bluuebunny/crossref_metadata_2025_split huggingface dataset:
The P-mJOA: A Patient-derived, Self-reported Outcome Instrument for Evaluating Cervical Myelopathy
Authors: Rhee John M. , Shi Weilong J. , Cyriac Mathew , Kim Jin Y. , Zhou Feifei , Easley Kirk A. , Patel Anuj 
Published: March 2018

Study Design:
Prospective Cohort Study.

Objective:
The objective of this study is to evaluate and validate a patient-derived version of the modified Japanese Orthopaedic Association (the “P-mJOA”) that a patient can complete along with other patient-derived outcome measures.

Summary of Background Data:
The modified Japanese Orthopaedic Association (mJOA) is a validated instrument widely used in the assessment of cervical myelopathy; however, it is not a patient-derived outcome. If available and reliable, a patient-derived version of the mJOA (P-mJOA) could facilitate research because the data would be immediately available upon patient completion and also remove any potential physician bias. Currently, there is no patient-derived myelopathy survey with the widespread acceptance of the mJOA.

Methods:
The P-mJOA was created by very slightly modifying the verbiage of the mJOA to make it possible for a patient to complete the instrument while maintaining the questionnaire’s core structure. A total of 100 consecutive consenting patients with cervical myelopathy were enrolled. After the patient completed the P-mJOA, the mJOA was scored by a physician blinded to the P-mJOA result.

Results:
The P-mJOA and the mJOA had identical mean scores of 14.7 (mean difference±SD: 0.0±1.5; P=0.89). Several measures of reliability demonstrated agreement between the 2 surveys, including strong agreement with the intraclass correlation coefficient and Spearman ρ (both 0.83) and moderate to substantial agreement with weighted κ values (0.55 to 0.66). In addition, 67% of patients preferred to fill out the P-mJOA themselves, suggesting low patient burden.

Conclusions:
The P-mJOA provided identical mean scores to the mJOA in assessing myelopathy with moderate to strong agreement. Comprised of the same 4 questions as the mJOA but slightly reworded for patient comprehension, the P-mJOA also demonstrated low patient burden in completing the survey. We believe the P-mJOA is a promising tool in cervical myelopathy research with the benefits of a patient-derived outcome measure and low patient burden.

Level of Evidence:
Level II.
The Risks of Hepatitis C in Association With Cervical Spinal Surgery
Authors: Lavian Joshua D. , Murray Daniel P. , Hollern Douglas A. , Bloom Lee , Shah Neil V. , Gewolb Daniel , Segreto Frank A. , Powell Shahla , Messina James C. , Naziri Qais , Yoshihara Hiroyuki , Paulino Carl B. , Diebo Bassel G. 
Published: March 2018

Study Design:
Retrospective review.

Objective:
To investigate rates of in-hospital postsurgical complications among hepatitis C-infected patients after cervical spinal surgery in comparison with uninfected patients and determine independent risk factors.

Summary of Background Data:
Studying hepatitis C virus (HCV) as a possible risk factor for cervical spine postoperative complications is prudent, given the high prevalence of cervical spondylosis and HCV in older patients. Spine literature is limited with respect to the impact of chronic HCV upon complications after surgery.

Materials and Methods:
Patients who underwent cervical spine surgery for cervical radiculopathy (CR) or cervical myelopathy (CM) from 2005 to 2013 were retrospectively reviewed using the Nationwide Inpatient Sample database. Patients were divided into CR and CM groups, with comparative subgroup analysis of HCV and no-HCV patients. Univariate analysis compared demographics and complications. Binary logistic stepwise regression modeling identified any independent outcome predictors (covariates: age, sex, Deyo score, and surgical approach).

Results:
In total, 227,310 patients (HCV: n=2542; no-HCV: n=224,764) were included. From 2005 to 2013, HCV infection prevalence among all cervical spinal fusion cases increased from 0.8% to 1.2%. HCV patients were more likely to be African American or Hispanic and have Medicare and/or Medicaid (all P<0.001). Overall complication rates among HCV patients with CR or CM increased, specifically related to device (CR: 3.1% vs. 1.9%; CM: 2.9% vs. 1.3%), hematoma/seroma (CR: 1.1% vs. 0.4%; CM: 1.8% vs. 0.8%), and sepsis (CR: 0.4% vs. 0.1%; CM: 1.1% vs. 0.5%) (all P≤0.001). Among CR and CM patients, HCV significantly predicted increased complication rates [odds ratio (OR): 1.268; OR: 1.194], hospital stay (OR: 1.738; OR: 1.861), and hospital charges (OR: 1.516; OR: 1.732; all P≤0.044).

Conclusions:
HCV patients undergoing cervical spinal surgery were found to have increased risks of postoperative complications and increased risk associated with surgical approach. These findings should augment preoperative risk stratification and counseling for HCV patients and their spine surgeons.

Level of Evidence:
Level III.
Using a Patient-Centered Approach to Identify Symptom Clusters Among Adolescents With Cancer
Authors: Wu Wei-Wen , Lin Kuan-Chia , Liang Shu-Yuan , Jou Shiann-Tarng 
Published: March 2018

Background
Prior studies identifying symptom clusters used a symptom-centered approach to demonstrate the relationship among symptoms. Latent profile analysis (LPA) is a patient-centered approach that classifies individuals from a heterogeneous population into homogeneous subgroups, helping prioritize interventions to focus on clusters with the most severe symptom burden.

Objective
The aim of this study was to use LPA to determine the best-fit models and to identify phenotypes of severe symptom distress profiles for adolescents with cancer who are undergoing treatment and in survivorship.

Methods
We used estimated means generated by the LPA to predict the probability of an individual symptom occurring across on- and off-treatment groups for 200 adolescents with cancer.

Results
The 3-profile solution was considered the best fit to the data for both on- and off-treatment groups. Adolescents on treatment and classified into the severe profile were most likely to report distress in appetite, fatigue, appearance, nausea, and concentration. Adolescents off treatment and classified into the severe profile were most likely to report distress in fatigue, pain frequency, and concentration.

Conclusions
Latent profile analysis provided a cluster methodology that uncovered hidden profiles from observed symptoms. This made it possible to directly compare the phenotypes of severe profiles between different treatment statuses.

Implications for Practice
The co-occurring 13-item Symptom Distress Scale symptoms found in the severe symptom distress profiles could be used as items in a prespecified severe symptom distress cluster, helping evaluate a patient's risk of developing varying degrees of symptom distress.
Incident Reporting to Improve Patient Safety
Authors: O'Connell Karen J. , Shaw Kathy N. , Ruddy Richard M. , Mahajan Prashant V. , Lichenstein Richard , Olsen Cody S. , Funai Tomohiko , Blumberg Stephen , Chamberlain James M. 
Published: March 2018

Objective
Medical errors threaten patient safety, especially in the pediatric emergency department (ED) where overcrowding, multiple handoffs, and workflow interruptions are common. Errors related to process variance involve situations that are not consistent with standard ED operations or routine patient care.

Setting/Participants
We performed a planned subanalysis of the Pediatric Emergency Care Applied Research Network incident reporting data classified as process variance events. Confidential deidentified incident reports (IRs) were collected and classified by 2 independent investigators. Events categorized as process variance were then subtyped for severity and contributing factors. Data were analyzed using descriptive statistics.

Outcome Measures
The study intention was to describe and measure reported medical errors related to process variance in 17 EDs in the Pediatric Emergency Care Applied Research Network from 2007 to 2008.

Results
Between July 2007 and June 2008, 2906 eligible reports were reviewed. Process variance events were identified in 15.4% (447/2906). The majority were related to patient flow (35.4%), handoff communication (17.2%), and patient identification errors (15.9%). Most staff involved included nurses (47.9%) and physicians (28%); trainees were infrequently reported. The majority of events did not result in harm (65.7%); 17.9% (80/447) of cases were classified as unsafe conditions but did not reach the patient. Temporary harm requiring further treatment or hospitalization was reported in 5.6% (25/447). No events resulted in permanent harm, near death, or death. Contributing factors included human factors (92.1%), in particular handoff communication, interpersonal skills, and compliance with established procedures, and system-level errors (18.1%), including unclear or unavailable policies and inadequate staffing levels.

Conclusions
Although process variance events accounted for approximately 1 in 6 reported safety events, very few led to patient harm. Because human and system-level factors contributed to most of these events, our data provide an insight into potential areas for further investigation and improvements to mitigate errors in the ED setting.
Posttraumatic High-Flow Nonischemic Priapism
Authors: Nalbant Ismail , Tuygun Can , Gücük Adnan , Conkbayir Isik , Oztürk Ufuk , Yilmaz Muhammed Sahin , İmamoglu Muhammed Abdurrahim 
Published: March 2018

Abstract
Priapism is an uncommon disorder, and nonischemic priapism is seen less frequently in children, generally after trauma. Although it seems to be an advantage that urgent intervention is not required because of no cavernous ischemia, it is likely to be misdiagnosed because of the asymptomatic potential. We aimed to present a case of posttraumatic nonischemic priapism.
Conjugated Hyperbilirubinemia in the Neonate and Young Infant
Authors: Weiss Anna K. , Vora Parag V. 
Published: March 2018

Abstract
Cholestatic jaundice in the first few weeks of life may herald potentially life-threatening pathology. It is therefore incumbent upon the pediatric practitioner to have a high index of suspicion for severe disease when investigating jaundice in a young infant. This article outlines the epidemiology, pathophysiology, differential diagnosis, and diagnostic workup for both the most common and the most severe causes of cholestasis in the neonatal period.
Wound Surface Area as a Risk Factor for Flap Complications among Patients with Open Fractures
Authors: Shea Phelan , O’Hara Nathan N. , Sprague Sheila A. , Bhandari Mohit , Petrisor Brad A. , Jeray Kyle J. , Zhan Min , Slobogean Gerard P. , Pensy Raymond A. 
Published: March 2018

Background:
Soft-tissue complications often dictate the success of limb salvage and the overall outcome of open fractures. Based on prior work at the R Adams Cowley Shock Trauma Center, the authors hypothesize that wounds larger than 200 cm2 are associated with a greater likelihood of both flap-related reoperation and wound complications among patients requiring soft-tissue reconstruction with a rotational flap or free tissue transfer.

Methods:
This study was a secondary analysis of Fluid Lavage in Open Wounds trial data that included all patients who received a rotational or free tissue flap transfer for an open fracture. The primary outcome was flap-related reoperation within 12 months of injury. The secondary outcome was wound complication, which included events treated operatively or nonoperatively. Multivariable logistic regression was used to assess the association between wound size and outcomes, adjusting for confounders.

Results:
Seventeen percent of the 112 patients required a flap-related reoperation. A wound size greater than 200 cm2 was not associated with reoperation in an unadjusted model (p = 0.64) or adjusting for Gustilo type (p = 0.70). The sample had an overall wound complication rate of 47.3 percent. Patients with a wound size of greater than 200 cm2 were three times more likely to experience wound complications (OR, 3.05; 95 percent CI, 1.08 to 8.62; p = 0.04) when adjusting for moderate to severe wound contamination and wound closure in the operating room.

Conclusion:
The findings of this study demonstrate that wound surface area is an integral determinant for wound complication following soft-tissue flap treatment, but found no association between wound surface area and flap-related reoperation rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Accurate assembly of minority viral haplotypes from next-generation sequencing through efficient noise reduction
Authors: Knyazev Sergey , Tsyvina Viachaslau , Shankar Anupama , Melnyk Andrew , Artyomenko Alexander , Malygina Tatiana , Porozov Yuri B. , Campbell Ellsworth M. , Mangul Serghei , Switzer William M. , Skums Pavel , Zelikovsky Alex 
Published: March 2018

ABSTRACTRapidly evolving RNA viruses continuously produce minority haplotypes that can become dominant if they are drug-resistant or can better evade the immune system. Therefore, early detection and identification of minority viral haplotypes may help to promptly adjust the patient's treatment plan preventing potential disease complications. Minority haplotypes can be identified using next-generation sequencing (NGS), but sequencing noise hinders accurate identification. The elimination of sequencing noise is a non-trivial task that still remains open. Here we propose CliqueSNV based on extracting pairs of statistically linked mutations from noisy reads. This effectively reduces sequencing noise and enables identifying minority haplotypes with the frequency below the sequencing error rate. We comparatively assess the performance of CliqueSNV using an in vitro mixture of nine haplotypes that were derived from the mutation profile of an existing HIV patient. We show that CliqueSNV can accurately assemble viral haplotypes with frequencies as low as 0.1% and maintains consistent performance across short and long bases sequencing platforms.
The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations
Authors: Ramasubramanian Smiruthi , Rudy Yoram 
Published: March 2018

ABSTRACTRelating ion-channel (iCh) structural dynamics to physiological function remains a challenge. Current experimental and computational techniques have limited ability to explore this relationship in atomistic detail over physiological timescales. A framework associating iCh structure to function is necessary for elucidating normal and disease mechanisms. We formulated a modeling schema that overcomes the limitations of current methods through applications of Artificial Intelligence Machine Learning (ML). Using this approach, we studied molecular processes that underlie human IKs voltage mediated gating. IKs malfunction underlies many debilitating and life-threatening diseases. Molecular components of IKs that underlie its electrophysiological function include KCNQ1 (pore forming tetramer) and KCNE1 (auxiliary subunit). Simulations, using the IKs structure-function model, reproduced experimentally recorded saturation of gating charge displacement at positive membrane voltages, two-step voltage sensor (VS) movement shown by fluorescence, iCh gating statistics, and current-voltage (I-V) relationship. New mechanistic insights include - (1) pore energy profile determines iCh subconductance (SC), (2) entire protein structure, not limited to the pore, contributes to pore energy and channel SC, (3) interactions with KCNE1 result in two distinct VS movements, causing gating charge saturation at positive membrane voltages and current activation delay, and (4) flexible coupling between VS and pore permits pore opening at lower VS positions, resulting in sequential gating. The new modeling approach is applicable to atomistic scale studies of other proteins on timescales of physiological function.
DIMEdb: an integrated database and web service for metabolite identification in direct infusion mass spectrometery
Authors: O’Shea Keiron , Kattupalli Divya , Mur Luis AJ , Hardy Nigel W , Misra Biswapriya B , Lu Chuan 
Published: March 2018

AbstractMotivationMetabolomics involves the characterisation, identification, and quantification of small molecules (metabolites) that act as the reaction intermediates of biological processes. Over the past few years, we have seen wide scale improvements in data processing, database, and statistical analysis tools. Direct infusion mass spectrometery (DIMS) is a widely used platform that is able to produce a global fingerprint of the metabolome, without the requirement of a prior chromatographic step - making it ideal for wide scale high-throughput metabolomics analysis. In spite of these developments, metabolite identification still remains a key bottleneck in untargeted mass spectrometry-based metabolomics studies. The first step of the metabolite identification task is to query masses against a metaboite database to get putative metabolite annotations. Each existing metabolite database differs in a number of aspects including coverage, format, and accessibility - often limiting the user to a rudimentary web interface. Manually combining multiple search results for a single experiment where there may be potentially hundreds of masses to investigate becomes an incredibly arduous task.ResultsTo facilitate unified access to metabolite information we have created the Direct Infusion MEtabolite database (DIMEdb), a comprehensive web-based metabolite database that contains over 80,000 metabolites sourced from a number of renowned metabolite databases of which can be utilised in the analysis and annotation of DIMS data. To demostrate the efficacy of DIMEdb, a simple use case for metabolic identification is presented. DIMEdb aims to provide a single point of access to metabolite information, and hopefully facilitate the development of much needed bioinformatic tools.AvailabilityDIMEdb is freely available at https://dimedb.ibers.aber.ac.uk.Contactkeo7@aber.ac.ukSupplementary informationSupplementary data are available at Bioinformatics online.
Locomotor response to acute stressors requires hypothalamic-pituitary-interrenal axis activation and glucocorticoid receptor
Authors: Lee Han B. , Schwab Tanya L. , Sigafoos Ashley N. , Gauerke Jennifer L. , Krug Randall G. , Serres MaKayla R. , Jacobs Dakota C. , Cotter Ryan P. , Das Biswadeep , Petersen Morgan O. , Daby Camden L. , Urban Rhianna M. , Berry Bethany C. , Clark Karl J. 
Published: March 2018

AbstractWhen vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response (SR). Rapid physiological changes in heart rate and blood sugar levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic-pituitary-adrenal (HPA) axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent HPA axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires HPI axis activation. In teleost fish, interrenal cells (I) are functionally homologous to the adrenal gland cortical layer. We derived 8 frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 ofmc2r(adrenocorticotropic hormone receptor), two in each of exon 2 and exon 5 ofnr3c1(glucocorticoid receptor), and two in exon 2 ofnr3c2(mineralocorticoid receptor). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show here that this locomotor response requires a functioning HPI axis via the action ofmc2r(adrenocorticotropic hormone receptor) and the canonical glucocorticoid receptor encoded bynr3c1gene, but not mineralocorticoid receptor (nr3c2). Our rapid behavioral assay paradigm based on HPI axis biology may prove useful to screen for genetic, pharmacological, or environmental modifiers of the HPA axis.SignificanceAltered HPA axis activity is acknowledged as a causative and critical prognostic factor in many psychiatric disorders including depression. Nonetheless, genome wide association studies (GWAS) on depression have revealed conflicting findings about susceptibility loci, while identifying several genetic loci that warrant further investigations in the process. Such findings indicate that psychiatric disorders with complex genetic foundations require functional studies as well as genetic analyses. We developed a sensitive behavioral assay paradigm that leverages the genetic amenability and rapid development of zebrafish and demonstrated that our assay system reliably detects changes in HPA axis responsiveness. Our functional genetics and behavioral assay approach provides a useful platform to discover novel genetic, pharmacological, or environmental modifiers of the HPA axis.
Trends in outpatient antibiotic prescribing practice among US older adults, 2011-2015: an observational study
Authors: Olesen Scott W. , Barnett Michael L. , MacFadden Derek R. , Lipsitch Marc , Grad Yonatan H. 
Published: March 2018

Structured abstractObjectiveTo identify temporal trends in outpatient antibiotic use and antibiotic prescribing practice among older adults.DesignObservational study using United States Medicare administrative claims during 2011-2015. Trends in antibiotic use were estimated using multivariable regression adjusting for beneficiaries’ demographic and clinical covariates.SettingMedicare.Participants4.6 million Medicare beneficiaries from a nationwide, 20% sample of fee-forservice Medicare beneficiaries ≥65 years old.Main outcome measurementsOverall rates of antibiotic prescription claims, rates of appropriate and inappropriate prescribing, rates for each of the most frequently prescribed antibiotics, and rates of antibiotic claims associated with specific diagnoses.ResultsAntibiotic claims fell from 1362.2 to 1361.6 claims per 1,000 beneficiaries per year during 2011-2015, an overall 0.2% decrease (95% CI 0.07-0.32). Inappropriate antibiotic claims fell from 552 to 533 claims per 1,000 beneficiaries, a 4.1% decrease (CI 3.9-4.3). Individual antibiotics had heterogeneous changes in use. For example, azithromycin claims per beneficiary decreased by 18.4% (CI 18.2-18.7) while levofloxacin claims increased by 28.1% (CI 27.5-28.6). Azithromycin use associated with each of the potentially appropriate and inappropriate respiratory diagnoses we considered decreased, while levofloxacin use associated with each of those diagnoses increased.ConclusionAmong US Medicare beneficiaries, overall antibiotic use and inappropriate use declined modestly, but individual drugs experienced divergent changes in use. Trends in drug use across indications were stronger than trends in use for individual indications, suggesting that guidelines and concerns about antibiotic resistance were not major drivers of change in antibiotic use.