bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: study protocol of a randomized multi-center phase III trial—AkniPro 2
Authors: Scheller Christian , Strauss Christian , Leisz Sandra , Hänel Pia , Klemm Ariane , Kowoll Simone , Böselt Iris , Rahne Torsten , Wienke Andreas 
Published: July 2021

Abstract
Background
A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18–1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery.

Methods
This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I–IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1–3) are assigned to either the therapy (intravenous nimodipine 1–2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1–3 versus GR 4–5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed.

Discussion
Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient’s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research.

Trial registration
EudraCT 2019-002317-19, DRKS00019107. 8th May 2020.
Baidu Jieduan granules, traditional Chinese medicine, in the treatment of moderate coronavirus disease-2019 (COVID-19): study protocol for an open-label, randomized controlled clinical trial
Authors: Zhang Wen , Xie Qin , Xu Xiaoming , Sun Shuting , Fan Tian , Wu Xinxin , Qu Yao , Che Jinhua , Huang Tingrong , Li Huacheng , Zheng You , Jiang Chao , Fang Bangjiang , Zhou Shuang 
Published: July 2021

Abstract
Background
Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19.

Methods/design
This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial.

Discussion
The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19.

Trial registration
Chinese Clinical Trial Registry ChiCTR2000029869. Registered on 15 February 2020
Effects of real-time feedback during decline walking on kinematic and kinetic gait parameters in a healthy population: study protocol for a randomized trial — up and down
Authors: Widhalm Klaus , Durstberger Sebastian , Putz Peter 
Published: July 2021

Abstract
Background
The control of the dynamic functional leg alignment (dFLA) and biomechanical load are important joint-related aspects regarding the development of osteoarthritis (OA). Research on level walking with feedback on load-related parameters has provided innovative treatment possibilities. With regard to walking on sloped surfaces, fundamental biomechanical knowledge exists. However, comprehensive data on the agreement of kinematics and kinetics of self-paced ramp versus sloped treadmill walking is lacking. Further, deeper insights into the control of the dFLA during decline walking and the usefulness of real-time feedback are missing.

Methods/design
Thirty healthy participants aged between 18 and 35 years will be included. They will complete a three-dimensional gait analysis walking self-paced up and down on a 5-m ramp with a 10° inclination. Subsequently, speed-matched to ramp-up walking and self-paced 10° incline split-belt treadmill walking will be assessed. Afterwards, the participants will be observed under four different conditions of 10° declined walking on the same treadmill (a) self-paced walking, (b) self-paced walking with an internal focus of attention, (c) self-paced walking with real-time feedback, and (d) condition c speed-matched walking. The primary outcome parameter will be the frontal knee range of motion (fKROM). Secondary outcomes include the ground reaction force loading rate, spatial-temporal parameters, as well as sagittal, frontal and transversal kinematics, and kinetics for the lower extremities.

Discussion
The findings aim at improving the understanding of the effects of real-time feedback on the control of the dFLA and lower limb loading. Following clinical practicable methods for effective feedback devices can be developed and evaluated. Additionally, the first dataset comparing kinematic and kinetic parameters for decline and incline ramp walking versus walking on an instrumented treadmill will be available for appropriate intervention planning.

Trial registration
ClinicalTrials.govNCT04763850. Prospectively registered on 21 February 2021.
The Core Outcome DEvelopment for Carrier Screening (CODECS) study: protocol for development of a core outcome set
Authors: Richardson Ebony , McEwen Alison , Newton-John Toby , Manera Karine , Jacobs Chris 
Published: July 2021

Abstract
Background
Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for ‘what to measure’ in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention.

Objectives
The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice.

Methods
In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: (i) a systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement; (ii) a systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes; (iii) semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them; (iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps; and (v) a virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting.

Discussion
This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions.

COMET core outcome set registration
http://www.comet-initiative.org/Studies/Details/1381.
The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Authors: Licandro Simonetta Andrea , Crippa Luca , Pomarico Roberta , Perego Raffaella , Fossati Gianluca , Leoni Flavio , Steinkühler Christian 
Published: July 2021

Abstract
Background
In the search of genetic determinants of Duchenne muscular dystrophy (DMD) severity, LTBP4, a member of the latent TGF-β binding protein family, emerged as an important predictor of functional outcome trajectories in mice and humans. Nonsynonymous single-nucleotide polymorphisms in LTBP4 gene associate with prolonged ambulation in DMD patients, whereas an in-frame insertion polymorphism in the mouse LTBP4 locus modulates disease severity in mice by altering proteolytic stability of the Ltbp4 protein and release of transforming growth factor-β (TGF-β). Givinostat, a pan-histone deacetylase inhibitor currently in phase III clinical trials for DMD treatment, significantly reduces fibrosis in muscle tissue and promotes the increase of the cross-sectional area (CSA) of muscles in mdx mice. In this study, we investigated the activity of Givinostat in mdx and in D2.B10 mice, two mouse models expressing different Ltbp4 variants and developing mild or more severe disease as a function of Ltbp4 polymorphism.

Methods
Givinostat and steroids were administrated for 15 weeks in both DMD murine models and their efficacy was evaluated by grip strength and run to exhaustion functional tests. Histological examinations of skeletal muscles were also performed to assess the percentage of fibrotic area and CSA increase.

Results
Givinostat treatment increased maximal normalized strength to levels that were comparable to those of healthy mice in both DMD models. The effect of Givinostat in both grip strength and exhaustion tests was dose-dependent in both strains, and in D2.B10 mice, Givinostat outperformed steroids at its highest dose. The in vivo treatment with Givinostat was effective in improving muscle morphology in both mdx and D2.B10 mice by reducing fibrosis.

Conclusion
Our study provides evidence that Givinostat has a significant effect in ameliorating both muscle function and histological parameters in mdx and D2.B10 murine models suggesting a potential benefit also for patients with a poor prognosis LTBP4 genotype.
N-staging in large cell neuroendocrine carcinoma of the lung: diagnostic value of [18F]FDG PET/CT compared to the histopathology reference standard
Authors: Hautzel Hubertus , Alnajdawi Yazan , Fendler Wolfgang P. , Rischpler Christoph , Darwiche Kaid , Eberhardt Wilfried E. , Umutlu Lale , Theegarten Dirk , Stuschke Martin , Schuler Martin , Aigner Clemens , Herrmann Ken , Plönes Till 
Published: July 2021

Abstract
Background
Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Due to its low differentiation and high glucose transporter 1 (GLUT1) expression, LCNEC demonstrates an increased glucose turnover. Thus, PET/CT with 2-[18F]-fluoro-deoxyglucose ([18F]FDG) is suitable for LCNEC staging. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. This study aimed at evaluating the diagnostic performance of [18F]FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [18F]FDG PET/CT findings.

Methods
Between 03/2014 and 12/2020, 46 patients with LCNEC were included in this single center retrospective analysis. All underwent [18F]FDG PET/CT for pre-operative staging and subsequently either surgery (n = 38) or mediastinoscopy (n = 8). Regarding the lymph node involvement, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for [18F]FDG PET/CT using the final histopathological N-staging (pN0 to pN3) as reference.

Results
Per patient 14 ± 7 (range 4–32) lymph nodes were resected and histologically processed. 31/46 patients had no LCNEC spread into the lymph nodes. In 8/46 patients, the final stage was pN1, in 5/46 pN2 and in 2/46 pN3. [18F]FDG PET/CT diagnosed lymph node metastasis of LCNEC with a sensitivity of 93%, a specificity of 87%, an accuracy of 89%, a PPV of 78% and a NPV of 96%. In the four false positive cases, the [18F]FDG uptake of the lymph nodes was 33 to 67% less in comparison with that of the respective LCNEC primary. Interrater-reliability was high with a strong level of agreement (κ = 0.82).

Conclusions
In LCNEC N-staging with [18F]FDG PET/CT demonstrates both high sensitivity and specificity, an excellent NPV but a slightly reduced PPV. Accordingly, preoperative invasive mediastinal staging may be omitted in cases with cN0 disease by [18F]FDG PET/CT. In [18F]FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [18F]FDG uptake as compared to the LCNEC primary.
Can the cytokine adsorber CytoSorb® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis
Authors: Scharf Christina , Schroeder Ines , Paal Michael , Winkels Martin , Irlbeck Michael , Zoller Michael , Liebchen Uwe 
Published: July 2021

Abstract
Background
A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients.

Methods
Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables.

Results
In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%).

Conclusion
Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.
Trademark infringement recognition assistance system based on human visual Gestalt psychology and trademark design
Authors: Hung Kuo-Ming , Chen Li-Ming , Chen Ting-Wen 
Published: July 2021

AbstractTrademarks are common graphic signs in human society. People used this kind of graphic sign to distinguish the signs of representative significance such as individuals, organizations, countries, and groups. Under effective use, these graphic signs can bring maintenance and development resources and profits to the owner. In addition to maintenance and development, organizations that have obtained resources can further promote national and social progress. However, the benefits of these resources have also attracted the attention of unfair competitors. By imitating counterfeit trademarks that appear, unfair competitors can steal the resources of the original trademark. In order to prevent such acts of unfair competitors, the state has formulated laws to protect trademarks. In the past, there have also been researches on similar trademark searches to assist in trademark protection. Although the original trademark is protected by national laws, unfair competitors have recently used psychological methods to counterfeit the original trademark and steal its resources. Trademarks counterfeited through psychology have the characteristics of confuse consumers and do not constitute infringement under the law. Under the influence of such counterfeit trademarks, the original trademark is still not well protected. In order to effectively prevent such trademark counterfeiting through psychology, this article proposes new features based on trademark design and Gestalt psychology to assist legal judgments. These features correspond to a part of the process that is not fully understood in the human visual system and quantify them. In the experimental results, we used past cases to analyze the proposed assistance system. Discussions based on past judgments proved that the quantitative results of the proposed system are similar to the plaintiff or the judgment to determine the reasons for plagiarism. This result shows that the assistance system proposed in this article can provide visually effective quantitative data, assist the law to prevent malicious plagiarism on images by unfair competitors, and reduce the plagiarism caused by the similar design concepts of late trademark designers.
How do we measure attention? Using factor analysis to establish construct validity of neuropsychological tests
Authors: Treviño Melissa , Zhu Xiaoshu , Lu Yi Yi , Scheuer Luke S. , Passell Eliza , Huang Grace C. , Germine Laura T. , Horowitz Todd S. 
Published: July 2021

AbstractWe investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the “general attention factor”, comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.
Optimizing hospital-to-home transitions for older persons in rural communities: a participatory, multimethod study protocol
Authors: Fox Mary T. , Sidani Souraya , Butler Jeffrey I. , Skinner Mark W. , Macdonald Marilyn , Durocher Evelyne , Hunter Kathleen F. , Wagg Adrian , Weeks Lori E. , MacLeod Ann , Dahlke Sherry 
Published: July 2021

AbstractBackgroundTransitional care involves time-limited interventions focusing on the continuity of care from hospital to home, to optimize patient functioning and management. Providing interventions, as part of transitional care, that optimize the functioning of older people with dementia is critical due to the small window of opportunity in which they can return to their baseline levels of functioning. Yet prior research on transitional care has not included interventions focused on functioning and did not target older people with dementia in rural communities, limiting the applicability of transitional care to this population. Accordingly, the goal of this study is to align hospital-to-home transitional care with the function-related needs of older people with dementia and their family-caregivers in rural communities.MethodsIn this multimethod study, two phases of activities are planned in rural Ontario and Nova Scotia.In phase I, a purposive sample of 15–20 people with dementia and 15–20 family-caregivers in each province will rate the acceptability of six evidence-based interventions and participate in semi-structured interviews to explore the interventions’ acceptability and, where relevant, how to improve their acceptability. Acceptable interventions will be further examined inphase II, in which a purposive sample of healthcare providers, stratified by employment location (hospital vs. homecare) and role (clinician vs. decision-maker), will (1) rate the acceptability of the interventions and (2) participate in semi-structured focus group discussions on the facilitators and barriers to delivering the interventions, and suggestions to enable their incorporation into rural transitional care. Two to three focus groups per stratum (8–10 healthcare providers per focus group) will be held for a total of 8–12 focus groups per province. Data analysis will involve qualitative content analysis of interview and focus group discussions and descriptive statistics of intervention acceptability ratings.DiscussionFindings will (1) include a set of acceptable interventions for rural transitional care that promote older patients’ functioning and family-caregivers’ ability to support patients’ functioning, (2) identify resources needed to incorporate the interventions into rural transitional care, and (3) provide high-quality evidence to inform new transitional care practices and policies and guide future research.