bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep mining heterogeneous networks of biomedical linked data to predict novel drug–target associations
Authors: Zong Nansu , Kim Hyeoneui , Ngo Victoria , Harismendy Olivier 
Published: March 2017

Abstract

Motivation
A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug–target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug–target prediction.

Results
We propose a similarity-based drug–target prediction method that enhances existing association discovery methods by using a topology-based similarity measure. DeepWalk, a deep learning method, is adopted in this study to calculate the similarities within Linked Tripartite Network (LTN), a heterogeneous network generated from biomedical linked datasets. This proposed method shows promising results for drug–target association prediction: 98.96% AUC ROC score with a 10-fold cross-validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN. By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other existing topology-based similarity computation methods, (ii) the performance is better for tripartite than with bipartite networks and (iii) the measure of similarity using network topology outperforms the ones derived from chemical structure (drugs) or genomic sequence (targets). Our proposed methodology proves to be capable of providing a promising solution for drug–target prediction based on topological similarity with a heterogeneous network, and may be readily re-purposed and adapted in the existing of similarity-based methodologies.

Availability and Implementation
The proposed method has been developed in JAVA and it is available, along with the data at the following URL: https://github.com/zongnansu1982/drug-target-prediction.

Supplementary information
Supplementary data are available at Bioinformatics online.
SieveSifter: a web-based tool for visualizing the sieve analyses of HIV-1 vaccine efficacy trials
Authors: Fiore-Gartland Andrew , Kullman Nicholas , deCamp Allan C , Clenaghan Graham , Yang Wayne , Magaret Craig A , Edlefsen Paul T , Gilbert Peter B 
Published: March 2017

Abstract

Summary
Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called ‘sieve analysis’, one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses.

Availability and Implementation
Visualization: http://sieve.fredhutch.org/viz. Source code: https://github.com/nkullman/SIEVE. Data API: http://sieve.fredhutch.org/data.
A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction
Authors: Coassin Stefan , Erhart Gertraud , Weissensteiner Hansi , Eca Guimarães de Araújo Mariana , Lamina Claudia , Schönherr Sebastian , Forer Lukas , Haun Margot , Losso Jamie Lee , Köttgen Anna , Schmidt Konrad , Utermann Gerd , Peters Annette , Gieger Christian , Strauch Konstantin , Finkenstedt Armin , Bale Reto , Zoller Heinz , Paulweber Bernhard , Eckardt Kai-Uwe , Hüttenhofer Alexander , Huber Lukas A. , Kronenberg Florian 
Published: March 2017

Aims
Lp(a) concentrations represent a major cardiovascular risk factor and are almost entirely controlled by one single locus (LPA). However, many genetic factors in LPA governing the enormous variance of Lp(a) levels are still unknown. Since up to 70% of the LPA coding sequence are located in a difficult to access hypervariable copy number variation named KIV-2, we hypothesized that it may contain novel functional variants with pronounced effects on Lp(a) concentrations. We performed a large scale mutation analysis in the KIV-2 using an extreme phenotype approach.

Methods and Results
We compiled an discovery set of 123 samples showing discordance between LPA isoform phenotype and Lp(a) concentrations and controls. Using ultra-deep sequencing, we identified a splice site variant (G4925A) in preferential association with the smaller LPA isoforms. Follow-up in a European general population (n = 2892) revealed an exceptionally high carrier frequency of 22.1% in the general population. The variant explains 20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a) isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL. Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95% confidence interval (CI): 1.17–1.66, P = 1.89e-04] for wildtype LMW individuals to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally positive for G4925A. Functional studies point towards a reduction of splicing efficiency by this novel variant.

Conclusion
A highly frequent but until now undetected variant in the LPA KIV-2 region is strongly associated with reduced Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.
Flawless diamond separation in simultaneous source acquisition by seismic apparition
Authors: Andersson Fredrik , Robertsson Johan O.A. , van Manen Dirk-Jan , Wittsten Jens , Eggenberger Kurt , Amundsen Lasse 
Published: March 2017

Abstract
In this paper we prove that the recently introduced method of signal apparition optimally separates signals from interfering sources recorded during simultaneous source seismic data acquisition. By utilizing a periodic sequence of source signatures along one source line, that wavefield becomes separately partially visible in the spectral domain where it can be isolated from interfering signals, processed, and subtracted from the original recordings, thereby separating the wavefields from each other. Whereas other methods for simultaneous source separation can recover data in a triangle-shaped region in the spectral domain, signal apparition allows for the exact separation of data in a diamond-shaped region that is twice as large thereby enabling superior reconstruction of separated wavefields throughout the entire data bandwidth.
Suppressed star formation by a merging cluster system
Authors: Mansheim A. S. , Lemaux B. C. , Tomczak A. R. , Lubin L. M. , Rumbaugh N. , Wu P.-F. , Gal R. R. , Shen L. , Dawson W. A. , Squires G. K. 
Published: March 2017

Abstract
We examine the effects of an impending cluster merger on galaxies in the large-scale structure (LSS) RX J0910 at z =1.105. Using multiwavelength data, including 102 spectral members drawn from the Observations of Redshift Evolution in Large Scale Environments (ORELSE) survey and precise photometric redshifts, we calculate star formation rates and map the specific star formation rate density of the LSS galaxies. These analyses along with an investigation of the colour–magnitude properties of LSS galaxies indicate lower levels of star formation activity in the region between the merging clusters relative to the outskirts of the system. We suggest that gravitational tidal forces due to the potential of the merging haloes may be the physical mechanism responsible for the observed suppression of star formation in galaxies caught between the merging clusters.
Rare Neurosurgical Complications of Epidural Injections: An 8-Yr Single-Institution Experience
Authors: Smith Gabriel A. , Pace Jonathan , Strohl Madeleine , Kaul Anand , Hayek Salim , Miller Jonathan P. 
Published: March 2017

Abstract

BACKGROUND: Neurosurgical complications from epidural injections have rarely been reported.

OBJECTIVE: To define the spectrum of complications from these procedures in order to identify risk factors and strategies for prevention.

METHODS: A prospectively maintained database of 14 247 neurosurgical admissions over 8 yr was screened to identify patients who had suffered procedural complications associated with 1182 cervical and 4617 lumbar interlaminar epidural injection procedures performed at a single institution. Patients who developed new neurological symptoms or deficits were included. A retrospective analysis of demographic and procedural features was performed.

RESULTS: Thirteen patients experienced complications requiring neurosurgical treatment, accounting for an overall procedural complication rate of 0.22% (0.51% and 0.15% for cervical and lumbar injections, respectively), and representing 0.09% of all neurosurgical admissions over 8 yr. There were 3 categories: hemorrhage (n = 7), infection (n = 3), and inadvertent dural penetration (n = 3). There was significant association with anticoagulation use among patients with hemorrhagic vs nonhemorrhagic complications (P < .01, Fisher's exact test). Six patients who developed epidural hematoma had been managed in accordance with current guidelines, either after prolonged cessation of anticoagulation (n = 3) or taking only aspirin (n = 3); all were decompressed promptly with good long-term outcome. All infections were associated with lumbar injection. Dural penetration resulted in diffuse pneumocephalus (n = 1), intramedullary air at the site of injection (n = 1), and acutely symptomatic colloid cyst (n = 1).

CONCLUSION: A majority of neurosurgical complications from epidural injections are hemorrhagic and associated with anticoagulation, although infection and inadvertent dural penetration also occur. Prompt treatment of compressive lesions is associated with good outcome.
Reduced Sufentanil Doses are Effective for Postoperative Analgesia After Ductal Closure in Extremely Premature Infants
Authors: Soreze Yohan , Audureau Etienne , Decobert Fabrice , Jaby Olivier , Blary Sabine , Danan Claude , Durrmeyer Xavier 
Published: March 2017

Objectives:
The objective of the study was to assess the efficacy of reduced sufentanil doses for postoperative analgesia following surgical ductal closure in extremely premature infants.

Methods:
This was a retrospective, single-center, cohort study comparing 2 sufentanil dosing regimens used between 2001 and 2010 and included all infants born at <28 weeks of gestation with surgical ductal closure. Sufentanil doses were reduced in 2007 as a standard of care. Time was divided into 3 epochs to distinguish the effects of practice changes over time from the effects of sufentanil dose change: epoch 1 (2001 to 2004), epoch 2 (May 2005 to 2007), and epoch 3 (June 2007 to 2010).

Results:
A total of 109 of 114 eligible infants were analyzed (mean [±SD], gestational age: 25.1 [±1.1] wk; mean [±SD], birth weight: 756 [±144] g). Median sufentanil doses were significantly higher during epochs 1 and 2 (0.1 to 0.2 µg/kg/h) than during epoch 3 (0.03 to 0.04 µg/kg/h) (P<0.0001). EDIN (Echelle de Douleur et d’Inconfort du Nouveau-né) pain scores were mostly ≤4 throughout the study period and their changes over time were not contemporaneous with the reduction in sufentanil doses; they were lower during epoch 1 versus epochs 2 and 3 (P<0.0001) and comparable between epochs 2 and 3. Midazolam doses and paracetamol use were not higher during epoch 3 as compared with epochs 1 and 2. No difference in opioid-related adverse events was observed between the 3 epochs.

Conclusion:
Our study supports the use of low continuous intravenous sufentanil doses, consistent with morphine doses currently recommended in this population.
Lumbar Tactile Acuity in Patients With Low Back Pain and Healthy Controls
Authors: Adamczyk Wacław , Luedtke Kerstin , Saulicz Edward 
Published: March 2017

Objective:
Diminished tactile acuity in chronic non-neuropathic pain syndromes has been attributed to central pain processing and cortical reorganization. The latter was recently targeted in clinical trials that demonstrated no clear advantages over traditional approaches for the reduction of nonspecific low back pain (LBP). The aim of this systematic review and meta-analysis was to summarize the current evidence on tactile acuity in LBP and pain-free controls.

Methods:
Six databases were independently searched by 2 researchers. Nineteen studies with either case-control, cross-sectional, or baseline lumbar tactile acuity data collected before an intervention were included in the qualitative and quantitative synthesis. All pooled analyses were based on random effects models. Risk of bias was assessed using the Downs and Black scale and selection criteria were verified independently by 2 assessors.

Results:
Data on patients (n=547) and controls (n=346) were summarized. Studies on patients included data on nonspecific chronic LBP only; no data on acute LBP were identified. There was a significant mean difference between patients and controls for lumbar tactile acuity including (11.74 mm; 95% confidence interval, 8.61-14.87) and excluding (9.49 mm; 95% confidence interval, 3.64-15.34) higher risk of bias studies.

Discussion:
A gap of knowledge regarding tactile acuity in populations with acute and chronic non-neuropathic LBP needs to be addressed in future research as this may significantly help the understanding of the causality of tactile acuity alterations.
The Fear-Avoidance Components Scale (FACS)
Authors: Neblett Randy , Mayer Tom G. , Williams Mark J. , Asih Sali , Cuesta-Vargas Antonio I. , Hartzell Meredith M. , Gatchel Robert J. 
Published: March 2017

Objectives:
To assess the clinical validity and factor structure of the Fear-Avoidance Components Scale (FACS), a new fear-avoidance measure.

Materials and Methods:
In this study, 426 chronic musculoskeletal pain disorder patients were admitted to a Functional Restoration Program (FRP). They were categorized into 5 FACS severity levels, from subclinical to extreme, at admission, and again at discharge. Associations with objective lifting performance and other patient-reported psychosocial measures were determined at admission and discharge, and objective work outcomes for this predominantly disabled cohort, were assessed 1 year later.

Results:
Those patients in the severe and extreme FACS severity groups at admission were more likely to “drop out” of treatment than those in the lower severity groups (P=0.05). At both admission and discharge, the FACS severity groups were highly and inversely correlated with objective lifting performance and patient-reported fear-avoidance–related psychosocial variables, including kinesiophobia, pain intensity, depressive symptoms, perceived disability, perceived injustice, and insomnia (Ps<0.001). All variables showed improvement at FRP discharge. Patients in the extreme FACS severity group at discharge were less likely to return to, or retain, work 1 year later (P≤0.02). A factor analysis identified a 2-factor solution.

Discussion:
Strong associations were found among FACS scores and other patient-reported psychosocial and objective lifting performance variables at both admission and discharge. High discharge-FACS scores were associated with worse work outcomes 1 year after discharge. The FACS seems to be a valid and clinically useful measure for predicting attendance, physical performance, distress, and relevant work outcomes in FRP treatment of chronic musculoskeletal pain disorder patients.
Somatosensory Functions in Survivors of Critical Illness
Authors: Baumbach Philipp , Götz Theresa , Günther Albrecht , Weiss Thomas , Meissner Winfried 
Published: March 2017

Objectives:
There is growing evidence for increased levels of pain and reduced health-related quality of life in survivors of critical illness. Recent studies showed marked small nerve fiber pathology in critically ill patients, which may contribute to chronic pain states and reduced physical recovery after ICU discharge. Primary objective of this study was the comparison of somatosensory functions between survivors of critical illness 6 months after ICU discharge and controls. In post hoc analyses, we aimed to identify associations between small fiber deficits, pain, health-related quality of life, and clinical data.

Design:
Cross-sectional study.

Setting:
Study in critical illness survivors.

Patients:
Critical illness survivors (n = 84) and controls (n = 44).

Interventions:
None.

Measurements and Main Results:
Somatosensory functions were assessed with validated quantitative sensory testing. Pain and pain-related disability were assessed with the chronic pain grade questionnaire. Health-related quality of life was assessed by means of the Short Form-36. Compared with controls, former patients showed significantly increased thermal detection thresholds and more abnormal values in thermal testing, indicating reduced small fiber functioning. In addition, compared to patients without significant small fiber deficits (n = 46, 54.8%), patients with significant small fiber deficits (n = 38, 45.2%) reported higher average pain intensity, pain-related disability, and reduced physical health-related quality of life in the SF-36.

Conclusions:
A large portion of former critically ill patients show small fiber deficits which seem to be associated with increased pain and reduced physical health-related quality of life. Screening of somatosensory functions in the (post-) acute setting could possibly help to identify patients at risk of long-term impairments.
Quantifying the Mortality Impact of Do-Not-Resuscitate Orders in the ICU*
Authors: Fuchs Lior , Anstey Matthew , Feng Mengling , Toledano Ronen , Kogan Slava , Howell Michael D. , Clardy Peter , Celi Leo , Talmor Daniel , Novack Victor 
Published: March 2017

Objectives:
We quantified the 28-day mortality effect of preexisting do-not-resuscitate orders in ICUs.

Design:
Longitudinal, retrospective study of patients admitted to five ICUs at a tertiary university medical center (Beth Israel Deaconess Medical Center, BIDMC, Boston, MA) between 2001 and 2008.

Intervention:
None.

Patients:
Two cohorts were defined: patients with do not resuscitate advance directives on day 1 of ICU admission and a control group comprising patients with no limitations of level of care on ICU day 1 (full code).

Measurements and Main Results:
The primary outcome was mortality at 28 days after ICU admission. Of 19,007 ICU patients, 1,239 patients (6.5%) had a do-not-resuscitate order on the first day of ICU admission and survived 48 hours in the ICU. We matched those do-not-resuscitate patients with 2,402 patients with full-code status. Twenty-eight day and 1-year mortality were both significantly higher in the do-not-resuscitate group (33.9% vs 18.4% and 60.7% vs 40.2%; p < 0.001, respectively).

Conclusion:
Do-not-resuscitate status is an independent risk factor for ICU mortality. This may reflect severity of illness not captured by other clinical factors, but the perceptions of the treating team related to do-not-resuscitate status could also be causally responsible for increased mortality in patients with do-not-resuscitate status.
Exosomes in Critical Illness
Authors: Terrasini Nora , Lionetti Vincenzo 
Published: March 2017

Objective:
Exosomes are small, cell-released vesicles (40–100 nm in size) with the potential to transfer proteins, lipids, small RNAs, messenger RNAs, or DNA between cells via interstitial fluids. Due to their role in tissue homeostasis, exosomes have emerged as a new type of therapeutic and diagnostic (theranostic) tool in the noninvasive assessment of organ response to injury or treatment and in the development of reliable organ-protective intensive therapy. Our review provides current insights into the role of exosomes in the personalized management of injury and repair responses in critical illness.

Data Source:
Data were obtained from a PubMed search of the most recent medical literature, including the PubMed “related articles” search methodology.

Study Selection:
Articles considered include original articles, review articles and conference proceedings.

Data Extraction:
A detailed review of scientific, peer-reviewed data was performed. Relevant pre-clinical and clinical studies were included and summarized.

Data Synthesis:
Current scientific evidence is focused on the following: 1) Frontiers in the management of critical illness; 2) Biogenesis, characterization, and function of circulating exosomes; 3) The role of exosomes in acute lung injury; 4) The role of exosomes in acute cardiac injury; 5) The role of exosomes in acute kidney injury; 6) The role of exosomes in sepsis; 7) Limitations of exosome isolation protocols; and 8) Perspectives in the theranostic use of exosomes.

Conclusions:
Circulating levels of exosomes are associated with the onset and clinical course of critical illness. Exosomes released from cells with different phenotypes exert different functions in order to protect tissue and preserve organ function. Therefore, multifunctional exosomes with combined diagnostic and therapeutic functions show great promise in terms of personalized nanomedicine for patient-specific diagnosis and treatment of critical illness.
In Development—A New Paradigm for Understanding Vascular Disease
Authors: Flavahan Nicholas A. 
Published: March 2017

Abstract:Under physiological conditions, the arterial endothelium exerts a powerful protective influence to maintain vascular homeostasis. However, during the development of vascular disease, these protective activities are lost, and dysfunctional endothelial cells actually promote disease pathogenesis. Numerous investigations have analyzed the characteristics of dysfunctional endothelium with a view to understanding the processes responsible for the dysfunction and to determining their role in vascular pathology. This review adopts an alternate approach: reviewing the mechanisms that contribute to the initial formation of a healthy protective endothelium and on how those mechanisms may be disrupted, precipitating the appearance of dysfunctional endothelial cells and the progression of vascular disease. This approach, which highlights the role of endothelial adherens junctions and vascular endothelial–cadherin in endothelial maturation and endothelial dysfunction, provides new insight into the remarkable biology of this important cell layer and its role in vascular protection and vascular disease.