bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential of activated microglia as a source of dysregulated extracellular microRNAs contributing to neurodegeneration in amyotrophic lateral sclerosis
Authors: Christoforidou Eleni , Joilin Greig , Hafezparast Majid 
Published: April 2020

AbstractAmyotrophic lateral sclerosis (ALS) is the most common form of motor neuron degeneration in adults, and several mechanisms underlying the disease pathology have been proposed. It has been shown that glia communicate with other cells by releasing extracellular vesicles containing proteins and nucleic acids, including microRNAs (miRNAs), which play a role in the post-transcriptional regulation of gene expression. Dysregulation of miRNAs is commonly observed in ALS patients, together with inflammation and an altered microglial phenotype. However, the role of miRNA-containing vesicles in microglia-to-neuron communication in the context of ALS has not been explored in depth. This review summarises the evidence for the presence of inflammation, pro-inflammatory microglia and dysregulated miRNAs in ALS, then explores how microglia may potentially be responsible for this miRNA dysregulation. The possibility of pro-inflammatory ALS microglia releasing miRNAs which may then enter neuronal cells to contribute to degeneration is also explored. Based on the literature reviewed here, microglia are a likely source of dysregulated miRNAs and potential mediators of neurodegenerative processes. Therefore, dysregulated miRNAs may be promising candidates for the development of therapeutic strategies.
Online compensation detecting for real-time reduction of compensatory motions during reaching: a pilot study with stroke survivors
Authors: Cai Siqi , Wei Xuyang , Su Enze , Wu Weifeng , Zheng Haiqing , Xie Longhan 
Published: April 2020

Abstract
Background
Compensations are commonly observed in patients with stroke when they engage in reaching without supervision; these behaviors may be detrimental to long-term functional improvement. Automatic detection and reduction of compensation cab help patients perform tasks correctly and promote better upper extremity recovery.

Objective
Our first objective is to verify the feasibility of detecting compensation online using machine learning methods and pressure distribution data. Second objective was to investigate whether compensations of stroke survivors can be reduced by audiovisual or force feedback. The third objective was to compare the effectiveness of audiovisual and force feedback in reducing compensation.

Methods
Eight patients with stroke performed reaching tasks while pressure distribution data were recorded. Both the offline and online recognition accuracy were investigated to assess the feasibility of applying a support vector machine (SVM) based compensation detection system. During reduction of compensation, audiovisual feedback was delivered using virtual reality technology, and force feedback was delivered through a rehabilitation robot.

Results
Good classification performance was obtained in online compensation recognition, with an average F1-score of over 0.95. Based on accurate online detection, real-time feedback significantly decreased compensations of patients with stroke in comparison with no-feedback condition (p < 0.001). Meanwhile, the difference between audiovisual and force feedback was also significant (p < 0.001) and force feedback was more effective in reducing compensation in patients with stroke.

Conclusions
Accurate online recognition validated the feasibility of monitoring compensations using machine learning algorithms and pressure distribution data. Reliable online detection also paved the way for reducing compensations by providing feedback to patients with stroke. Our findings suggested that real-time feedback could be an effective approach to reducing compensatory patterns and force feedback demonstrated a more enviable potential compared with audiovisual feedback.
The efficacy of positioning stents in preventing Oral complications after head and neck radiotherapy: a systematic literature review
Authors: Chen Dong , Chen Xiaoju , Chen Xinmei , Jiang Nanchuan , Jiang Li 
Published: April 2020

Abstract
Background
Positioning stent in head and neck radiotherapy seems to have benefit to prevent oral complications but it hasn’t been summarized by an evidence-based method.

Objectives
This review aims to evaluate the efficacy of positioning stents in preventing oral complications after radiotherapy.

Methods
We conducted an electronic search in MEDLINE, EMBASE, Cochrane CDSR, and Cochrane CENTRAL database for randomized-controlled clinical trials, controlled clinical trials and cohort studies that assessed oral complications after head and neck radiotherapy with positioning stents. Two reviewers extracted information on radiotherapy, follow-up period, oral complications and assessments independently.

Results
Three RCTs and two cohort studies were included in this review. Oral complications such as mucositis, xerostomia, taste alteration, trismus, salivary changes, dysphagia and pain on swallowing were assessed by different methods in these studies.

Conclusions
Oral complications were common in patients after head and neck radiotherapy. There is insufficient evidence that positioning stents have a preventive effect against xerostomia, and it needs more high-quality and prospective trials with long-term follow-up to support it.
A scoping review and proposed workflow for multi-omic rare disease research
Authors: Kerr Katie , McAneney Helen , Smyth Laura J. , Bailie Caitlin , McKee Shane , McKnight Amy Jayne 
Published: April 2020

Abstract
Background
Patients with rare diseases face unique challenges in obtaining a diagnosis, appropriate medical care and access to support services. Whole genome and exome sequencing have increased identification of causal variants compared to single gene testing alone, with diagnostic rates of approximately 50% for inherited diseases, however integrated multi-omic analysis may further increase diagnostic yield. Additionally, multi-omic analysis can aid the explanation of genotypic and phenotypic heterogeneity, which may not be evident from single omic analyses.

Main body
This scoping review took a systematic approach to comprehensively search the electronic databases MEDLINE, EMBASE, PubMed, Web of Science, Scopus, Google Scholar, and the grey literature databases OpenGrey / GreyLit for journal articles pertaining to multi-omics and rare disease, written in English and published prior to the 30th December 2018. Additionally, The Cancer Genome Atlas publications were searched for relevant studies and forward citation searching / screening of reference lists was performed to identify further eligible articles. Following title, abstract and full text screening, 66 articles were found to be eligible for inclusion in this review. Of these 42 (64%) were studies of multi-omics and rare cancer, two (3%) were studies of multi-omics and a pre-cancerous condition, and 22 (33.3%) were studies of non-cancerous rare diseases. The average age of participants (where known) across studies was 39.4 years. There has been a significant increase in the number of multi-omic studies in recent years, with 66.7% of included studies conducted since 2016 and 33% since 2018. Fourteen combinations of multi-omic analyses for rare disease research were returned spanning genomics, epigenomics, transcriptomics, proteomics, phenomics and metabolomics.

Conclusions
This scoping review emphasises the value of multi-omic analysis for rare disease research in several ways compared to single omic analysis, ranging from the provision of a diagnosis, identification of prognostic biomarkers, distinct molecular subtypes (particularly for rare cancers), and identification of novel therapeutic targets. Moving forward there is a critical need for collaboration of multi-omic rare disease studies to increase the potential to generate robust outcomes and development of standardised biorepository collection and reporting structures for multi-omic studies.
Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial
Authors: Düring Joachim , Annborn Martin , Cronberg Tobias , Dankiewicz Josef , Devaux Yvan , Hassager Christian , Horn Janneke , Kjaergaard Jesper , Kuiper Michael , Nikoukhah Homa Rafi , Stammet Pascal , Undén Johan , Wanscher Michael Jaeger , Wise Matt , Friberg Hans , Nielsen Niklas 
Published: April 2020

Abstract
Background
Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest.

Methods
Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score.

Results
Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12–0.27], p < 0.001.

Conclusion
Copeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure.

Trial registration
Clinical Trials, NCT01020916. Registered November 26, 2009.
CCMetagen: comprehensive and accurate identification of eukaryotes and prokaryotes in metagenomic data
Authors: Marcelino Vanessa R. , Clausen Philip T. L. C. , Buchmann Jan P. , Wille Michelle , Iredell Jonathan R. , Meyer Wieland , Lund Ole , Sorrell Tania C. , Holmes Edward C. 
Published: April 2020

AbstractThere is an increasing demand for accurate and fast metagenome classifiers that can not only identify bacteria, but all members of a microbial community. We used a recently developed concept in read mapping to develop a highly accurate metagenomic classification pipeline named CCMetagen. The pipeline substantially outperforms other commonly used software in identifying bacteria and fungi and can efficiently use the entire NCBI nucleotide collection as a reference to detect species with incomplete genome data from all biological kingdoms. CCMetagen is user-friendly, and the results can be easily integrated into microbial community analysis software for streamlined and automated microbiome studies.
Effect of nutritional interventions on discharged older patients: study protocol for a randomized controlled trial
Authors: Munk Tina , Svendsen Jonas Anias , Knudsen Anne Wilkens , Østergaard Tanja Bak , Beck Anne Marie 
Published: April 2020

Abstract
Background
During hospitalization, many older patients are at nutritional risk or malnourished, and their nutritional condition is often further impaired during hospitalization. After discharge, a “nutrition gap” often occurs in which the patient does not receive enough nutrition to ensure an optimal recovery.

Methods
The study is a randomized controlled study ongoing over 112 days. At discharge, the intervention group receives guidance from a clinical dietitian, and an individualized nutrition plan is made. The dietitian will perform telephone follow-up after 4 and 30 days. It will also be possible for the participant, the participant’s relatives, or the participant’s municipality to contact the dietitian if nutritional questions arise. At the time of discharge, the intervention group will receive a package containing foods and drinks that will cover their nutritional needs on the first day after discharge. They will also receive a goodie bag containing samples of protein-rich, milk-based drinks. Data are collected on quality of life, appetite, physical function, dietary intake, weight, height, energy and protein needs, and experience of discharge and cooperation with the municipality. Information about nutrition status will be sent to the municipality so that the municipality can take over nutritional treatment. The control group receives a standard treatment.

Discussion
This study is the first to combine previously successful single nutritional interventions into a multimodal intervention whose aim is to obtain an effect on patient-related outcomes. We hope that the results will prove beneficial and help to ensure the cross-sector quality of nutritional support to older patients.

Trial registration
ClinicalTrials.gov, NCT03488329. April 5, 2018.
Peer support during in vivo exposure homework to reverse attrition from prolonged exposure therapy for posttraumatic stress disorder (PTSD): description of a randomized controlled trial
Authors: Hernandez-Tejada Melba A. , Muzzy Wendy , Price Matthew , Hamski Stephanie , Hart Stephanie , Foa Edna , Acierno Ron 
Published: April 2020

Abstract
Background
Effective treatments for posttraumatic stress disorder (PTSD) (e.g., prolonged exposure (PE); cognitive processing therapy (CPT)) exist and are widely adopted by the Departments of Veterans Affairs (VA) and Defense (DoD). Unfortunately, dropout from these treatments regularly exceeds 30%. However, in a recent survey of patients who dropped out of PE, approximately half indicated a greater likelihood of completion if a peer who had completed treatment were available to help with the in vivo exposure homework.

Methods
We will use a between-groups randomized controlled design with repeated assessment at baseline, post treatment, and 3- and 6-month follow-up across measures of PTSD, depression, and functioning with 150 veterans who have indicated that they intend to drop out of treatment. Participants will be randomly assigned to one of two PE + Peer Support conditions: (1) a peer will offer support directly during in vivo exposure homework for 3–4 weeks; vs (2) a peer will call weekly for 3–4 weeks to offer general support and to check in on treatment progress.

Discussion
The present study was designed to test the hypothesis that dropout from exposure-based PTSD treatment may be mitigated by using peers as support agents directly during PE in vivo homework experiences. Specifically, we intend to determine: whether patients who have dropped out of PE and are offered the “in vivo peer” adjunctive component to PE therapy will (1) return and complete treatment and (2) evince reduced PTSD symptomatology, compared to the same PE treatment, but with general peer support more reflective of current VA practices.

Trial registration
This study protocol is approved and information is available at ClinicalTrials.gov, ID: NCT03485391. Registered on 2 April 2018.
Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues
Authors: Larouche Jean-David , Trofimov Assya , Hesnard Leslie , Ehx Gregory , Zhao Qingchuan , Vincent Krystel , Durette Chantal , Gendron Patrick , Laverdure Jean-Philippe , Bonneil Éric , Côté Caroline , Lemieux Sébastien , Thibault Pierre , Perreault Claude 
Published: April 2020

Abstract
Background
Endogenous retroelements (EREs) constitute about 42% of the human genome and have been implicated in common human diseases such as autoimmunity and cancer. The dominant paradigm holds that EREs are expressed in embryonic stem cells (ESCs) and germline cells but are repressed in differentiated somatic cells. Despite evidence that some EREs can be expressed at the RNA and protein levels in specific contexts, a system-level evaluation of their expression in human tissues is lacking.

Methods
Using RNA sequencing data, we analyzed ERE expression in 32 human tissues and cell types, including medullary thymic epithelial cells (mTECs). A tissue specificity index was computed to identify tissue-restricted ERE families. We also analyzed the transcriptome of mTECs in wild-type and autoimmune regulator (AIRE)-deficient mice. Finally, we developed a proteogenomic workflow combining RNA sequencing and mass spectrometry (MS) in order to evaluate whether EREs might be translated and generate MHC I-associated peptides (MAP) in B-lymphoblastoid cell lines (B-LCL) from 16 individuals.

Results
We report that all human tissues express EREs, but the breadth and magnitude of ERE expression are very heterogeneous from one tissue to another. ERE expression was particularly high in two MHC I-deficient tissues (ESCs and testis) and one MHC I-expressing tissue, mTECs. In mutant mice, we report that the exceptional expression of EREs in mTECs was AIRE-independent. MS analyses identified 103 non-redundant ERE-derived MAPs (ereMAPs) in B-LCLs. These ereMAPs preferentially derived from sense translation of intronic EREs. Notably, detailed analyses of their amino acid composition revealed that ERE-derived MAPs presented homology to viral MAPs.

Conclusions
This study shows that ERE expression in somatic tissues is more pervasive and heterogeneous than anticipated. The high and diversified expression of EREs in mTECs and their ability to generate MAPs suggest that EREs may play an important role in the establishment of self-tolerance. The viral-like properties of ERE-derived MAPs suggest that those not expressed in mTECs can be highly immunogenic.
Tapering of biological antirheumatic drugs in rheumatoid arthritis patients is achievable and cost-effective in daily clinical practice: data from the Brussels UCLouvain RA Cohort
Authors: Dierckx Stéphanie , Sokolova Tatiana , Lauwerys Bernard R. , Avramovska Aleksandra , de Bellefon Laurent Meric , Toukap Adrien Nzeusseu , Stoenoiu Maria , Houssiau Frédéric A. , Durez Patrick 
Published: April 2020

Abstract
Background/purpose
Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings.

Results
Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost.

Conclusion
In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts.

Trial registration
This retrospective non-interventional study was retrospectively registered with local ethics approval.
Blended learning of radiology improves medical students’ performance, satisfaction, and engagement
Authors: Vavasseur Adrien , Muscari Fabrice , Meyrignac Olivier , Nodot Matthieu , Dedouit Fabrice , Revel-Mouroz Paul , Dercle Louis , Rozenblum Laura , Wang Lucy , Maulat Charlotte , Rousseau Hervé , Otal Philippe , Dercle Laurent , Mokrane Fatima-Zohra 
Published: April 2020

Abstract
Purpose
To evaluate the impact of blended learning using a combination of educational resources (flipped classroom and short videos) on medical students’ (MSs) for radiology learning.

Material and methods
A cohort of 353 MSs from 2015 to 2018 was prospectively evaluated. MSs were assigned to four groups (high, high-intermediate, low-intermediate, and low achievers) based on their results to a 20-MCQs performance evaluation referred to as the pretest. MSs had then free access to a self-paced course totalizing 61 videos based on abdominal imaging over a period of 3 months. Performance was evaluated using the change between posttest (the same 20 MCQs as pretest) and pretest results. Satisfaction was measured using a satisfaction survey with directed and spontaneous feedbacks. Engagement was graded according to audience retention and attendance on a web content management system.

Results
Performance change between pre and posttest was significantly different between the four categories (ANOVA, P = 10−9): low pretest achievers demonstrated the highest improvement (mean ± SD, + 11.3 ± 22.8 points) while high pretest achievers showed a decrease in their posttest score (mean ± SD, − 3.6 ± 19 points). Directed feedback collected from 73.3% of participants showed a 99% of overall satisfaction. Spontaneous feedback showed that the concept of “pleasure in learning” was the most cited advantage, followed by “flexibility.” Engagement increased over years and the number of views increased of 2.47-fold in 2 years.

Conclusion
Learning formats including new pedagogical concepts as blended learning, and current technologies allow improvement in medical student’s performance, satisfaction, and engagement.
Diagnosis and management of respiratory viruses in critically ill adult patients: an international survey of knowledge and practice among intensivists
Authors: Philippot Quentin , Labbé Vincent , Pichon Jérémie , Djibré Michel , Fartoukh Muriel , Voiriot Guillaume 
Published: April 2020

AbstractIn this survey endorsed by the European Society of Intensive Care Medicine (ESICM), we aimed to describe the practice patterns of intensivists worldwide, regarding their diagnosis and management of respiratory viruses in lower respiratory tract infections. There were 229 respondents from 53 countries, mainly in Europe (78%). Our main findings are that a majority of intensivists (i) searched for respiratory viruses in case of severe community-acquired LRTI in adults, whatever the season and the medical history and clinical presentation; (ii) had access to large-panel respiratory mPCR; (iii) used them as first-line diagnostic test in routine practice; (iv) had some knowledge about the panel of the mPCR that they use, but markedly less about the cost. However, we observed strong heterogeneity regarding how intensivists took into account mPCR results for infection control (confinement measures) and patient care (antiviral treatment and antibiotics management).