bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative trait loci identification for brain endophenotypes via new additive model with random networks
Authors: Wang Xiaoqian , Chen Hong , Yan Jingwen , Nho Kwangsik , Risacher Shannon L , Saykin Andrew J , Shen Li , Huang Heng ,   for the ADNI
Published: July 2018

AbstractMotivationThe identification of quantitative trait loci (QTL) is critical to the study of causal relationships between genetic variations and disease abnormalities. We focus on identifying the QTLs associated to the brain endophenotypes in imaging genomics study for Alzheimer’s Disease (AD). Existing research works mainly depict the association between single nucleotide polymorphisms (SNPs) and the brain endophenotypes via the linear methods, which may introduce high bias due to the simplicity of the models. Since the influence of QTLs on brain endophenotypes is quite complex, it is desired to design the appropriate non-linear models to investigate the associations of genotypes and endophenotypes.ResultsIn this paper, we propose a new additive model to learn the non-linear associations between SNPs and brain endophenotypes in Alzheimer’s disease. Our model can be flexibly employed to explain the non-linear influence of QTLs, thus is more adaptive for the complex distribution of the high-throughput biological data. Meanwhile, as an important computational learning theory contribution, we provide the generalization error analysis for the proposed approach. Unlike most previous theoretical analysis under independent and identically distributed samples assumption, our error bound is based on m-dependent observations, which is more appropriate for the high-throughput and noisy biological data. Experiments on the data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort demonstrate the promising performance of our approach for identifying biological meaningful SNPs.Availability and implementationAn executable is available at https://github.com/littleq1991/additive_FNNRW.
Analysis of single amino acid variations in singlet hot spots of protein–protein interfaces
Authors: Ozdemir E Sila , Gursoy Attila , Keskin Ozlem 
Published: July 2018

Abstract

Motivation
Single amino acid variations (SAVs) in protein–protein interaction (PPI) sites play critical roles in diseases. PPI sites (interfaces) have a small subset of residues called hot spots that contribute significantly to the binding energy, and they may form clusters called hot regions. Singlet hot spots are the single amino acid hot spots outside of the hot regions. The distribution of SAVs on the interface residues may be related to their disease association.

Results
We performed statistical and structural analyses of SAVs with literature curated experimental thermodynamics data, and demonstrated that SAVs which destabilize PPIs are more likely to be found in singlet hot spots rather than hot regions and energetically less important interface residues. In contrast, non-hot spot residues are significantly enriched in neutral SAVs, which do not affect PPI stability. Surprisingly, we observed that singlet hot spots tend to be enriched in disease-causing SAVs, while benign SAVs significantly occur in non-hot spot residues. Our work demonstrates that SAVs in singlet hot spot residues have significant effect on protein stability and function.

Availability and implementation
The dataset used in this paper is available as Supplementary Material. The data can be found at http://prism.ccbb.ku.edu.tr/data/sav/ as well.

Supplementary information
Supplementary data are available at Bioinformatics online.
CisPi: a transcriptomic score for disclosing cis-acting disease-associated lincRNAs
Authors: Wang Zhezhen , Cunningham John M , Yang Xinan H 
Published: July 2018

Abstract

Motivation
Long intergenic noncoding RNAs (lincRNAs) have risen to prominence in cancer biology as new biomarkers of disease. Those lincRNAs transcribed from active cis-regulatory elements (enhancers) have provided mechanistic insight into cis-acting regulation; however, in the absence of an enhancer hallmark, computational prediction of cis-acting transcription of lincRNAs remains challenging. Here, we introduce a novel transcriptomic method: a cis-regulatory lincRNA–gene associating metric, termed ‘CisPi’. CisPi quantifies the mutual information between lincRNAs and local gene expression regarding their response to perturbation, such as disease risk-dependence. To predict risk-dependent lincRNAs in neuroblastoma, an aggressive pediatric cancer, we advance this scoring scheme to measure lincRNAs that represent the minority of reads in RNA-Seq libraries by a novel side-by-side analytical pipeline.

Results
Altered expression of lincRNAs that stratifies tumor risk is an informative readout of oncogenic enhancer activity. Our CisPi metric therefore provides a powerful computational model to identify enhancer-templated RNAs (eRNAs), eRNA-like lincRNAs, or active enhancers that regulate the expression of local genes. First, risk-dependent lincRNAs revealed active enhancers, over-represented neuroblastoma susceptibility loci, and uncovered novel clinical biomarkers. Second, the prioritized lincRNAs were significantly prognostic. Third, the predicted target genes further inherited the prognostic significance of these lincRNAs. In sum, RNA-Seq alone is sufficient to identify disease-associated lincRNAs using our methodologies, allowing broader applications to contexts in which enhancer hallmarks are not available or show limited sensitivity.

Availability and implementation
The source code is available on request. The prioritized lincRNAs and their target genes are in the Supplementary Material.

Supplementary information
Supplementary data are available at Bioinformatics online.
piMGM: incorporating multi-source priors in mixed graphical models for learning disease networks
Authors: Manatakis Dimitris V , Raghu Vineet K , Benos Panayiotis V 
Published: July 2018

AbstractMotivationLearning probabilistic graphs over mixed data is an important way to combine gene expression and clinical disease data. Leveraging the existing, yet imperfect, information in pathway databases for mixed graphical model (MGM) learning is an understudied problem with tremendous potential applications in systems medicine, the problems of which often involve high-dimensional data.ResultsWe present a new method, piMGM, which can learn with accuracy the structure of probabilistic graphs over mixed data by appropriately incorporating priors from multiple experts with different degrees of reliability. We show that piMGM accurately scores the reliability of prior information from a given expert even at low sample sizes. The reliability scores can be used to determine active pathways in healthy and disease samples. We tested piMGM on both simulated and real data from TCGA, and we found that its performance is not affected by unreliable priors. We demonstrate the applicability of piMGM by successfully using prior information to identify pathway components that are important in breast cancer and improve cancer subtype classification.Availability and implementationhttp://www.benoslab.pitt.edu/manatakisECCB2018.htmlSupplementary informationSupplementary data are available at Bioinformatics online.
Starting Young: Trends in Opioid Therapy Among US Adolescents and Young Adults With Inflammatory Bowel Disease in the Truven MarketScan Database Between 2007 and 2015
Authors: Wren Anava A , Bensen Rachel , Sceats Lindsay , Dehghan Melody , Yu Helen , Wong Jessie J , MacIsaac Donna , Sellers Zachary M , Kin Cindy , Park K T 
Published: July 2018

AbstractBackgroundOpioids are commonly prescribed for relief in inflammatory bowel disease (IBD). Emerging evidence suggests that adolescents and young adults are a vulnerable population at particular risk of becoming chronic opioid users and experiencing adverse effects.ObjectivesThis study evaluates trends in the prevalence and persistence of chronic opioid therapy in adolescents and young adults with IBD in the United States.MethodA longitudinal retrospective cohort analysis was conducted with the Truven MarketScan Database from 2007 to 2015. Study subjects were 15–29 years old with ≥2 IBD diagnoses (Crohn’s: 555/K50; ulcerative colitis: 556/K51). Opioid therapy was identified with prescription claims within the Truven therapeutic class 60: opioid agonists. Persistence of opioid use was evaluated by survival analysis for patients who remained in the database for at least 3 years following index chronic opioid therapy use.ResultsIn a cohort containing 93,668 patients, 18.2% received chronic opioid therapy. The annual prevalence of chronic opioid therapy increased from 9.3% in 2007 to 10.8% in 2015 (P < 0.01), peaking at 12.2% in 2011. Opioid prescriptions per patient per year were stable (approximately 5). Post hoc Poisson regression analyses demonstrated that the number of opioid pills dispensed per year increased with age and was higher among males. Among the 2503 patients receiving chronic opioid therapy and followed longitudinally, 30.5% were maintained on chronic opioid therapy for 2 years, and 5.3% for all 4 years.ConclusionSustained chronic opioid use in adolescents and young adults with IBD is increasingly common, underscoring the need for screening and intervention for this vulnerable population.
A Review of Current Standards and the Evolution of Histopathology Nomenclature for Laboratory Animals
Authors: Elmore Susan A , Cardiff Robert , Cesta Mark F , Gkoutos Georgios V , Hoehndorf Robert , Keenan Charlotte M , McKerlie Colin , Schofield Paul N , Sundberg John P , Ward Jerrold M 
Published: July 2018

Abstract
The need for international collaboration in rodent pathology has evolved since the 1970s and was initially driven by the new field of toxicologic pathology. First initiated by the World Health Organization’s International Agency for Research on Cancer for rodents, it has evolved to include pathology of the major species (rats, mice, guinea pigs, nonhuman primates, pigs, dogs, fish, rabbits) used in medical research, safety assessment, and mouse pathology. The collaborative effort today is driven by the needs of the regulatory agencies in multiple countries, and by needs of research involving genetically engineered animals, for “basic” research and for more translational preclinical models of human disease. These efforts led to the establishment of an international rodent pathology nomenclature program. Since that time, multiple collaborations for standardization of laboratory animal pathology nomenclature and diagnostic criteria have been developed, and just a few are described herein. Recently, approaches to a nomenclature that is amenable to sophisticated computation have been made available and implemented for large-scale programs in functional genomics and aging. Most terminologies continue to evolve as the science of human and veterinary pathology continues to develop, but standardization and successful implementation remain critical for scientific communication now as ever in the history of veterinary nosology.
A Trilinear Restriction Estimate for the Hyperbolic Paraboloid with Sharp Dependence on Transversality
Authors: Ponce Vanegas Felipe 
Published: July 2018

Abstract
The problem of restriction in harmonic analysis revolves around the operator $\mathcal{R}:f\mapsto \hat{f}|_{S}$, where $S$ is a manifold in $\mathbb{R}^n$. A fundamental inequality of the multilinear theory of the restriction operator is $\big \lVert{\prod _{k=1}^{n}\mathcal{R}^{*} f_{k}}\big \rVert _{L^{2/(n-1)}(\mathbb{R}^{n})}\le C\prod _{k=1}^{n}\lVert{f_k}\rVert _{L^{2}(S_k)}$, where $\mathcal{R}^{*}$ is the dual operator and the hypersurfaces $S_k$ satisfy a condition of transversality. This estimate was proven by Bennett, Carbery, and Tao, up to logarithmic losses, but without optimal dependence on transversality in the constant $C$. For subsets of the paraboloid in $\mathbb{R}^{3}$, Ramos got the sharp dependence on transversality. In this paper we extend this result to subsets of the hyperbolic paraboloid.
Developing and maintaining clinical decision support using clinical knowledge and machine learning: the case of order sets
Authors: Zhang Yiye , Trepp Richard , Wang Weiguang , Luna Jorge , Vawdrey David K , Tiase Victoria 
Published: July 2018

AbstractDevelopment and maintenance of order sets is a knowledge-intensive task for off-the-shelf machine-learning algorithms alone. We hypothesize that integrating clinical knowledge with machine learning can facilitate effective development and maintenance of order sets while promoting best practices in ordering. To this end, we simulated the revision of an “AM Lab Order Set” under 6 revision approaches. Revisions included changes in the order set content or default settings through 1) population statistics, 2) individualized prediction using machine learning, and 3) clinical knowledge. Revision criteria were determined using electronic health record (EHR) data from 2014 to 2015. Each revision’s clinical appropriateness, workload from using the order set, and generalizability across time were evaluated using EHR data from 2016 and 2017. Our results suggest a potential order set revision approach that jointly leverages clinical knowledge and machine learning to improve usability while updating contents based on latest clinical knowledge and best practices.
Expanding Spectrum of Toxoplasma gondii: Thymoma and Toxoplasmic Encephalitis
Authors: Chastain Daniel B , Sams Joeanna I , Steele Gregory M , Lowder Lindsey O , Franco-Paredes Carlos 
Published: July 2018

Abstract
In this brief report, we describe a 76-year-old patient with thymoma who underwent craniotomy for a left parietal lobe mass with pathologic findings consistent with Toxoplasma gondii encephalitis in the absence of any features of thymoma with immunodeficiency/Good’s syndrome. His clinical course suggested likely Toxoplasma reactivation.
Improving the Sensitivity of Real-time PCR Detection of Group B Streptococcus Using Consensus Sequence-Derived Oligonucleotides
Authors: Khatami Ameneh , Randis Tara M , Chamby Anna , Hooven Thomas A , Gegick Margaret , Suzman Evan , A’Hearn-Thomas Brady , Steenhoff Andrew P , Ratner Adam J 
Published: July 2018

Abstract
Group B Streptococcus (GBS) is a perinatal pathogen and an emerging cause of disease in adults. Culture-independent GBS detection relies on polymerase chain reaction (PCR) of conserved genes, including sip. We demonstrate suboptimal sensitivity of the existing sip PCR strategy and validate an improved method based on consensus sequences from &gt;100 GBS genomes.
Estimation of human-edible protein conversion efficiency, net protein contribution, and enteric methane production from beef production in the United States
Authors: Baber Jessica R , Sawyer Jason E , Wickersham Tryon A 
Published: July 2018

Abstract
A model was developed to estimate beef’s contribution toward meeting human protein requirements using a summative model of net protein contribution (NPC) and methane production. NPC was calculated by multiplying the ratio of human-edible protein (HeP) in beef to the HeP in feedstuffs by the protein quality ratio (PQR). PQR describes the change in biological value of HeP that occurs when plant-derived HeP is converted to beef. An NPC &gt; 1 indicates that the production system is positively contributing to meeting human requirements; systems with NPC &lt; 1 reduce the net protein available to meet human requirements. Scenarios were arranged as a 2 × 2 factorial with two sets of dietary inputs and two sets of production parameters. Dietary inputs represented either inputs used in a previous report estimating HeP (previous diet; PD) or inputs more representative of conventional beef production systems (current diet; CD). Production parameters were either drawn from previous reports (previous parameters; PP) or chosen to characterize current industry standards (current parameters; CP). The HeP conversion efficiency (HePCE) for current industry diets and production parameters (CDCP) (kg HeP yield/kg HeP input) was greatest in the cow–calf sector (2,640.83) compared with stocker (5.22) and feedlot (0.34), and other scenarios followed a similar trend. In addition, the entire production system had an HePCE of 0.99 for CDCP; the previous model diets and production parameters (PDPP) scenario estimated HePCE to be 0.46, and other scenarios were in between. For the CDCP scenario, 56%, 10%, and 34% of the HeP were produced in the cow–calf, stocker, and feedlot sectors; PDPP was similar (59%, 13%, and 28%, respectively). PQR averaged 3.04, 3.04, and 2.64 for cow–calf, stocker, and feedlot sectors, respectively, indicating each sector enhances the biological value of the HeP fed. The NPC was greatest for the cow–calf sector (8,794), followed by the stocker and feedlot sectors (8.85 and 0.23, respectively). The entire beef value chain had a PQR of 2.68 and NPC ranged from 1.01 to 3.11, which correspond to PDPP and CDCP, respectively. Overall, 3.05 kg of CH4 were produced per kilogram HeP for CDCP and 2.58 for PDPP, with the cow–calf sector being greater than the feedlot sector (4.53 vs. 0.94 kg CH4/kg HeP, CDCP). Our results suggest that each individual beef sector and the entire value chain produce more high-quality HeP than is consumed in production. Accordingly, beef is a net contributor to meeting human protein requirements.
Pulmonary manifestations of systemic lupus erythematosus and Sjögren's syndrome
Authors: Lopez Velazquez Marco , Highland Kristin B. 
Published: July 2018

Purpose of review
Systemic lupus erythematosus (SLE) and Sjögren syndrome are chronic autoimmune inflammatory disorders that can present with multiorgan involvement including the lungs. This review will focus on recent literature pertaining to the epidemiology, pathogenesis, clinical presentation and diagnosis and management of SLE and Sjögren syndrome-associated pulmonary conditions.

Recent findings
Pulmonary manifestations of both disease entities have been well characterized and lung involvement can be observed during the course of the disease in most cases. Pulmonary manifestations of SLE and Sjögren syndrome can be classified based on anatomical site of involvement; and the large and small airways, lung parenchyma, lung vasculature, pleura and respiratory muscles can be involved. The pleura is most commonly involved in SLE, whereas the airways are most commonly involved in primary Sjögren's syndrome (pSS). Sleep disturbances have also been described in both entities.

Summary
Although further research into treatment strategies for the pulmonary complications seen in SLE and pSS is needed, the clinician should be aware of the risk factors and clinical presentation of the various pulmonary complications in SLE and pSS in order to identify patients who should be screened and/or have modifications in treatment strategies to mitigate the morbidity and mortality associated with these complications.
Autologous Bone Graft Harvest Using the Reamer–Irrigator–Aspirator
Authors: Yee Michael A. , Hundal Rajbir S. , Perdue Aaron M. , Hake Mark E. 
Published: July 2018

Summary:
Initially developed to reduce intramedullary pressures during long bone intramedullary nail placement, the reamer–irrigator–aspirator (RIA) can be used to harvest large volume autologous bone graft from the intramedullary canal of a long bone. This case-based surgical technique video demonstrates the appropriate techniques that should be applied while using the RIA to obtain autologous bone graft from the femur. A large volume of bone graft, generally between 30 and 90 cm3, can be obtained using a single RIA procedure. The bone graft harvested from the intramedullary canal is excellent regarding its biochemical properties, with several studies reporting higher levels of growth factors and stem cells when compared with iliac crest bone graft. Surgical technique is key to maximize bone graft harvest, as well as to avoid complications including iatrogenic fracture, intraarticular penetration, and fragmentation of either the reamer head from the drive shaft or the guide wire. Pearls and pitfalls regarding sizing of the reamer head, determination of starting point, guide wire placement, reamer advancement, and diligent use of fluoroscopic imaging are highlighted during this video. Finally, outcomes regarding healing of long bone defects when using RIA-derived autologous bone graft and reduction in postoperative pain at the graft donor site are briefly reviewed.
Open Reduction Internal Fixation of the Lisfranc Complex
Authors: Uppal Harmeeth S. 
Published: July 2018

Summary:
Lisfranc injuries are uncommon; however, if left untreated, it can have a detrimental effect causing deformity, chronic pain, and mid-foot arthrosis. Injury can include disruption of the first through fifth tarsometatarsal joints as well as variant patterns that include the involvement of the metatarsals, the naviculocuneiform articulation, and the cuboid. There is controversy regarding the benefits of open reduction internal fixation versus arthrodesis. Regardless, anatomical reduction is paramount to obtaining a good functional outcome. This video details the surgical approach and the reduction and fixation strategy of a high-energy Lisfranc complex fracture dislocation.
Fixation of a Proximal Humerus Fracture Using a Polyaxial Locking Plate and Endosteal Fibular Strut
Authors: Shah Kalpit N. , Sobel Andrew D. , Paxton E. Scott 
Published: July 2018

Summary:
Proximal humerus fractures have a bimodal distribution and are most commonly seen in the elderly and are the third most common fracture pattern seen in the elderly. There is also a subset of these fractures that occur in younger patients secondary to higher energy mechanisms. Nonoperative management is often advocated for a majority of patients, but surgical fixation is often pursued for younger patients or active, older patients with significantly displaced and reconstructable fractures. The most common options for fixation include open reduction and internal fixation with locking plates and intramedullary nailing. Percutaneous pinning and non–locking plate fixation have lost favor with the advent of improved fixation techniques. Recently developed polyaxial locking plates and the use of endosteal fibular strut grafts offer an excellent option for the fixation of these injuries. In this video, we discuss the case of a 47-year-old man with a four-part proximal humerus fracture.