bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial direct current stimulation (tDCS) for improving aphasia after stroke: a systematic review with network meta-analysis of randomized controlled trials
Authors: Elsner Bernhard , Kugler Joachim , Mehrholz Jan 
Published: July 2020

Summary
Background
Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving aphasia after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types.

Methods
This is a systematic review of randomized controlled trials with network meta-analysis (NMA). We searched the following databases until 4 February 2020: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of functional communication, versus control, after stroke. PROSPERO ID: CRD42019135696.

Results
We included 25 studies with 471 participants. Our NMA showed that tDCS did not improve our primary outcome, that of functional communication. There was evidence of an effect of anodal tDCS, particularly over the left inferior frontal gyrus, in improving our secondary outcome, that of performance in naming nouns (SMD = 0.51; 95% CI 0.11 to 0.90). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events.

Conclusion
Comparing different application/protocols of tDCS shows that the anodal application, particularly over the left inferior frontal gyrus, seems to be the most promising tDCS treatment option to improve performance in naming in people with stroke.
Longitudinal transcriptomic characterization of viral genes in HSV-1 infected tree shrew trigeminal ganglia
Authors: Wang Erlin , Ye Yunshuang , Zhang Ke , Yang Jinlong , Gong Daohua , Zhang Jianhua , Hong Renjun , Zhang Huan , Li Lihong , Chen Guijun , Yang Liping , Liu Jianmei , Cao Hanyu , Du Ting , Fraser Nigel W. , Cheng Le , Cao Xia , Zhou Jumin 
Published: July 2020

Abstract
Background
Following acute infection, Herpes Simplex virus-1 (HSV-1) establishes lifelong latency and recurrent reactivation in the sensory neurons of trigeminal ganglia (TG). Infected tree shrew differs from mouse and show characteristics similar to human infection. A detailed transcriptomic analysis of the tree shrew model could provide mechanistic insights into HSV-1 infection in humans.

Methods
We sequenced the transcriptome of infected TGs from tree shrews and mice, and 4 human donors, then examined viral genes expression up to 58 days in infected TGs from mouse and tree shrew, and compare the latency data with that in human TGs.

Results
Here, we found that all HSV-1 genes could be detected in mouse TGs during acute infection, but 22 viral genes necessary for viral transcription, replication and viral maturation were not expressed in tree shrew TGs during this stage. Importantly, during latency, we found that LAT could be detected both in mouse and tree shrew, but the latter also has an ICP0 transcript signal absent in mouse but present in human samples. Importantly, we observed that infected human and tree shrew TGs have a more similar LAT region transcription peak. More importantly, we observed that HSV-1 spontaneously reactivates from latently infected tree shrews with relatively high efficiency.

Conclusions
These results represent the first longitudinal transcriptomic characterization of HSV-1 infection in during acute, latency and recurrent phases, and revealed that tree shrew infection has important similar features with human infection.
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis
Authors: Coelho Teresa , Adams David , Conceição Isabel , Waddington-Cruz Márcia , Schmidt Hartmut H. , Buades Juan , Campistol Josep , Berk John L. , Polydefkis Michael , Wang Jing Jing , Chen Jihong , Sweetser Marianne T. , Gollob Jared , Suhr Ole B. 
Published: July 2020

AbstractBackgroundPatisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis.In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup.ResultsTwenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (~ 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran’s impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months.ConclusionsLong-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis.Trial registrationThe study was registered atClinicalTrials.gov(identifier:NCT01961921) on October 14, 2013.
Exome sequencing for diagnosis of congenital hemolytic anemia
Authors: Mansour-Hendili Lamisse , Aissat Abdelrazak , Badaoui Bouchra , Sakka Mehdi , Gameiro Christine , Ortonne Valérie , Wagner-Ballon Orianne , Pissard Serge , Picard Véronique , Ghazal Khaldoun , Bahuau Michel , Guitton Corinne , Mansour Ziad , Duplan Mylène , Petit Arnaud , Costedoat-Chalumeau Nathalie , Michel Marc , Bartolucci Pablo , Moutereau Stéphane , Funalot Benoît , Galactéros Frédéric 
Published: July 2020

Abstract
Background
Congenital hemolytic anemia constitutes a heterogeneous group of rare genetic disorders of red blood cells. Diagnosis is based on clinical data, family history and phenotypic testing, genetic analyses being usually performed as a late step. In this study, we explored 40 patients with congenital hemolytic anemia by whole exome sequencing: 20 patients with hereditary spherocytosis and 20 patients with unexplained hemolysis.

Results
A probable genetic cause of disease was identified in 82.5% of the patients (33/40): 100% of those with suspected hereditary spherocytosis (20/20) and 65% of those with unexplained hemolysis (13/20). We found that several patients carried genetic variations in more than one gene (3/20 in the hereditary spherocytosis group, 6/13 fully elucidated patients in the unexplained hemolysis group), giving a more accurate picture of the genetic complexity of congenital hemolytic anemia. In addition, whole exome sequencing allowed us to identify genetic variants in non-congenital hemolytic anemia genes that explained part of the phenotype in 3 patients.

Conclusion
The rapid development of next generation sequencing has rendered the genetic study of these diseases much easier and cheaper. Whole exome sequencing in congenital hemolytic anemia could provide a more precise and quicker diagnosis, improve patients’ healthcare and probably has to be democratized notably for complex cases.
Merging microarray studies to identify a common gene expression signature to several structural heart diseases
Authors: Fajarda Olga , Duarte-Pereira Sara , Silva Raquel M. , Oliveira José Luís 
Published: July 2020

AbstractBackgroundHeart disease is the leading cause of death worldwide. Knowing a gene expression signature in heart disease can lead to the development of more efficient diagnosis and treatments that may prevent premature deaths. A large amount of microarray data is available in public repositories and can be used to identify differentially expressed genes. However, most of the microarray datasets are composed of a reduced number of samples and to obtain more reliable results, several datasets have to be merged, which is a challenging task. The identification of differentially expressed genes is commonly done using statistical methods. Nonetheless, these methods are based on the definition of an arbitrary threshold to select the differentially expressed genes and there is no consensus on the values that should be used.ResultsNine publicly available microarray datasets from studies of different heart diseases were merged to form a dataset composed of 689 samples and 8354 features. Subsequently, the adjustedp-value and fold change were determined and by combining a set of adjustedp-values cutoffs with a list of different fold change thresholds, 12 sets of differentially expressed genes were obtained. To select the set of differentially expressed genes that has the best accuracy in classifying samples from patients with heart diseases and samples from patients with no heart condition, the random forest algorithm was used. A set of 62 differentially expressed genes having a classification accuracy of approximately 95% was identified.ConclusionsWe identified a gene expression signature common to different cardiac diseases and supported our findings by showing their involvement in the pathophysiology of the heart. The approach used in this study is suitable for the identification of gene expression signatures, and can be extended to different diseases.
Prone positioning in severe ARDS requiring extracorporeal membrane oxygenation
Authors: Rilinger Jonathan , Zotzmann Viviane , Bemtgen Xavier , Schumacher Carin , Biever Paul M. , Duerschmied Daniel , Kaier Klaus , Stachon Peter , von zur Mühlen Constantin , Zehender Manfred , Bode Christoph , Staudacher Dawid L. , Wengenmayer Tobias 
Published: July 2020

Abstract
Background
Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support.

Methods
We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching.

Results
A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden’s Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02).

Conclusion
In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.
Outcome reporting recommendations for clinical trial protocols and reports: a scoping review
Authors: Butcher Nancy J. , Mew Emma J. , Monsour Andrea , Chan An-Wen , Moher David , Offringa Martin 
Published: July 2020

Abstract
Background
Clinicians, patients, and policy-makers rely on published evidence from clinical trials to help inform decision-making. A lack of complete and transparent reporting of the investigated trial outcomes limits reproducibility of results and knowledge synthesis efforts, and contributes to outcome switching and other reporting biases. Outcome-specific extensions for the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT-Outcomes) and Consolidated Standards of Reporting Trials (CONSORT-Outcomes) reporting guidelines are under development to facilitate harmonized reporting of outcomes in trial protocols and reports. The aim of this review was to identify and synthesize existing guidance for trial outcome reporting to inform extension development.

Methods
We searched for documents published in the last 10 years that provided guidance on trial outcome reporting using: an electronic bibliographic database search (MEDLINE and the Cochrane Methodology Register); a grey literature search; and solicitation of colleagues using a snowballing approach. Two reviewers completed title and abstract screening, full-text screening, and data charting after training. Extracted trial outcome reporting guidance was compared with candidate reporting items to support, refute, or refine the items and to assess the need for the development of additional items.

Results
In total, 1758 trial outcome reporting recommendations were identified within 244 eligible documents. The majority of documents were published by academic journals (72%). Comparison of each recommendation with the initial list of 70 candidate items led to the development of an additional 62 items, producing 132 candidate items. The items encompassed outcome selection, definition, measurement, analysis, interpretation, and reporting of modifications between trial documents. The total number of documents supporting each candidate item ranged widely (median 5, range 0–84 documents per item), illustrating heterogeneity in the recommendations currently available for outcome reporting across a large and diverse sample of sources.

Conclusions
Outcome reporting guidance for clinical trial protocols and reports lacks consistency and is spread across a large number of sources that may be challenging to access and implement in practice. Evidence and consensus-based guidance, currently in development (SPIRIT-Outcomes and CONSORT-Outcomes), may help authors adequately describe trial outcomes in protocols and reports transparently and completely to help reduce avoidable research waste.
Efficacy of chloroquine versus lopinavir/ritonavir in mild/general COVID-19 infection: a prospective, open-label, multicenter, randomized controlled clinical study
Authors: Liu Xi , Chen Huili , Shang Yuqi , Zhu Hongqiong , Chen Gongqi , Chen Yuanli , Liu Shaoxuan , Zhou Yaoyong , Huang Mingxing , Hong Zhongsi , Xia Jinyu 
Published: July 2020

Abstract
Background
The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment has yet been confirmed. The adage “old drug, new trick” in this context may suggest the important therapeutic potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals. Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir.

Methods/design
This is a prospective, open-label, randomized controlled, multicenter clinical study. The study consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-sided tests with a statistical significance level of 5%.

Discussion
This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity and is safe, it could be tested as a future COVID-19 treatment.

Trial registration
Chinese Clinical Trial Registry, ID: ChiCTR2000029741. Registered on 11 February 2020.
Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis
Authors: Wickel Jonathan , Chung Ha-Yeun , Platzer Stephanie , Lehmann Thomas , Prüss Harald , Leypoldt Frank , Günther Albrecht , Scherag André , Geis Christian ,   on behalf of the GENERATE Study Group
Published: July 2020

Abstract
Background
Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.

Methods
Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.

Discussion
The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.

Trial registration
Clinicaltrials.gov, NCT03993262. Registered June 20, 2019;
German Clinical Trials Register, DRKS00017497.
Impacts of chest compression cycle length and real-time feedback with a CPRmeter® on chest compression quality in out-of-hospital cardiac arrest: study protocol for a multicenter randomized controlled factorial plan trial
Authors: Buléon Clément , Parienti Jean-Jacques , Morilland-Lecoq Elodie , Halbout Laurent , Cesaréo Eric , Dubien Pierre-Yves , Jardel Benoit , Boyer Christophe , Husson Kévin , Andriamirado Florian , Benet Xavier , Morel-Marechal Emmanuel , Aubrion Antoine , Muntean Catalin , Dupire Erwan , Roupie Eric , Hubert Hervé , Vilhelm Christian , Gueugniaud Pierre-Yves ,   on behalf of the CILICA-HS study group
Published: July 2020

Abstract
Background
With a survival rate of 6 to 11%, out-of-hospital cardiac arrest (OHCA) remains a healthcare challenge with room for improvement in morbidity and mortality. The guidelines emphasize the highest possible quality of cardiopulmonary resuscitation (CPR) and chest compressions (CC). It is essential to minimize CC interruptions, and therefore increase the chest compression fraction (CCF), as this is an independent factor for survival. Survival is significantly and positively correlated with the suitability of CCF targets, CC frequency, CC depth, and brief predefibrillation pause. CC guidance improves adherence to recommendations and allows closer alignment with the CC objectives. The possibility of improving CCF by lengthening the time between two CC relays and the effect of real-time feedback on the quality of the CC must be investigated.

Methods
Using a 2 × 2 factorial design in a multicenter randomized trial, two hypotheses will be tested simultaneously: (i) a 4-min relay rhythm improves the CCF (reducing the no-flow time) compared to the currently recommended 2-min relay rate, and (ii) a guiding tool improves the quality of CC. Primary outcomes (i) CCF and (ii) correct compression score will be recorded by a real-time feedback device. Five hundred adult nontraumatic OHCAs will be included over 2 years. Patients will be randomized in a 1:1:1:1 distribution receiving advanced CPR as follows: 2-min blind, 2 min with guidance, 4-min blind, or 4 min with guidance. Secondary outcomes are the depth, frequency, and release of CC; length (care, no-flow, and low-flow); rate of return of spontaneous circulation; characteristics of advanced CPR; survival at hospital admission; survival and neurological state on days 1 and 30 (or intensive care discharge); and dosage of neuron-specific enolase on days 1 and 3.

Discussion
This study will contribute to assessing the impact of real-time feedback on CC quality in practical conditions of OHCA resuscitation. It will also provide insight into the feasibility of extending the relay rhythm between two rescuers from the currently recommended 2 to 4 min.

Trial registration
ClinicalTrials.gov, NCT03817892. Registered on 28 January 2019