bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatigability in spinal muscular atrophy: validity and reliability of endurance shuttle tests
Authors: Bartels Bart , de Groot Janke F. , Habets Laura E. , Wijngaarde Camiel A. , Vink Wendy , Stam Marloes , Asselman Fay-Lynn , van Eijk Ruben P. A. , van der Pol W. Ludo 
Published: March 2020

Abstract
Background
To determine construct validity and test-retest reliability of Endurance Shuttle Tests as outcome measures for fatigability of remaining motor functions in children and adults with Spinal Muscular Atrophy (SMA) across the severity spectrum.

Results
We assessed the Endurance Shuttle - Nine Hole Peg Test (ESNHPT), − Box and Block Test (ESBBT) and – Walk Test (ESWT) in 61 patients with SMA types 2–4, 25 healthy controls (HC) and 15 disease controls (DC). Convergent validity, discriminative validity and test-retest reliability were investigated. Additionally, we compiled the Endurance Shuttle Combined Score (ESTCS) by selecting the most relevant endurance test of each individual. 54, 70 and 73% of patients with SMA demonstrated increased fatigability on the ESNHPT, ESBBT and the ESWT. Endurance response in SMA was characterized by a decrease in muscle strength, an increase in muscle fatigue and an increase in motor adaptions, thereby confirming convergent validity. Patients with SMA showed increased drop-out rates and a shorter endurance time compared to HC and DC demonstrating good discriminative validity. Test-retest reliability was moderate to excellent (ICC’s ranging from .78 to .91) with a trend towards better performance on retest. The ESTCS increased sample size and drop-out rate up to 100 and 85%.

Conclusions
Fatigability is an important additional dimension of physical impairments across the severity spectrum in children and adults with SMA. The EST’s are reliable and valid to document fatigability of walking, proximal- and distal arm function in SMA and thus are promising outcome measures for use in clinical trials.
Aging-related motor function and dopaminergic neuronal loss in C57BL/6 mice
Authors: Noda Sachiko , Sato Shigeto , Fukuda Takahiro , Tada Norihiro , Hattori Nobutaka 
Published: March 2020

AbstractAging-related dopaminergic neuronal loss and its motor phenotypes are well known. Excessive loss of dopaminergic neurons leads to Parkinson’s disease (PD), the most common neurodegenerative disorder characterized by the loss of nigrostriatal dopamine–producing neurons. In mice, however, aging-related dopaminergic neuronal loss and its consequences for motor function are poorly understood. We observed the phenotype of wild-type C57BL/6 mice over an extended period of time. C57BL/6 mice exhibited age-dependent locomotor impairments, including hindlimb defects and the number of dopaminergic neurons decreased in aged mice, contributing to locomotor dysfunction. We observed a reduction in striatal dopamine levels in aged mice using high-performance liquid chromatography (HPLC). Thus, dopamine levels are affected by the loss of dopaminergic neurons. Furthermore, fragmented mitochondria were observed in dopaminergic neurons of aged mice but not in those of young mice. Aging-related dopaminergic neuronal loss and accumulation of damaged mitochondria may underlie the pathophysiology of aging.
Oncogenic and drug-sensitive RET mutations in human epithelial ovarian cancer
Authors: Guan Luyao , Li Zhang , Xie Feifei , Pang Yuzhi , Zhang Chenyun , Tang Haosha , Zhang Hao , Chen Chun , Zhan Yaying , Zhao Ting , Jiang Hongyuan , Jia Xiaona , Wang Yuexiang , Lu Yuan 
Published: March 2020

AbstractBackgroundEpithelial ovarian cancer (EOC) is a highly lethal malignancy. Improvement in genetic characterization of EOC patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are protein tyrosine kinases (PTKs) whose role in EOC need to be better investigated.MethodsEOC genomic datasets are retrieved and analyzed. The biological and clinical significance ofRETgenomic aberrations in ovarian cancer context are investigated by a series of in vitro and in vivo experiments.ResultsEpithelial ovarian cancer sequencing projects identify recurrent genomicRETmissense mutations in 1.98% of patients, ranking as the top-five hit among the 100 receptor tyrosine kinases-encoding genes. RET mutants R693H and A750T show oncogenic transformation properties in NIH3T3 cells. Introduction of the RET mutants into human EOC cells increases RET signaling, cell viability, anchorage-independent cell growth and tumor xenograft growth in nude mice, demonstrating that they are activating mutations. RET mutants significantly enhance the activation of RET and its downstream MAPK and AKT signaling pathway in ovarian cancer cells. Vandetanib, a clinical approved RET inhibitor, inhibits the cell viability and decreases the activation of RET-MAPK signaling pathways in EOC cells expressing oncogenic RET mutants.ConclusionsThe discovery of RET pathogenic variants in the EOC patients, suggests a previously underestimated role for RET in EOC tumorigenesis. The identification of the gain-of-functionRETmutations in EOC highlights the potential use of RET in targeted therapy to treat ovarian cancer patients.
Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study
Authors: Karbing Dan Stieper , Panigada Mauro , Bottino Nicola , Spinelli Elena , Protti Alessandro , Rees Stephen Edward , Gattinoni Luciano 
Published: March 2020

Abstract
Background
Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS.

Methods
In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample.

Results
Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = − 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch.

Conclusions
The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration.

Trial registration
ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.
Obstacles to detecting isoforms using full-length scRNA-seq data
Authors: Westoby Jennifer , Artemov Pavel , Hemberg Martin , Ferguson-Smith Anne 
Published: March 2020

Abstract
Background
Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk RNA-seq samples. However, these studies generally did not consider the impact of dropouts or isoform quantification errors, potentially confounding the results of these analyses.

Results
In this study, we take a simulation based approach in which we explicitly account for dropouts and isoform quantification errors. We use our simulations to ask to what extent it is possible to study alternative splicing using scRNA-seq. Additionally, we ask what limitations must be overcome to make splicing analysis feasible. We find that the high rate of dropouts associated with scRNA-seq is a major obstacle to studying alternative splicing. In mice and other well-established model organisms, the relatively low rate of isoform quantification errors poses a lesser obstacle to splicing analysis. We find that different models of isoform choice meaningfully change our simulation results.

Conclusions
To accurately study alternative splicing with single-cell RNA-seq, a better understanding of isoform choice and the errors associated with scRNA-seq is required. An increase in the capture efficiency of scRNA-seq would also be beneficial. Until some or all of the above are achieved, we do not recommend attempting to resolve isoforms in individual cells using scRNA-seq.
HiNT: a computational method for detecting copy number variations and translocations from Hi-C data
Authors: Wang Su , Lee Soohyun , Chu Chong , Jain Dhawal , Kerpedjiev Peter , Nelson Geoffrey M. , Walsh Jennifer M. , Alver Burak H. , Park Peter J. 
Published: March 2020

AbstractThe three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield features that can be mistaken for chromosomal interactions. Here, we describe a computational method HiNT (Hi-C for copy Number variation and Translocation detection), which detects copy number variations and interchromosomal translocations within Hi-C data with breakpoints at single base-pair resolution. We demonstrate that HiNT outperforms existing methods on both simulated and real data. We also show that Hi-C can supplement whole-genome sequencing in structure variant detection by locating breakpoints in repetitive regions.
Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial
Authors: Kamata Yohei , Kessoku Takaomi , Shimizu Tomoko , Kobayashi Takashi , Kurihashi Takeo , Sato Satsuki , Kuraji Syotaro , Aoyama Norio , Iwasaki Tomoyuki , Takashiba Shogo , Hamada Nobushiro , Kodama Toshiro , Tamura Toshiyuki , Ino Satoshi , Higurashi Takuma , Taguri Masataka , Yamanaka Takeharu , Yoneda Masato , Usuda Haruki , Wada Koichiro , Nakajima Atsushi , Minabe Masato 
Published: March 2020

Abstract
Background
We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD.

Methods
We will include adult patients (20–85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks.

Discussion
This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD.

Trial registration
University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.
Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort
Authors: Panopoulos S. , Chatzidionysiou Κ. , Tektonidou M. G. , Bournia V. K. , Drosos A. A. , Liossis Stamatis-Nick C. , Dimitroulas T. , Sakkas L. , Boumpas D. , Voulgari P. V. , Daoussis D. , Thomas K. , Georgiopoulos G. , Vosvotekas G. , Garyfallos Α. , Sidiropoulos P. , Bertsias G. , Vassilopoulos D. , Sfikakis P. P. 
Published: March 2020

Abstract
Background
European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc’s optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort.

Methods
Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan–Meier analysis.

Results
Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively.

Conclusions
Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.
Enhancing primary care and preventive services through Interprofessional practice and education
Authors: Fowler Terri , Garr David , Mager Natalie Di Pietro , Stanley Joan 
Published: March 2020

AbstractInterprofessional (IP) practice and education are important when seeking to respond to the growing demand for primary and preventive care services. Multiple professions with synergistic expertise are needed to effectively provide health promotion, disease prevention, and patient education and to help patients with multiple comorbidities, chronic health conditions, and care coordination. A recent study by Schor et al. titled, “Multidisciplinary work promotes preventive medicine and health education in primary care: a cross-sectional survey,” compares the implementation of preventive services in three primary care models. Higher rates of health services, patient education, and health outcomes were documented in two different models of care involving persons in multiple professions when compared with independent solo physicians’ practices. In this commentary, we focus on the value of IP team-based care, continuing professional development, and the impact of the team on practice performance and health outcomes. Key components of effective IP teams include using consistent terminology to describe the team composition and function, team structures with purposeful selection of professions to address gaps in care, leadership support, and IP continuing professional development and education.
Terminal handover in software-defined WLANs
Authors: Chen Zhaohui , Luo Zhaoyang , Duan Xiaohui , Zhang Lianming 
Published: March 2020

AbstractWith the development of wireless LAN (WLAN) technology, wireless access points (APs) are deployed increasingly more and the number of mobile terminals is increasing. It is normal for a mobile terminal to hand over its AP. The traditional terminal handover method cannot effectively control the handover delay and balance the network load due to the inherent drawbacks such as closed encapsulation and the lack of centralized control. In this paper, we introduce the innovative network architecture of software-defined networking (SDN), propose a software-defined WLAN architecture, and propose a seamless handover method and a load balancing handover method of the software-defined WLAN. Experimental results show that the proposed handover method effectively reduces the handover delay, balances the network load, and improves the quality of service (QoS) and resource utilization of the network.
Secondary plant products against Culex pipiens (Linn.), with reference to some changes detected by scanning electron microscope
Authors: Osman Khalid , AL-Emam Ahmed , Moustafa Mahmoud 
Published: March 2020

AbstractTo find environment-friendly and low pest resistance natural mosquitocide, the bio-effects of smokes and oils obtained from leaves of Eucalyptus globulus and Ocimum basilicum against Culex pipiens (Linn.) were investigated. An influence of smokes and oils was tested on the loss ratio of eggs, larvae, pupae, and adult mortality of 1st and 2nd generations of Culex pipiens. Morphological changes of the 2nd generation, including antennae and mouthparts of larvae and adults, were examined by using the scanning electron microscopy (SEM). The smokes of O. basilicum and E. globulus reduced the ratio value of the insect, especially the eggs’ number and adults significantly within 2 generations that lasted 82 days. The impact of O. basilicum smokes on the larval molting and mortality rate was 83.15 and 95.05%, respectively, compared to 29.85 and 82.43 % for E. globulus. The lethal effect of O. basilicum smoke on adults had a loss rate of 100% in both generations than 75.86% by E. globulus. Essential oils from O. basilicum and E. globulus showed a severe and rapid killing effect of C. pipiens within 8 days with a loss ratio of 99.47 and 81.38% of larvae from eggs, respectively. Scanning electron microscopy showed that both smokes could cause prominent malformation to the larval antennae, siphon, and adult mouthparts. In conclusion, either E. globulus or O. basilicum smokes in the long term or either of their oils in the short term could be used as natural repellent agents against Culex pipiens.
Parasitus fimetorum and Macrocheles muscaedomesticae (Acarina:Parasitidae, Macrochelidae) as Natural Predators of the Root Knot Nematode, Meloidogyne javanica Treub
Authors: Heikal Hany Mohamed 
Published: March 2020

AbstractThe potential use of two predacious mites,Parasitus fimetorum(Berlese 1904) andMacrocheles muscaedomesticae(Scopoli 1972), for controlling the root knot nematode,Meloidogyne javanicaTreub 1885 was evaluated under laboratory and semi-field conditions. Obtained results revealed that the 2 predators significantly reduced the root knot nematode numbers.In addition, the highest reduction percentage (57.24%) in nematode juveniles was recorded at the treatment of (1000 nematode + 10 mites). ForM. muscaedomesticae,the highest mortality percentage (50.83%) in nematode juveniles was recorded at the treatment of (1000 nematode + 50 mites), followed by (1000 nematodes + 20 mites) 48.88%, while the treatment of (1000 nematode + 10 mites) gave (47.13%). The combination of the 2 mite species (1000 nematodes + 50 mites/species) caused the highest mortality percentages in nematode juveniles (69.29%), followed by (1000 nematodes + 20 mite/species) 50.51% and the treatment of (1000 nematode + 10 mite/species) (37.66%). At the pot experiments, the highest overall mortality percentage inM. javanicajuveniles was recorded at the treatment ofP. fimetorum+M. muscaedomesticaegiving (57.07%), followed by the treatment ofP. fimetorum(39.17%), and then, byM. muscaedomesticaealone that recorded only (17.47%). In conclusion, predacious mites can be partially considered a control tool of the parasitic nematodes.
Multimodal intervention program to improve hand hygiene compliance: effectiveness and challenges
Authors: Ben Fredj Sihem , Ben Cheikh Asma , Bhiri Sana , Ghali Hela , Khefacha Salwa , Dhidah Lamine , Merzougui Latifa , Ben Rejeb Mohamed , Said Latiri Houyem 
Published: March 2020

Abstract
Background
Hand hygiene (HH) is considered the most important measure to tackle the transmission of healthcare-associated pathogens. However, compliance with recommendations is usually low and effective improvement strategies are needed. We aimed to assess the effectiveness of an intervention targeting hand hygiene promotion among healthcare workers (HCWs).

Methods
We conducted a pre-post interventional study design in the university hospital Sahloul, Sousse, Tunisia, from January 2015 to December 2016. The intervention program consisted of training sessions and distribution of posters of hand hygiene guidelines. To assess the evolution of HH observance at pre- and post-intervention, the same observation form was distributed and collected at healthcare workers’ workplace.

Results
Of the 1201 and 1057 opportunities for hand hygiene observed among all categories of HCWs, overall compliance enhanced significantly from 32.1 to 39.4% (p < 0.001) respectively at pre- and post-intervention. Nurses were the most compliant with a significant improvement from 34.1 to 45.7% (p < 0.001) respectively at pre- and post-intervention. Furthermore, analysis by department showed significant improvement of compliance in orthopedic department (p < 0.001), maxillofacial-surgery department (p < 0.001), pediatrics department (p = 0.013), and emergencies (p = 0.038).

Conclusion
This study showed the feasibility and effectiveness of a health-setting-based intervention to enhance hand hygiene observance in the context of a developing country.