bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics
Authors: Davies Katherine M. , Mercer Julian F.B. , Chen Nicholas , Double Kay L. 
Published: March 2016

Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease.
Maximum power point tracking control method for proton exchange membrane fuel cell
Authors: Wang Meng Hui , Huang Mei‐Ling , Jiang Wei‐Jhe , Liou Kang‐Jian 
Published: March 2016

The load and hydrogen pressure changes in a proton exchange membrane fuel cell (PEMFC) result in instability and reduce the efficiency of the output power. This study proposes an extension sliding mode controller (ESMC) for maximum power point tracking (MPPT) of the fuel cells to enhance system efficiency and to reach the steady state of the output power. The experimental platform is set at a 200‐watt PEMFC in this study. Results show that the tracking speed of the ESMC is 0.95 s, and the booster conversion efficiency is 94.5%; both are superior to other conventional MPPT methods. This study demonstrates a number of key technologies for renewable energy systems.
Generation, performance evaluation and control design of single‐phase differential‐mode buck–boost current‐source inverters
Authors: Darwish Ahmed , Massoud Ahmed , Holliday Derrick , Ahmed Shehab , Williams Barry 
Published: March 2016

Differential‐mode inverter topologies are promising for renewable energy generation since they offer advantages such as passive elements sizes reduction, having decreased power losses and reduced total cost. Single phase buck–boost differential‐mode current‐source inverters (DMCSIs) can deliver wider range of output voltage above or below the input dc voltage, which is necessary for high‐efficiency modern renewable energy applications. Since these inverters have continuous input currents, they are suitable for maximum power point tracking (MPPT) operation of photovoltaic systems. Yet, the investigation, operation and implementation of these types of inverters have not been extensively discussed. As a drawback, the total dc side input current of a single‐phase inverter consists of a dc component and an undesirable ac component. This ac component frequency is double the output voltage frequency and thus it affects MPPT resulting in reduced total efficiency. In this study, five promising DMCSIs are proposed and compared in terms of their total efficiencies, high‐frequency ripple current in the dc side, total harmonic distortion, devices sizes and ratings. Moreover, the sliding mode controller's design and possible methods of eliminating the input second harmonic current are discussed. 2.5 kW bidirectional inverters are implemented to confirm the design flexibility of the proposed DMCSIs.
Goldilocks: a tool for identifying genomic regions that are ‘just right’
Authors: Nicholls Samuel M. , Clare Amanda , Randall Joshua C. 
Published: March 2016

Abstract
Summary: We present Goldilocks: a Python package providing functionality for collecting summary statistics, identifying shifts in variation, discovering outlier regions and locating and extracting interesting regions from one or more arbitrary genomes for further analysis, for a user-provided definition of interesting.
Availability and implementation: Goldilocks is freely available open-source software distributed under the MIT licence. Source code is hosted publicly at https://github.com/SamStudio8/goldilocks and the package may also be installed using pip install goldilocks. Documentation can be found at https://goldilocks.readthedocs.org.
Contact: msn@aber.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Branch: an interactive, web-based tool for testing hypotheses and developing predictive models
Authors: Gangavarapu Karthik , Babji Vyshakh , Meißner Tobias , Su Andrew I. , Good Benjamin M. 
Published: March 2016

Abstract
Summary: Branch is a web application that provides users with the ability to interact directly with large biomedical datasets. The interaction is mediated through a collaborative graphical user interface for building and evaluating decision trees. These trees can be used to compose and test sophisticated hypotheses and to develop predictive models. Decision trees are built and evaluated based on a library of imported datasets and can be stored in a collective area for sharing and re-use.
Availability and implementation: Branch is hosted at http://biobranch.org/ and the open source code is available at http://bitbucket.org/sulab/biobranch/.
Contacts: asu@scripps.edu or bgood@scripps.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Visual Omics Explorer (VOE): a cross-platform portal for interactive data visualization
Authors: Kim Baekdoo , Ali Thahmina , Hosmer Samuel , Krampis Konstantinos 
Published: March 2016

Abstract
Motivation: Given the abundance of genome sequencing and omics data, an opprtunity and challenge in bioinformatics relates to data mining and visualization. The majority of current bioinformatics visualizations are implemented either as multi-tier web server applications that require significant maintenance effort, or as client software that presumes technical expertise for installation. Here we present the Visual Omics Explorer (VOE), a cross-platform data visualization portal that is implemented using only HTML and Javascript code. VOE is a standalone software that can be loaded offline on the web browser from a local copy of the code, or over the internet without any dependency other than distributing the code through a file sharing service. VOE can interactively display genomics, transcriptomics, epigenomics and metagenomics data stored either locally or retrieved from cloud storage services, and runs on both desktop computers and mobile devices.
Availability and implementation: VOE is accessible at http://bcil.github.io/VOE/.
Contact: agbiotec@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
ORFanFinder: automated identification of taxonomically restricted orphan genes
Authors: Ekstrom Alex , Yin Yanbin 
Published: March 2016

Abstract
Motivation: Orphan genes, also known as ORFans, are newly evolved genes in a genome that enable the organism to adapt to specific living environment. The gene content of every sequenced genome can be classified into different age groups, based on how widely/narrowly a gene’s homologs are distributed in the context of species taxonomy. Those having homologs restricted to organisms of particular taxonomic ranks are classified as taxonomically restricted ORFans.
Results: Implementing this idea, we have developed an open source program named ORFanFinder and a free web server to allow automated classification of a genome’s gene content and identification of ORFans at different taxonomic ranks. ORFanFinder and its web server will contribute to the comparative genomics field by facilitating the study of the origin of new genes and the emergence of lineage-specific traits in both prokaryotes and eukaryotes.
Availability and implementation: http://cys.bios.niu.edu/orfanfinder
Contact: yyin@niu.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring
Authors: Graham Susan M. , Chohan Vrasha , Ronen Keshet , Deya Ruth W. , Masese Linnet N. , Mandaliya Kishor N. , Peshu Norbert M. , Lehman Dara A. , McClelland R. Scott , Overbaugh Julie 
Published: March 2016

Abstract
Background.  The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy.
Methods.  Treatment failure was diagnosed based on World Health Organization (WHO) clinical or immunologic criteria, and second-line therapy was initiated. Stored plasma and genital samples were tested to determine the presence and timing of virologic failure and emergence of drug resistance. The median duration of genital shedding of genotypically resistant virus prior to regimen switch was estimated.
Results.  Nineteen of 184 women were diagnosed with treatment failure, of whom 12 (63.2%) had confirmed virologic failure at the switch date. All 12 women with virologic failure (viral load, 5855–1 086 500 copies/mL) had dual-class resistance in plasma. Seven of the 12 (58.3%) had genital HIV-1 RNA levels high enough to amplify (673–116 494 copies/swab), all with dual-class resistance. The median time from detection of resistance in stored samples to regimen switch was 895 days (95% confidence interval [CI], 130–1414 days) for plasma and 629 days (95% CI, 341–984 days) for genital tract secretions.
Conclusions.  Among women diagnosed with treatment failure using WHO clinical or immunologic criteria, over half had virologic failure confirmed in stored samples. Resistant HIV-1 RNA was shed in the genital tract at detectable levels for ≈1.7 years before failure diagnosis, with steady accumulation of mutations. These findings add urgency to the ongoing scale-up of viral load testing in resource-limited settings.
Medical Student Perceptions of the Learning Environment at the End of the First Year: A 28-Medical School Collaborative
Authors: Skochelak Susan E. , Stansfield R. Brent , Dunham Lisette , Dekhtyar Michael , Gruppen Larry D. , Christianson Charles , Filstead William , Quirk Mark 
Published: March 2016

Purpose
Accreditation and professional organizations have recognized the importance of measuring medical students’ perceptions of the learning environment, which influences well-being and professional competency development, to optimize professional development. This study was conducted to explore interactions between students’ perceptions of the medical school learning environment, student demographic variables, and students’ professional attributes of empathy, coping, tolerance of ambiguity, and patient-centeredness to provide ideas for improving the learning environment.

Method
Twenty-eight medical schools at 38 campuses recruited 4,664 entering medical students to participate in the two-cohort longitudinal study (2010–2014 or 2011–2015). The authors employed chi-square tests and analysis of variance to examine the relationship between Medical School Learning Environment Survey (MSLES) scores and student characteristics. The authors used mixed-effects models with random school and campus effects to test the overall variances accounted for in MSLES scores at the end of the first year of medical school.

Results
Student attributes and demographic characteristics differed significantly across schools but accounted for only 2.2% of the total variance in MSLES scores. Medical school campus explained 15.6% of the variance in MSLES scores.

Conclusions
At year’s end, students’ perceptions toward the learning environment, as reported on the MSLES, differed significantly according to the medical school campus where they trained. Further studies are needed to identify specific factors, such as grading policies, administrative support, and existence of learning communities, which may influence perceptions of the learning environment at various schools. Identifying such variables would assist schools in developing a positive learning environment.
Building a Framework of Entrustable Professional Activities, Supported by Competencies and Milestones, to Bridge the Educational Continuum
Authors: Carraccio Carol , Englander Robert , Gilhooly Joseph , Mink Richard , Hofkosh Dena , Barone Michael A. , Holmboe Eric S. 
Published: March 2016

The transition to competency-based medical education (CBME) and adoption of the foundational domains of competence by the Accreditation Council for Graduate Medical Education, Association of American Medical Colleges (AAMC), and American Board of Medical Specialties’ certification and maintenance of certification (MOC) programs provided an unprecedented opportunity for the pediatrics community to create a model of learning and assessment across the continuum. Two frameworks for assessment in CBME have been promoted: (1) entrustable professional activities (EPAs) and (2) milestones that define a developmental trajectory for individual competencies. EPAs are observable and measureable units of work that can be mapped to competencies and milestones critical to performing them safely and effectively.
The pediatrics community integrated the two frameworks to create a potential pathway of learning and assessment across the continuum from undergraduate medical education (UME) to graduate medical education (GME) and from GME to practice. The authors briefly describe the evolution of the Pediatrics Milestone Project and the process for identifying EPAs for the specialty and subspecialties of pediatrics. The method of integrating EPAs with competencies and milestones through a mapping process is discussed, and an example is provided. The authors illustrate the alignment of the AAMC’s Core EPAs for Entering Residency with the general pediatrics EPAs and, in turn, the alignment of the latter with the subspecialty EPAs, thus helping build the bridge between UME and GME. The authors propose how assessment in GME, based on EPAs and milestones, can guide MOC to complete the bridge across the education continuum.
Prediction of Large Vessel Occlusions in Acute Stroke: National Institute of Health Stroke Scale Is Hard to Beat*
Authors: Vanacker Peter , Heldner Mirjam R. , Amiguet Michael , Faouzi Mohamed , Cras Patrick , Ntaios George , Arnold Marcel , Mattle Heinrich P. , Gralla Jan , Fischer Urs , Michel Patrik 
Published: March 2016

Objectives:
Endovascular treatment for acute ischemic stroke with a large vessel occlusion was recently shown to be effective. We aimed to develop a score capable of predicting large vessel occlusion eligible for endovascular treatment in the early hospital management.

Design:
Retrospective, cohort study.

Setting:
Two tertiary, Swiss stroke centers.

Patients:
Consecutive acute ischemic stroke patients (1,645 patients; Acute STroke Registry and Analysis of Lausanne registry), who had CT angiography within 6 and 12 hours of symptom onset, were categorized according to the occlusion site. Demographic and clinical information was used in logistic regression analysis to derive predictors of large vessel occlusion (defined as intracranial carotid, basilar, and M1 segment of middle cerebral artery occlusions). Based on logistic regression coefficients, an integer score was created and validated internally and externally (848 patients; Bernese Stroke Registry).

Interventions:
None.

Measurements and Main Results:
Large vessel occlusions were present in 316 patients (21%) in the derivation and 566 (28%) in the external validation cohort. Five predictors added significantly to the score: National Institute of Health Stroke Scale at admission, hemineglect, female sex, atrial fibrillation, and no history of stroke and prestroke handicap (modified Rankin Scale score, < 2). Diagnostic accuracy in internal and external validation cohorts was excellent (area under the receiver operating characteristic curve, 0.84 both). The score performed slightly better than National Institute of Health Stroke Scale alone regarding prediction error (Wilcoxon signed rank test, p < 0.001) and regarding discriminatory power in derivation and pooled cohorts (area under the receiver operating characteristic curve, 0.81 vs 0.80; DeLong test, p = 0.02).

Conclusions:
Our score accurately predicts the presence of emergent large vessel occlusions, which are eligible for endovascular treatment. However, incorporation of additional demographic and historical information available on hospital arrival provides minimal incremental predictive value compared with the National Institute of Health Stroke Scale alone.
Prevalence and Characteristics of Chronic Intensive Care–Related Pain: The Role of Severe Sepsis and Septic Shock
Authors: Baumbach Philipp , Götz Theresa , Günther Albrecht , Weiss Thomas , Meissner Winfried 
Published: March 2016

Objective:
There is only limited knowledge about chronic pain conditions resulting from critical care. Experimental and clinical data suggest a close relationship between inflammation and pain perception. Since sepsis is the most severe form of systemic inflammation, the primary objective was to evaluate chronic pain states and functional impairment of septic and nonseptic patients 6 months after discharge from ICU. Second, we aimed to obtain the total prevalence and characteristics of chronic ICU-related pain.

Design:
Case-control study.

Setting:
Observational study in long-term survivors of mixed surgical and medical ICUs.

Patients:
Septic and nonseptic survivors of critical care (n = 207) and healthy controls (n = 46).

Interventions:
None.

Measurements and Main Results:
We collected comprehensive information on patients’ past and present pain 6 months after ICU discharge by means of the German pain questionnaire. Pain intensity levels and pain interference ratings were compared between septic and nonseptic patients and healthy controls. We found no differences in prevalence, severity, and interference of pain between septic and nonseptic patients. However, both patient groups differed significantly from controls. In secondary analysis, a third of all patients reported chronic clinically relevant pain associated with the ICU stay 6 months after ICU discharge. Half of these patients experienced chronic pain conditions before ICU admission and reported additional sources of pain. Most important, 16% of all patients had no preexisting pain condition and now experience chronic ICU-related pain. The majority of patients with chronic ICU-related pain reported a high degree of disabling pain, limiting daily activities.

Conclusions:
A high percentage of former ICU patients develop chronic pain conditions associated with critical care. These patients differ significantly from control data in terms of pain intensity and show high levels of interference with pain. The presence of sepsis per se seems to play a marginal role for the development of chronic ICU-related pain.
Demodex Folliculitis of the Scalp: Clinicopathological Study of an Uncommon Entity
Authors: Helou Wissam , Avitan-Hersh Emily , Bergman Reuven 
Published: March 2016

Abstract:
Demodex is a saprophytic mite in humans commonly present in the pilosebaceous units, which has been implicated as a pathogen in several skin conditions. The clinical presentation and histopathology of Demodex folliculitis of the scalp have been described in only a few case reports. This study was performed to further elucidate the clinicopathological features of this entity. We have studied 333 consecutively submitted scalp biopsies performed for hair loss and alopecia. All specimens were completely step-sectioned. Biopsies with Demodex mites were further studied histopathologically, and the patients' clinical files were reviewed. There were 17 biopsies (5.1%) with Demodex in at least 1 pilosebaceous unit. Based on the clinical presentation, histopathology, and response to therapy, Demodex was considered to be nonpathogenic in 13 cases. The remaining 4 cases were characterized by hair loss, scalp erythema, scales, and pustules. There were 2 or more pilosebaceous units with Demodex along mononuclear and/or neutrophilic infiltrates around and in the involved follicles and occasionally granulomas. All 4 cases responded completely to metronidazole therapy. In conclusion, Demodex is infrequently found in scalp biopsies for hair loss and alopecia, and, in most cases, it does not seem to be pathogenic. Occasionally, however, it is associated with folliculitis characterized by hair loss, erythema, scales, and pustules clinically; neutrophilic and/or mononuclear-cell folliculitis with occasional granulomas histopathologically; and a prompt response to anti-Demodex therapy.
Strategic Moments
Authors: Fletcher Susan Marilyn , McBurney Helen 
Published: March 2016

PURPOSE:
There has been extensive investigation of attendance rates at cardiac rehabilitation (CR) but little attention to client reasoning around attendance. This study explored decision-making drivers for attendance or nonattendance at CR programs in rural Victoria, Australia.

METHODS:
All new patients referred to the CR programs at either the local hospital or community health service over a 6-month period were invited to participate and were interviewed before, after, and at 6 months post-CR. Content analysis was used to identify and group common themes that emerged from the semistructured interviews.

RESULTS:
Eighty-four of the 114 patients referred agreed to participate in the study. Multiple barriers or facilitators affected the decisions of all clients. Three themes were identified that reflected the participant decision-making experience: (1) invitation and information about participation in CR; (2) person-centered approach to CR provision; and (3) ongoing support needs. Significant decision-making points identified were after the cardiac event; before and after hospital-based CR; before and after community-based CR; and at 6 months after the cardiac event. At any time there is a risk that the client can become lost or disengaged in the service system, but providing contact at these points can allow them to reengage.

CONCLUSIONS:
This study provided the opportunity to hear participant voices, describing their decisions around CR attendance after a cardiac event. They highlighted the complexity of issues confronting them and suggested improvements to optimize their attendance and to maintain lifestyle changes.