervate phase. Upon mechanical agitation, droplets coalesce, leading to spontaneous self-assembly and fibrillation of proteins—a completely reversible process. Recent investigations highlight the importance of subtle transitions in protein structure and charge balance. These findings have clear relevance for better understanding this adaptive prey capture behavior and providing inspiration toward sustainable polymer processing.
Occupational asthma; the limited role of air-fed respiratory protective equipment
Authors: Ilgaz Aslihan , Moore Vicky C , Robertson Alastair S , Walters Gareth I , Burge P Sherwood 
Published: May 2019

Abstract

Background
Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking.

Aims
To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility.

Methods
All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE.

Results
Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers.

Conclusions
Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed.
Providing ‘the bigger picture’: benefits and feasibility of integrating remote monitoring from smartphones into the electronic health record
Authors: Austin Lynn , Sharp Charlotte A , van der Veer Sabine N , Machin Matthew , Humphreys John , Mellor Peter , McCarthy Jill , Ainsworth John , Sanders Caroline , Dixon William G 
Published: May 2019

Abstract

Objectives
To establish the acceptability and feasibility of collecting daily patient-generated health data (PGHD) using smartphones and integrating PGHD into the electronic health record, using the example of RA.

Methods
The Remote Monitoring of RA smartphone app was co-designed with patients, clinicians and researchers using qualitative semi-structured interviews and focus groups, including selection of question sets for symptoms and disease impact. PGHD were integrated into the electronic health record of one hospital and available in graphical form during consultations. Acceptability and feasibility were assessed with 20 RA patients and two clinicians over 3 months. A qualitative evaluation included semi-structured interviews with patients and clinicians before and after using the app, and audio-recordings of consultations to explore impact on the consultation. PGHD completeness was summarized descriptively, and qualitative data were analysed thematically.

Results
Patients submitted data on a median of 91% days over 3 months. Qualitative analysis generated three themes: RA as an invisible disease; providing the bigger picture of RA; and enabling person-centred consultations. The themes demonstrated that the system helped render patients’ RA more visible by providing the ‘bigger picture’, identifying real-time changes in disease activity and capturing symptoms that would otherwise have been missed. Graphical summaries during consultations enabled a more person-centred approach whereby patients felt better able to participate in consultations and treatment plans.

Conclusion
Remote Monitoring of RA has uniquely integrated daily PGHD from smartphones into the electronic health record. It has delivered proof-of-concept that such integrated remote monitoring systems are feasible and can transform consultations for clinician and patient benefit.
Voice After Exit: Explaining Diaspora Mobilization for the Arab Spring
Authors: Moss Dana M 
Published: May 2019

AbstractResearch demonstrates that diaspora movements play a powerful role in contentious politics and social change in their homelands under a range of conditions. However, few have systematically explained the conditions that facilitate diaspora movements’ “voice” after “exit” across cases or over time. The article addresses this shortcoming by explaining how and to what extent diaspora movements became auxiliary forces for anti-regime rebellions during the Arab Spring. Using data that include 239 original interviews on Libyan, Syrian, and Yemeni mobilization from the US and Great Britain, the analysis finds that only some diaspora groups played a sustained, full-spectrum role in their home-country’s rebellion by broadcasting their allies’ claims, remitting resources homeward, representing the rebellion to external audiences, brokering between parties, and volunteering on the front lines. The article then demonstrates how differences in (1) the rebellion’s needs, (2) geopolitical support, (3) activist resources, and (4) access to the front lines produced variation in auxiliary activism by national group, host-country, and over time. In so doing, the article contributes to theories of transnationalism, social movements, diaspora politics, and cross-border contentious politics more generally.
Aquaculture role in global food security with nutritional value: a review
Authors: Pradeepkiran Jangampalli Adi 
Published: May 2019

Abstract
Food security is the main path to develop the socioeconomic status in any country in the world to defeat malnutrition. The present scenario in an under developed countries are still facing this problem. Hence the human nutrition deficiencies focus on the importance of animal protein in their regular diet. To overcome this problem, fisheries contribute a significant amount of animal protein to the diets of people worldwide. The aquatic animals are the highly nutritious and cheapest protein sources, which serves as a valuable supplement in diets by providing essential vitamins, proteins, micronutrients, and minerals, for the poor people. Aquaculture is playing a vital role in the developing countries in national economic development, and global food supply. Food and agricultural organization (FAO) declared that this aquaculture has the continuous potentiality to create a developmental goals for the country economy and better human welfare.
Tubewell use protects against rotavirus infection during the monsoons in an urban setting
Authors: Martinez Pamela P. , Mahmud Ayesha , Yunus Mohammad , Faruque A.S.G , Ahmed Tahmeed , Pascual Mercedes , Buckee Caroline O. 
Published: May 2019

AbstractRotavirus, a diarrheal pathogen spread via fecal-oral transmission, is typically characterized by a winter incidence peak in most countries. Unlike for cholera and other water-borne infections, the role of environmental and socioeconomic factors on the spatial variation of rotavirus seasonality remains unclear. Here, we analyze their association with rotavirus seasonality, specifically the odds of monsoon cases, across 46 locations from 2001 to 2012 in Dhaka. Drinking water from tubewells, compared to other sources, has a clear protective effect against cases during the monsoon, when flooding and water contamination are more likely. This finding supports a significant environmental component of transmission.
Is asthma associated with exposure to smoke from a coal mine fire?
Authors: Taylor S , Borg B , Gao C , Brown D , Hoy R , Makar A , McCrabb T , Ikin J , Thompson BR , Abramson MJ 
Published: May 2019

AbstractIn 2014, a fire at the Hazelwood open cut coal mine (Victoria, Australia) burned for about 6 weeks. Residents of the adjacent town of Morwell were exposed to high levels of fine particulate matter (PM2.5) during this period. Three and a half years after the event, this study aimed to investigate the long-term impact of short-term exposure to coal mine fire smoke on asthma.A cross-sectional analysis was undertaken on a group of exposed participants with asthma from Morwell (n=165) and a group of unexposed participants with asthma from the control town of Sale (n=64). Town exposure status was determined by modelled PM2.5data for the mine fire period. Respiratory symptoms were assessed with a validated respiratory health questionnaire and symptom severity score. Asthma control was assessed with an asthma control questionnaire. Lung function testing included spirometry, bronchodilator response, and fraction of exhaled nitric oxide.There was no evidence that exposed Morwell participants had more severe asthma symptoms, worse lung function, or more eosinophilic airway inflammation compared to unexposed Sale participants. However there was some evidence that Morwell participants had more uncontrolled than well-controlled asthma, compared to the participants from Sale (adjusted relative risk ratio 2.71 95%CI: 1.02, 7.21, p=0.046).Three and a half years after exposure, coal mine fire smoke does not appear to be associated with more severe asthma symptoms or worse lung function, but may be associated with poorer asthma control.Summary take home messageIn people with asthma, short-term coal mine fire smoke exposure does not appear to have long-term impact on severity of asthma symptoms, lung function or eosinophilic airway inflammation, but may affect asthma control.
Bioorthogonal protein-DNA conjugation methods for force spectroscopy
Authors: Synakewicz Marie , Bauer Daniela , Rief Matthias , Itzhaki Laura S. 
Published: May 2019

ABSTRACTAccurate and stable site-specific attachment of DNA molecules to proteins is a requirement for many single-molecule force spectroscopy techniques. The most commonly used method still relies on maleimide chemistry involving cysteine residues in the protein of interest. Studies have consequently often focused on model proteins that either have no cysteines or with a small number of cysteines that can be deleted so that cysteines can then be introduced at specific sites. However, many proteins, especially in eukaryotes, contain too many cysteine residues to be amenable to this strategy, and therefore there is tremendous need for new and broadly applicable approaches to site-specific conjugation. Here we present bioorthogonal approaches for making DNA-protein conjugates required in force spectroscopy experiments. Unnatural amino acids are introduced site-specifically and conjugated to DNA oligos bearing the respective modifications to undergo either strain-promoted azide-alkyne cycloaddition (SPAAC) or inverse-electron-demand Diels-Alder (IE-DA) reactions. We furthermore show that SPAAC is compatible with a previously published peptide-based attachment approach. By expanding the available toolkit to tag-free methods based on bioorthogonal reactions, we hope to enable researchers to interrogate the mechanics of a much broader range of proteins than is currently possible.