bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements needed to support people living and working with a rare disease in Northern Ireland: current rare disease support perceived as inadequate
Authors: McMullan Julie , Crowe Ashleen L. , Bailie Caitlin , Moore Kerry , McMullan Lauren S. , Shamandi Nahid , McAneney Helen , McKnight Amy Jayne 
Published: November 2020

AbstractBackgroundMany people living and working with rare diseases describe consistent difficulties accessing appropriate information and support. In this study an evaluation of the awareness of rare diseases, alongside related information and educational resources available for patients, their families and healthcare professionals, was conducted in 2018–2019 using an online survey and semi-structured interviews with rare disease collaborative groups (charities, voluntary and community groups) active across Northern Ireland (NI).MethodsThis study had 2 stages. Stage 1 was an online survey and stage 2 involved semi-structured interviews both with rare disease collaborative groups in Northern Ireland. The surveys and interviews were used to locate existing resources as well as identify gaps where the development of further resources would be appropriate.ResultsNinety-nine rare disease collaborative groups engaged with the survey with 31 providing detailed answers. Resources such as information, communication, ‘registries’, online services, training and improvements to support services were queried. Excellent communication is an important factor in delivering good rare disease support. Training for health professionals was also highlighted as an essential element of improving support for those with a rare disease to ensure they approach people with these unique and challenging diseases in an appropriate way. Carers were mentioned several times throughout the study; it is often felt they are overlooked in rare disease research and more support should be in place for them. Current care/support for those with a rare disease was highlighted as inadequate. Nine semi-structured interviews were conducted with rare disease collaborative groups. Reoccurring themes included a need for more effective information and communication, training for health professionals, online presence, support for carers, and involvement in research.ConclusionsAll rare disease collaborative groups agreed that current services for people living and working with a rare disease are not adequate. An important finding to consider in future research within the rare disease field is the inclusion of carers perceptions and experiences in studies. This research provides insight into the support available for rare diseases across Northern Ireland, highlights unmet needs, and suggests approaches to improve rare disease support.
Prevalence of mental health problems in Chinese schoolchildren: The influence of measuring impact score and combining information from multiple informants
Authors: Liu Li , Li Shuang , Pan Wen , Wang Lijuan , Zheng Yang , An Xiaoxia , Zhou Yan , Li Yanxia , Na Jun , Zhang Rui , Mu Huijuan , Dong Wen , Gao Yuan , Sun Wei , Pan Guowei , Yan Lingjun 
Published: November 2020

Abstract

Background
To measure the effects of using different combinations of multiple informants and the impact score on the estimated prevalence of mental health problems in Chinese schoolchildren.

Methods
Complete information on the Strengths and Difficulties Questionnaire (SDQ) were obtained from students (S), parents (P), and teachers (T) for 4986 schoolchildren (11–17 years-old). We used 3 criteria to determine the prevalence of mental health problems: SDQ cut-off value (previously established in the United Kingdom), SDQ cut-off value plus an impact score of 1 or more, or plus an impact score of 2 or more. A student was defined as having a mental health problem if any informant (S, P, or T) classified the child as ‘abnormal’. We compared the prevalence of mental health problems determined from 1 informant, 2 informants, and 3 informants.

Results
The prevalence of overall mental health problems increased with rising number of informants, but decreased with increasing impact score. When the impact score was not considered, the prevalence was 8.2% to 14.2% when rated by 1 informant, 18.8% to 24.7% when rated by 2 informants, and 28.3% when rated by all 3 informants. Failure to measure the impact score led to a two to threefold greater estimate of the prevalence of mental health problems.

Conclusions
The types, number, and combinations of multiple informants and use of the impact score must be considered when comparing the results of different studies. It is preferable to use multiple informants and have the impact score taken the impact into account to reflect the real burden of mental health burden in children and adolescent.
A biomedical Engineering Laboratory module for exploring involuntary muscle reflexes using Electromyography
Authors: Franz Karly S. , Patel Kramay , Kilkenny Dawn M. 
Published: November 2020

Abstract

Background
Undergraduate biomedical engineering (BME) students interested in pursuing a career in research and development of medical or physiological monitoring devices require a strong foundation in biosignal analysis as well as physiological theory. Applied learning approaches are reported to be effective for reinforcing physiological coursework; therefore, we propose a new laboratory protocol for BME undergraduate physiology courses that integrates both neural engineering and physiological concepts to explore involuntary skeletal muscle reflexes. The protocol consists of two sections: the first focuses on recruiting soleus motor units through transcutaneous electrical nerve stimulation (TENS), while the second focuses on exploring the natural stretch reflex with and without the Jendrassik maneuver. In this case study, third-year biomedical engineering students collected electromyographic (EMG) activity of skeletal muscle contractions in response to peripheral nerve stimulation using a BioRadio Wireless Physiology Monitor system and analyzed the corresponding signal parameters (latency and amplitude) using the MATLAB platform.

Results/protocol validation
Electrical tibial nerve stimulation successfully recruited M-waves in all 8 student participants and F-waves in three student participants. The students used this data to learn about orthodromic and antidromic motor fiber activation as well as estimate the neural response latency and amplitude. With the stretch reflex, students were able to collect distinct signals corresponding to the tendon strike and motor response. From this, they were able to estimate the sensorimotor conduction velocity. Additionally, a significant increase in the stretch reflex EMG amplitude response was observed when using the Jendrassik maneuver during the knee-jerk response. A student exit survey on the laboratory experience reported that the class found the module engaging and helpful for reinforcing physiological course concepts.

Conclusion
This newly developed protocol not only allows BME students to explore physiological responses using natural and electrically-induced involuntary reflexes, but demonstrates that budget-friendly commercially available devices are capable of eliciting and measuring involuntary reflexes in an engaging manner. Despite some limitations caused by the equipment and students’ lack of signal processing experience, this new laboratory protocol provides a robust framework for integrating engineering and physiology in an applied approach for BME students to learn about involuntary reflexes, neurophysiology, and neural engineering.
LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma
Authors: Teng Fei , Zhang Ju-Xiang , Chang Qi-Meng , Wu Xu-Bo , Tang Wei-Guo , Wang Jian-Fa , Feng Jin-Feng , Zhang Zi-Ping , Hu Zhi-Qiu 
Published: November 2020

Abstract
Background
Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined.

Methods
Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis.

Results
MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies.

Conclusions
MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.
Analysis of multicenter clinical trials with very low event rates
Authors: Kim Jiyu , Troxel Andrea B. , Halpern Scott D. , Volpp Kevin G. , Kahan Brennan C. , Morris Tim P. , Harhay Michael O. 
Published: November 2020

Abstract

Introduction
In a five-arm randomized clinical trial (RCT) with stratified randomization across 54 sites, we encountered low primary outcome event proportions, resulting in multiple sites with zero events either overall or in one or more study arms. In this paper, we systematically evaluated different statistical methods of accounting for center in settings with low outcome event proportions.

Methods
We conducted a simulation study and a reanalysis of a completed RCT to compare five popular methods of estimating an odds ratio for multicenter trials with stratified randomization by center: (i) no center adjustment, (ii) random intercept model, (iii) Mantel–Haenszel model, (iv) generalized estimating equation (GEE) with an exchangeable correlation structure, and (v) GEE with small sample correction (GEE-small sample correction). We varied the number of total participants (200, 500, 1000, 5000), number of centers (5, 50, 100), control group outcome percentage (2%, 5%, 10%), true odds ratio (1, > 1), intra-class correlation coefficient (ICC) (0.025, 0.075), and distribution of participants across the centers (balanced, skewed).

Results
Mantel–Haenszel methods generally performed poorly in terms of power and bias and led to the exclusion of participants from the analysis because some centers had no events. Failure to account for center in the analysis generally led to lower power and type I error rates than other methods, particularly with ICC = 0.075. GEE had an inflated type I error rate except in some settings with a large number of centers. GEE-small sample correction maintained the type I error rate at the nominal level but suffered from reduced power and convergence issues in some settings when the number of centers was small. Random intercept models generally performed well in most scenarios, except with a low event rate (i.e., 2% scenario) and small total sample size (n ≤ 500), when all methods had issues.

Discussion
Random intercept models generally performed best across most scenarios. GEE-small sample correction performed well when the number of centers was large. We do not recommend the use of Mantel–Haenszel, GEE, or models that do not account for center. When the expected event rate is low, we suggest that the statistical analysis plan specify an alternative method in the case of non-convergence of the primary method.
Negative pressure wound therapy (NPWT) on closed incisions to prevent surgical site infection in high-risk patients in hepatopancreatobiliary surgery: study protocol for a randomized controlled trial—the NP-SSI trial
Authors: Brennfleck Frank W. , Linsenmeier Lena , Junger Henrik H.G. , Schmidt Katharina M. , Werner Jens M. , Woehl Daniel , Zeman Florian , Mutzbauer Ingrid , Hutchinson James A. , Geissler Edward K. , Schlitt Hans J. , Brunner Stefan M. 
Published: November 2020

Abstract

Background
Incisional surgical site infections (iSSI) in hepatopancreatobiliary (HPB) surgery usually lead to prolonged hospital stays, consume valuable resources, and impact on patients’ outcome. Prophylactic closed incision negative pressure wound therapy (ciNPWT) to decrease wound complications has become available. Owing to an increasing number of studies, evidence for superiority in many indication areas has accumulated; however, in general surgery, there are a few data and those have shown contradictory results.

Methods
In this monocentric, prospective, randomized, controlled, two-armed study, the influence of ciNPWT on incisional surgical site infection rates after HPB operations will be investigated. A total of 222 patients will be randomized 1:1 to an interventional group (7-day treatment with ciNPWT) or a control group (treated with gauze dressing). The primary parameter to evaluate efficacy is the rate of incisional SSIs within 30 days after surgery. Additionally, several clinically relevant secondary outcomes will be assessed.

Discussion
A reduction in the rate of incisional SSIs would not only lead to a significant cost reduction and shorter postoperative length of stay, but may also improve postoperative quality of life for patients. While earlier publications have shown advantages for ciNPWT, recent studies did not confirm a positive effect regarding iSSI rate. Even if iSSI rate is not reduced, findings obtained from the secondary endpoints may be of clinical relevance, such as reduction of wound complication rates.

Trial registration
This trial has been registered in the German Clinical Trials Register, DRKS 00015136. Registered on 19 February 2019 and has been approved by the local ethics committee of the University of Regensburg: 18-1225-101.
Evolutionary engineering of E. coli MG1655 for tolerance against isoprenol
Authors: Babel Heiko , Krömer Jens O. 
Published: November 2020

AbstractBackgroundIsoprenol is the basis for industrial flavor and vitamin synthesis and also a promising biofuel. Biotechnological production of isoprenol withE. coliis currently limited by the high toxicity of the final product. Adaptive laboratory evolution (ALE) is a promising method to address complex biological problems such as toxicity.ResultsHere we applied this method successfully to evolveE. colitowards higher tolerance against isoprenol, increasing growth at the half-maximal inhibitory concentration by 47%. Whole-genome re-sequencing of strains isolated from three replicate evolutions at seven time-points identified four major target genes for isoprenol tolerance:fabF, marC, yghB,androb. We could show that knock-out ofmarCand expression of mutated Rob H(48) → frameshiftincreased tolerance against isoprenol and butanol. RNA-sequencing showed that the deletion identified upstream ofyghBcorrelated with a strong overexpression of the gene. The knock-out ofyghBdemonstrated that it was essential for isoprenol tolerance. The mutated Rob protein andyghBdeletion also lead to increased vanillin tolerance.ConclusionThrough ALE, novel targets for strain optimization in isoprenol production and also the production of other fuels, such as butanol, could be obtained. Their effectiveness could be shown through re-engineering. This paves the way for further optimization ofE. colifor biofuel production.
Prediction of Alzheimer’s disease biomarker status defined by the ‘ATN framework’ among cognitively healthy individuals: results from the EPAD longitudinal cohort study
Authors:   The European Prevention of Alzheimer’s Dementia (EPAD) Consortium, Calvin Catherine M. , de Boer Casper , Raymont Vanessa , Gallacher John , Koychev Ivan 
Published: November 2020

Abstract

Background
The Amyloid/Tau/Neurodegeneration (ATN) framework has been proposed as a means of evidencing the biological state of Alzheimer’s disease (AD). Predicting ATN status in pre-dementia individuals therefore provides an important opportunity for targeted recruitment into AD interventional studies. We investigated the extent to which ATN-defined biomarker status can be predicted by known AD risk factors as well as vascular-related composite risk scores.

Methods
One thousand ten cognitively healthy older adults were allocated to one of five ATN-defined biomarker categories. Multinomial logistic regression tested risk factors including age, sex, education, APOE4, family history of dementia, cognitive function, vascular risk indices (high systolic blood pressure, body mass index (BMI), high cholesterol, physical inactivity, ever smoked, blood pressure medication, diabetes, prior cardiovascular disease, atrial fibrillation and white matter lesion (WML) volume), and three vascular-related composite scores, to predict five ATN subgroups; ROC curve models estimated their added value in predicting pathology.

Results
Age, APOE4, family history, BMI, MMSE and white matter lesions (WML) volume differed between ATN biomarker groups. Prediction of Alzheimer’s disease pathology (versus normal AD biomarkers) improved by 7% after adding family history, BMI, MMSE and WML to a ROC curve that included age, sex and APOE4. Risk composite scores did not add value.

Conclusions
ATN-defined Alzheimer’s disease biomarker status prediction among cognitively healthy individuals is possible through a combination of constitutional and cardiovascular risk factors but established dementia composite risk scores do not appear to add value in this context.
An itchy erythematous papular skin rash as a possible early sign of COVID-19: a case report
Authors: Serafini Alice , Kurotschka Peter Konstantin , Bertolani Mariabeatrice , Riccomi Silvia 
Published: November 2020

Abstract

Background
Several recent studies suggest the possibility of a skin rash being a clinical presentation of coronavirus disease 2019 (COVID-19). The purpose of this case report is to bring attention to skin manifestations in the early stage of COVID-19 in order to support frontline physicians in their crucial activity of case identification.

Case presentation
The patient is an Italian 32-year-old female nurse who had several close contacts with multiple patients with COVID-19 as part of her professional workload. On March 13, 2020, the patient developed an itchy, erythematous papular rash (sparing only her face, scalp, and abdomen), which lasted for 10 days. The rash was accompanied by a feeling of general fatigue that gradually worsened over the following days and has continued for 5 months (until the end of July 2020). During the first week of remote assessment carried out by her general practitioner, the patient gradually developed a dry cough, intermittent fever, and diarrhoea and then had a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Her skin manifestations disappeared completely 48 days after the onset of the disease, followed by the disappearance of the dry cough.

Conclusions
In light of recent studies, this case report suggests that skin manifestations, when taken into account with other situational factors (such as profession and patient history) should be taken into proper consideration by frontline physicians as possibly being caused by SARS-CoV-2. Early identification of COVID-19 is a key part of the strategy of case detection and case isolation. To enhance this activity, further research is needed to establish frequency, symptoms, signs, and pathogenesis of skin manifestations in patients with COVID-19.
A fair credit-based incentive mechanism for routing in DTN-based sensor network with nodes’ selfishness
Authors: Mao Yuxin , Zhou Chenqian , Qi Ji , Zhu Xudong 
Published: November 2020

Abstract
Due to the unguaranteed connectivity, wireless sensor networks based on delay tolerant network (DTN) are typically characterized by the opportunistic forwarding mechanism in transmission. Such a mechanism requires nodes to participate in forwarding messages actively. However, when the mechanism is used in the real world, selfish nodes will exhibit some non-cooperation behaviors. Therefore, some incentive mechanism may be designed to encourage selfish nodes. In order to solve the selfishness problem, we propose a fair credit-based incentive mechanism for routing in DTN-based sensor networks. In this mechanism, when a source node sends messages to its destination, each relay node will be rewarded with some credits. The accumulated credits are then used to evaluate the level of cooperation in the network. The selfish nodes with few credits are not able to get enough service from other nodes. With the fair incentive, all participating relays will get equal rewards by the trusted third party. In order to evaluate the proposed mechanism, we also perform some simulation, and the results demonstrate that the method can be used to support efficient routing for DTN-based sensor networks.
Common fixed points of monotone ρ-nonexpansive semigroup in modular spaces
Authors: El Harmouchi Noureddine , Chaira Karim , Marhrani El Miloudi 
Published: November 2020

Abstract
In this paper, we consider the class of monotone ρ-nonexpansive semigroups and give existence and convergence results for common fixed points. First, we prove that the set of common fixed points is nonempty in uniformly convex modular spaces and modular spaces. Then we introduce an iteration algorithm to approximate a common fixed point for the same class of semigroups.