bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-based prediction of protein– peptide binding regions using Random Forest
Authors: Taherzadeh Ghazaleh , Zhou Yaoqi , Liew Alan Wee-Chung , Yang Yuedong 
Published: September 2017

AbstractMotivationProtein–peptide interactions are one of the most important biological interactions and play crucial role in many diseases including cancer. Therefore, knowledge of these interactions provides invaluable insights into all cellular processes, functional mechanisms, and drug discovery. Protein–peptide interactions can be analyzed by studying the structures of protein–peptide complexes. However, only a small portion has known complex structures and experimental determination of protein–peptide interaction is costly and inefficient. Thus, predicting peptide-binding sites computationally will be useful to improve efficiency and cost effectiveness of experimental studies. Here, we established a machine learning method called SPRINT-Str (Structure-based prediction of protein–Peptide Residue-level Interaction) to use structural information for predicting protein–peptide binding residues. These predicted binding residues are then employed to infer the peptide-binding site by a clustering algorithm.ResultsSPRINT-Str achieves robust and consistent results for prediction of protein–peptide binding regions in terms of residues and sites. Matthews’ Correlation Coefficient (MCC) for 10-fold cross validation and independent test set are 0.27 and 0.293, respectively, as well as 0.775 and 0.782, respectively for area under the curve. The prediction outperforms other state-of-the-art methods, including our previously developed sequence-based method. A further spatial neighbor clustering of predicted binding residues leads to prediction of binding sites at 20–116% higher coverage than the next best method at all precision levels in the test set. The application of SPRINT-Str to protein binding with DNA, RNA and carbohydrate confirms the method‘s capability of separating peptide-binding sites from other functional sites. More importantly, similar performance in prediction of binding residues and sites is obtained when experimentally determined structures are replaced by unbound structures or quality model structures built from homologs, indicating its wide applicability.Availability and implementationhttp://sparks-lab.org/server/SPRINT-StrSupplementary informationSupplementary data are available at Bioinformatics online.
Shared and Disorder-Specific Neurocomputational Mechanisms of Decision-Making in Autism Spectrum Disorder and Obsessive-Compulsive Disorder
Authors: Carlisi Christina O , Norman Luke , Murphy Clodagh M , Christakou Anastasia , Chantiluke Kaylita , Giampietro Vincent , Simmons Andrew , Brammer Michael , Murphy Declan G , Mataix-Cols David , Rubia Katya ,   MRC AIMS consortium
Published: September 2017

AbstractAutism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.
CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice
Authors: Steven Sebastian , Dib Mobin , Hausding Michael , Kashani Fatemeh , Oelze Matthias , Kröller-Schön Swenja , Hanf Alina , Daub Steffen , Roohani Siyer , Gramlich Yves , Lutgens Esther , Schulz Eberhard , Becker Christian , Lackner Karl J , Kleinert Hartmut , Knosalla Christoph , Niesler Beate , Wild Philipp S , Münzel Thomas , Daiber Andreas 
Published: September 2017

Abstract

Aims
CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia.

Methods and results
Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery.

Conclusion
CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.
Discovering foodborne illness in online restaurant reviews
Authors: Effland Thomas , Lawson Anna , Balter Sharon , Devinney Katelynn , Reddy Vasudha , Waechter HaeNa , Gravano Luis , Hsu Daniel 
Published: September 2017

AbstractObjectiveWe developed a system for the discovery of foodborne illness mentioned in online Yelp restaurant reviews using text classification. The system is used by the New York City Department of Health and Mental Hygiene (DOHMH) to monitor Yelp for foodborne illness complaints.Materials and MethodsWe built classifiers for 2 tasks: (1) determining if a review indicated a person experiencing foodborne illness and (2) determining if a review indicated multiple people experiencing foodborne illness. We first developed a prototype classifier in 2012 for both tasks using a small labeled dataset. Over years of system deployment, DOHMH epidemiologists labeled 13 526 reviews selected by this classifier. We used these biased data and a sample of complementary reviews in a principled bias-adjusted training scheme to develop significantly improved classifiers. Finally, we performed an error analysis of the best resulting classifiers.ResultsWe found that logistic regression trained with bias-adjusted augmented data performed best for both classification tasks, with F1-scores of 87% and 66% for tasks 1 and 2, respectively.DiscussionOur error analysis revealed that the inability of our models to account for long phrases caused the most errors. Our bias-adjusted training scheme illustrates how to improve a classification system iteratively by exploiting available biased labeled data.ConclusionsOur system has been instrumental in the identification of 10 outbreaks and 8523 complaints of foodborne illness associated with New York City restaurants since July 2012. Our evaluation has identified strong classifiers for both tasks, whose deployment will allow DOHMH epidemiologists to more effectively monitor Yelp for foodborne illness investigations.
Postdiagnosis Changes in Cigarette Smoking and Survival Following Breast Cancer
Authors: Parada Humberto , Bradshaw Patrick T. , Steck Susan E. , Engel Lawrence S. , Conway Kathleen , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M. , Gammon Marilie D. 
Published: September 2017

Abstract

Background
The purpose of this study was to examine whether at-diagnosis smoking and postdiagnosis changes in smoking within five years after breast cancer were associated with long-term all-cause and breast cancer-specific mortality.

Methods
A population-based cohort of 1508 women diagnosed with first primary in situ or invasive breast cancer in 1996 to 1997 were interviewed shortly after diagnosis and again approximately five years later to assess smoking history. Participants were followed for vital status through December 31, 2014. After 18+ years of follow-up, 597 deaths were identified, 237 of which were breast cancer related. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
Compared with never smokers, risk of all-cause mortality was elevated among the 19% of at-diagnosis smokers (HR = 1.69, 95% CI = 1.36 to 2.11), those who smoked 20 or more cigarettes per day (HR = 1.85, 95% CI = 1.42 to 2.40), women who had smoked for 30 or more years (HR = 1.62, 95% CI = 1.28 to 2.05), and women who had smoked 30 or more pack-years (HR = 1.82, 95% CI = 1.39 to 2.37). Risk of all-cause mortality was further increased among the 8% of women who were at-/postdiagnosis smokers (HR = 2.30, 95% CI = 1.56 to 3.39) but was attenuated among the 11% women who quit smoking after diagnosis (HR = 1.83, 95% CI = 1.32 to 2.52). Compared with never smokers, breast cancer–specific mortality risk was elevated 60% (HR = 1.60, 95% CI = 0.79 to 3.23) among at-/postdiagnosis current smokers, but the confidence interval included the null value and elevated 175% (HR = 2.75, 95% CI = 1.26 to 5.99) when we considered postdiagnosis cumulative pack-years.

Conclusions
Smoking negatively impacts long-term survival after breast cancer. Postdiagnosis cessation of smoking may reduce the risk of all-cause mortality. Breast cancer survivors may benefit from aggressive smoking cessation programs starting as early as the time of diagnosis.
Minimizing Retraction by Pia-Arachnoidal 10-0 Sutures in Intrasulcal Dissection
Authors: Uluc Kutluay , Cikla Ulas , Morkan Deniz B , Sirin Alperen , Ahmed Azam S , Swanson Kyle , Baskaya Mustafa K 
Published: September 2017

Abstract

BACKGROUND
In contemporary microneurosurgery reducing retraction-induced injury to the brain is essential. Self-retaining retractor systems are commonly used to improve visualization and decrease the repetitive microtrauma, but sometimes self-retaining retractor systems can be cumbersome and the force applied can cause focal ischemia or contusions. This may increase the morbidity and mortality. Here, we describe a technique of retraction using 10-0 sutures in the arachnoid.

OBJECTIVE
To evaluate the imaging and clinical results in patients where 10-0 suture retraction was used to aid the surgical procedure.

METHODS
Adjacent cortex was retracted by placing 10-0 nylon suture in the arachnoid of the bank or banks of the sulcus. The suture was secured to the adjacent dural edge by using aneurysm clips, allowing for easy adjustability of the amount of retraction. We retrospectively analyzed the neurological outcome, signal changes in postoperative imaging, and ease of performing surgery in 31 patients with various intracranial lesions including intracranial aneurysms, intra- and extra-axial tumors, and cerebral ischemia requiring arterial bypass.

RESULTS
Clinically, there were no injuries, vascular events, or neurological deficits referable to the relevant cortex. Postoperative imaging did not show changes consistent with ischemia or contusion due to the retraction. This technique improved the visualization and illumination of the surgical field in all cases.

CONCLUSION
Retraction of the arachnoid can be used safely in cases where trans-sulcal dissection is required. This technique may improve initial visualization and decrease the need for dynamic or static retraction.
Effect of Tranexamic Acid on Transfusion: A Randomized Clinical Trial in Acetabular Fracture Surgery
Authors: Lack William D. , Crist Brett D. , Seymour Rachel B. , Harvin William , Karunakar Madhav A. ,   the TXA Study Group‖
Published: September 2017

Objectives:
Given the increasing evidence that minimizing blood loss and limiting allogeneic transfusion can improve patient outcome, we are performing a randomized controlled trial of the use of tranexamic acid (TXA) during acetabular fracture surgery.

Design:
Prospective, multicenter, and randomized.

Setting:
Two level I trauma centers.

Participants:
Eighty-eight patients underwent randomization, with 42 assigned to the TXA group and 46 assigned to the placebo group.

Intervention:
The use of TXA during acetabular fracture surgery.

Main Outcome Measurements:
The primary outcome was allogeneic blood transfusion. Secondary outcomes consisted of estimate blood loss (EBL) and venous thromboembolism (VTE).

Results:
The overall transfusion rate was 40.9% (36 of 88), and the average estimated blood loss was 635 mL. There were no significant differences between groups for transfusion incidence, number of units transfused, EBL, or incidence of VTE. There was no difference in transfusion rate for the TXA group (0.097). Transfusion was significantly more likely in cases with low preoperative hemoglobin levels, higher rates of intraoperative blood loss, and longer surgical times.

Conclusions:
There was no significant difference in transfusion rate, EBL, or VTE for TXA versus placebo. Any potential benefit seems to be overwhelmed by other factors, specifically preoperative anemia and surgical time, which are highly variable in trauma surgery. These findings do not support the routine use of TXA in the setting of open reduction and internal fixation of acetabular fractures.

Level of Evidence:
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Shortening and Angulation Strategies to Address Composite Bone and Soft Tissue Defects
Authors: Pierrie Sarah N. , Hsu Joseph R. 
Published: September 2017

Summary:
Gustilo–Anderson IIIB tibial fractures and infected tibial nonunions represent particular challenges for the orthopaedic trauma surgeon. Debridement of dysvascular bone and soft tissues can create composite bone and soft tissue defects. Restoring the soft tissue envelope is a critical step in preventing or treating ongoing infection and in restoring local blood supply. Shortening and angulation techniques, including the gradual expansion muscle flap, rely on distraction histogenesis to address composite bone and soft tissue loss. These strategies can be used to treat large soft tissue defects when flap coverage or free tissue transfer is not available.
Critical-Sized Bone Defects: Sequence and Planning
Authors: Toogood Paul , Miclau Theodore 
Published: September 2017

Summary:
Bone defects associated with open fractures require a careful approach and planning. At initial presentation, an emergent irrigation and debridement is required. Immediate definitive fixation is frequently safe, with the exception of those injuries that normally require staged management or very severe type IIIB and IIIC injuries. Traumatic wounds that can be approximated primarily should be closed at the time of initial presentation. Wounds that cannot be closed should have a negative pressure wound therapy dressing applied. The need for subsequent debridements remains a clinical judgment, but all nonviable tissue should be removed before definitive coverage. Cefazolin remains the standard of care for all open fractures, and type III injuries also require gram-negative coverage. Both induced membrane technique with staged bone grafting and distraction osteogenesis are excellent options for bony reconstruction. Soft tissue coverage within 1 week of injury seems critical.
Ring Keratitis From Topical Anesthetic Abuse After Laser Epithelial Keratomileusis
Authors: Mergen Burak , Ozdamar Akif , Sarici Ahmet Murat 
Published: September 2017

Abstract:
A 28-year-old man underwent laser epithelial keratomileusis for the correction of myopia in both eyes. The patient subsequently had delayed corneal epithelial healing in both eyes and ring infiltrate in the left eye (LE). Corneal scrapings were obtained from the ocular surface and subjected to microscopic examination and culture. On identifying and preventing the use of topical proparacaine, the corneal epithelium healed in both eyes after the use of eye pressure patches. The ring infiltrate resolved in the patient's LE, leaving minor opacity at the inferior cornea. Refractive surgeons should consider the possibility of topical anesthetic abuse in cases of corneal ring infiltrates. The resulting prognosis can be excellent after the rapid removal of inciting agents and the application of appropriate treatments.
In vivo, chromatin is a fluctuating polymer chain at equilibrium constrained by internal friction
Authors: Socol M. , Wang R. , Jost D. , Carrivain P. , Dahirel V. , Zedek A. , Normand C. , Bystricky K. , Victor J.M. , Gadal O. , Bancaud A. 
Published: September 2017

AbstractChromosome mechanical properties determine DNA folding and dynamics, and underlie all major nuclear functions. Here we combine modeling and real-time motion tracking experiments to infer the physical parameters describing chromatin fibers.In vitro,motion of nucleosome arrays can be accurately modeled by assuming a Kuhn length of 35-55 nm.In vivo, the amplitude of chromosome fluctuations is drastically reduced, and depends on transcription. Transcription activation increases chromatin dynamics only if it involves gene relocalization, while global transcriptional inhibition augments the fluctuations, yet without relocalization. Chromatin fiber motion is accounted for by a model of equilibrium fluctuations of a polymer chain, in which random contacts along the chromosome contour induce an excess of internal friction. Simulations that reproduce chromosome conformation capture and imaging data corroborate this hypothesis. This model unravels the transient nature of chromosome contacts, characterized by a life time of ∼2 seconds and a free energy of formation of ∼1 kBT.
Insights into Hepatitis C Transmission in Young Persons who Inject Drugs: Results From a Dynamic Modeling Approach Informed by State-Level Public Health Surveillance Data
Authors: Gicquelais Rachel E , Foxman Betsy , Coyle Joseph , Eisenberg Marisa C 
Published: September 2017

AbstractRising use of heroin and prescription opioids are major contributors to increases in Hepatitis C Virus (HCV) incidence in US young adults since the late 1990s. How best to interrupt transmission and decrease HCV prevalence in young persons who inject drugs (PWID) is uncertain, but modeling studies in older populations support interventions that increase HCV treatment among all PWID. We developed a transmission model of young (aged 15-30 years) PWID, which we fit to state-level US HCV surveillance data, and simulated the potential impact of primary (reducing injection initiation), secondary (increasing cessation, reducing injection partners, or reducing injection drug use relapse), and tertiary (HCV treatment) interventions on incident and prevalent HCV cases. Interventions with primary prevention initiatives (reducing injection initiation) yielded concurrent reductions to HCV incidence and prevalence. Treatment of former PWID led to prevalence reductions but did not reduce incidence. Treatment of current and former PWID without other interventions led to incidence reductions in scenarios with high injection initiation rates, high syringe sharing, and low relapse rates after injection cessation. While these results are specific to Michigan, our approach could be applied in other states conducting HCV surveillance to identify local-level intervention opportunities.
Whole Genome Bisulphite Sequencing Using the Illumina Hiseq X System
Authors: Suzuki M. , Liao W. , Wos F. , Johnston A.D. , DeGrazia J. , Ishii J. , Bloom T. , Zody M.C. , Germer S. , Greally J.M. 
Published: September 2017

AbstractThe Illumina HiSeq X platform has helped to reduce the cost of whole genome sequencing substantially, but its application for bisulphite sequencing is not straightforward. We describe the optimization of a library preparation and sequencing approach that maximizes the yield and quality of sequencing, and the elimination of a previously unrecognized artefact affecting several percent of bisulphite sequencing reads.
Effector-dependent response deterioration by stochastic transformations reveals mixed reference frames for decisions
Authors: Scott Murdison T. , Standage Dominic , Lefèvre Philippe , Blohm Gunnar 
Published: September 2017

AbstractRecent psychophysical and modeling studies have revealed that sensorimotor reference frame transformations (RFTs) add variability to motor output by decreasing the fidelity of sensory signals. How RFT stochasticity affects the sensory input underlying perceptual decisions, if at all, is unknown. To investigate this, we asked participants to perform a simple two-alternative motion direction discrimination task under varying conditions of head roll and/or stimulus rotation while responding either with a saccade or button press, allowing us to attribute behavioral effects to eye-, head- and shoulder-centered reference frames. We observed a rotation-induced, increase in reaction time and decrease in accuracy, indicating a degradation of motion evidence commensurate with a decrease in motion strength. Inter-participant differences in performance were best explained by a continuum of eye-head-shoulder representations of accumulated decision evidence, with eye- and shoulder-centered preferences during saccades and button presses, respectively. We argue that perceptual decision making and stochastic RFTs are inseparable, consistent with electrophysiological recordings in neural areas thought to be encoding sensorimotor signals for perceptual decisions. Furthermore, transformational stochasticity appears to be a generalized phenomenon, applicable throughout the perceptual and motor systems. We show for the first time that, by simply rolling one’s head, perceptual decision making is impaired in a way that is captured by stochastic RFTs.Significance statementWhen exploring our environment, we typically maintain upright head orientations, often even despite increased energy expenditure. One possible explanation for this apparently suboptimal behavior might come from the finding that sensorimotor transformations, required for generating geometrically-correct behavior, add signal- dependent variability (stochasticity) to perception and action. Here, we explore the functional interaction of stochastic transformations and perceptual decisions by rolling the head and/or stimulus during a motion direction discrimination task. We find that, during visuomotor rotations, perceptual decisions are significantly impaired in both speed and accuracy in a way that is captured by stochastic transformations. Thus, our findings suggest that keeping one’s head aligned with gravity is in fact ideal for making perceptual judgments about our environment.