bluuebunny/crossref_metadata_2025_split huggingface dataset:
An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel
Authors: Urrutia Janire , Aguado Alejandra , Gomis-Perez Carolina , Muguruza-Montero Arantza , Ballesteros Oscar R. , Zhang Jiaren , Nuñez Eider , Malo Covadonga , Chung Hee Jung , Leonardo Aritz , Bergara Aitor , Villarroel Alvaro 
Published: May 2021

AbstractBackgroundThe amino acid sequence of proteins generally carries all the necessary information for acquisition of native conformations, but the vectorial nature of translation can additionally determine the folding outcome. Such consideration is particularly relevant in human diseases associated to inherited mutations leading to structural instability, aggregation, and degradation. Mutations in the KCNQ2 gene associated with human epilepsy have been suggested to cause misfolding of the encoded Kv7.2 channel. Although the effect on folding of mutations in some domains has been studied, little is known of the way pathogenic variants located in the calcium responsive domain (CRD) affect folding. Here, we explore how a Kv7.2 mutation (W344R) located in helix A of the CRD and associated with hereditary epilepsy interferes with channel function.ResultsWe report that the epilepsy W344R mutation within the IQ motif of CRD decreases channel function, but contrary to other mutations at this site, it does not impair the interaction with Calmodulin (CaM) in vitro, as monitored by multiple in vitro binding assays. We find negligible impact of the mutation on the structure of the complex by molecular dynamic computations. In silico studies revealed two orientations of the side chain, which are differentially populated by WT and W344R variants. Binding to CaM is impaired when the mutated protein is produced in cellulo but not in vitro, suggesting that this mutation impedes proper folding during translation within the cell by forcing the nascent chain to follow a folding route that leads to a non-native configuration, and thereby generating non-functional ion channels that fail to traffic to proper neuronal compartments.ConclusionsOur data suggest that the key pathogenic mechanism of Kv7.2 W344R mutation involves the failure to adopt a configuration that can be recognized by CaM in vivo but not in vitro.
Effect of different corticosteroid regimes for hospitalised patients with exacerbated COPD: pooled analysis of individual participant data from the REDUCE and CORTICO-COP trials
Authors: Sivapalan Pradeesh , Rutishauser Jonas , Ulrik Charlotte Suppli , Leuppi Jörg D. , Pedersen Lars , Mueller Beat , Eklöf Josefin , Biering-Sørensen Tor , Gottlieb Vibeke , Armbruster Karin , Janner Julie , Moberg Mia , Lapperre Therese S. , Nielsen Thyge L. , Browatzki Andrea , Mathioudakis Alexander , Vestbo Jørgen , Schüetz Philipp , Jensen Jens-Ulrik 
Published: May 2021

Abstract
Background
Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2–5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens.

Methods
We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2–5-day regimens were compared, with adjustment for baseline differences.

Results
The number of days alive and out of hospital within 14 days from recruitment was higher for the 2–5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0–8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4–4.9; p < 0.001). The 14-day AECOPD group had longer hospital stays (mean difference, 5.4 days [standard error ± 0.6]; p < 0.0001) and decreased likelihood of discharge within 30 days (hazard ratio [HR] 0.5; 95% CI 0.4–0.6; p < 0.0001). Comparing the 14-day regimen and the 2–5 day regimen group showed no differences in the composite endpoint ‘death or ICU admission’ (odds ratio [OR] 1.4; 95% CI 0.8–2.3; p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9–2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4–1.5; p = 0.45) during the 6-month follow-up period.

Conclusion
14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2–5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.
Use of capnography for prediction of obstruction severity in non-intubated COPD and asthma patients
Authors: Pertzov Barak , Ronen Michal , Rosengarten Dror , Shitenberg Dorit , Heching Moshe , Shostak Yael , Kramer Mordechai R. 
Published: May 2021

Abstract
Background
Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD.

Methods
Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry.

Measurements and main results
Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13.

Conclusion
In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy.

Trial registration
clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114
Circ_0000745 strengthens the expression of CCND1 by functioning as miR-488 sponge and interacting with HuR binding protein to facilitate the development of oral squamous cell carcinoma
Authors: Li Kuangzheng , Fan Xiaosheng , Yan Ziyi , Zhan Jia , Cao Fangyun , Jiang Yixia 
Published: May 2021

Abstract
Background
The implication of circular RNAs (circRNAs) in human cancers has aroused much concern. In this study, we investigated the function of circ_0000745 and its potential functional mechanisms in oral squamous cell carcinoma (OSCC) to further understand OSCC pathogenesis.

Methods
The expression of circ_0000745, miR-488 and cyclin D1 (CCND1) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation capacity was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell cycle progression and cell apoptosis were determined by flow cytometry assay. The protein levels of CCND1, PCNA, Cleaved-caspase 3 and HuR were detected by western blot. Animal study was conducted to identify the role of circ_0000745 in vivo. The targeted relationship was verified by dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay.

Results
The expression of circ_0000745 was increased in OSCC tissues and cells. Circ_0000745 downregulation inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, as well as blocked tumor growth in vivo. MiR-488 was a target of circ_0000745, and circ_0000745 downregulation suppressed OSCC development by enriching miR-488. Besides, circ_0000745 regulated CCND1 expression by targeting miR-488. In addition, circ_0000745 regulated CCND1 expression by interacting with HuR protein. CCND1 knockdown also inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, and CCND1 overexpression recovered the inhibitory effects on OSCC cell malignant behaviors caused by circ_0000745 downregulation.

Conclusions
Circ_0000745 regulated the expression of CCND1 partly by acting as miR-488 sponge and interacting with HuR protein, thus promoting the progression of OSCC.
Assessment of medical equipment maintenance management: proposed checklist using Iranian experience
Authors: Arab-Zozani Morteza , Imani Ali , Doshmangir Leila , Dalal Koustuv , Bahreini Rona 
Published: May 2021

Abstract
Background
Effective maintenance management of medical equipment is one of the major issues for quality of care, for providing cost-effective health services and for saving scarce resources. This study aimed to develop a comprehensive checklist for assessing the medical equipment maintenance management (MEMM) in the Iranian hospitals.

Methods
This is a multi-methods study. First, data related to factors which affect the assessment of MEMM were collected through a systematic review in PubMed, ProQuest, Scopus, Embase, and web of science without any time limitation until October 2015, updated in June 2017. Then, we investigated these factors affecting using document review and interviews with experts in the Iranian hospitals. In the end, the results of the first and second stages were combined using content analysis and the final checklist was developed in a two-round Delphi.

Results
Using a combination of factors extracted from the systematic and qualitative studies, the primary checklist was developed in the form of assessment checklists in seven dimensions. The final checklist includes 7 dimensions and 19 sub-categories: “resources = 3,” “quality control = 3,” “information bank = 4,” “education = 1,” “service = 3,” “inspection and preventive maintenance = 2” and “design and implementation = 3.”

Conclusions
Developing an assessment checklist for MEMM provide a comprehensive framework for the proper implementation of accurate assessment of medical equipment maintenance. This checklist can be used to improve the profitability of health facilities and the reliability of medical equipment. In addition, it is implicated in the decision-making in support of selection, purchase, repair and maintenance of medical equipment, especially for capital equipment managers and medical engineers in hospitals and also for the assessment of this process.
Socioeconomic inequalities in curative healthcare-seeking for children under five before and after the free healthcare initiative in Sierra Leone: analysis of population-based survey data
Authors: Bognini Joel D. , Samadoulougou Sekou , Ouedraogo Mady , Kangoye Tiga David , Van Malderen Carine , Tinto Halidou , Kirakoya-Samadoulougou Fati 
Published: May 2021

Abstract
Background
Socioeconomic inequalities between and within countries lead to disparities in the use of health services. These disparities could lead to child mortality in children under 5 years by depriving them of healthcare. Therefore, initiatives to remove healthcare fees such as the Free Healthcare Initiative (FHCI) adopted in Sierra Leone can contribute to reducing these inequities in healthcare-seeking for children. This study aimed to assess the socioeconomic inequalities in healthcare-seeking for children under 5 years of age before and after the implementation of the FHCI.

Methods
Data were included on 1207, 2815, 1633, and 1476 children under 5 years of age with fever from the 2008, 2013, 2016, and 2019 nationwide surveys, respectively. Concentration curves were drawn for the period before (2008) and after (2013–2019) the implementation of the FHCI to assess socioeconomic inequalities in healthcare-seeking. Finally, Erreyger’s corrected concentration indices were calculated to understand the magnitude of these inequalities.

Results
Before the implementation of the FHCI, there were inequalities in healthcare-seeking for children under five (Erreyger’s corrected concentration index (CI) = 0.168, standard error (SE) = 0.049; p < 0.001) in favor of the wealthy households. These inequalities decreased after the implementation of the FHCI (CI = 0.061, SE = 0.033; p = 0.06 in 2013, CI = 0.039, SE = 0.04; p = 0.32 in 2016, and CI = − 0.0005, SE = 0.362; p = 0.98 in 2019). Furthermore, before the implementation of the FHCI, a significant pro-rich inequality in the districts of Kenema (CI = 0.117, SE = 0.168, p = 0.021), Kono (CI = 0.175, SE = 0.078, p = 0.028) and Western Area Urban (CI = 0.070, SE = 0.032, p = 0.031) has been observed. After the implementation of the FHCI in 2019, these disparities were reduced, 11 of the 14 districts had a CI around the value of equality, and only in 2 districts the pro-rich inequality were significant (Western Area Urban (CI = 0.035, SE = 0.016, p = 0.039) and Western Area Rural (CI = 0.066, SE = 0.030, p = 0.027)).

Conclusion
The results of this study demonstrated that socio-economic inequalities in healthcare-seeking for children have been considerably reduced after the FHCI in Sierra Leone. To further reduce these inequalities, policy actions can focus on the increase of availability of health services in the districts where the healthcare-seeking remained pro-rich.
Integrating equity and social justice for indigenous peoples in undergraduate health professions education in Canada: a framework from a critical review of literature
Authors: Blanchet Garneau Amélie , Bélisle Marilou , Lavoie Patrick , Laurent Sédillot Catherine 
Published: May 2021

AbstractUnderstanding how to create structural change by actively counteracting racialized ways of interacting with Indigenous peoples at an individual and organizational level within health care systems and health professions education is essential for creating a more inclusive, equitable, and healthier society. In health professions education, the primary means of teaching about health inequities has been to frame them as stemming from culturally or ethnically based issues. While attention to culturally specific practices can be valuable to health and healing in some contexts, education that solely focuses on Indigenous cultures risks perpetuating cultural stereotypes and othering, rather than focusing on how Eurocentric systems continue to exert oppressive effects on Indigenous peoples. We present an organizational transformation framework grounded in equitable partnerships from a comprehensive critical review of the literature on the integration of equity and social justice in undergraduate health professions education with a focus on Indigenous health. We did a thematic analysis of the results and discussions presented in the 26 selected articles to identify promising practices and challenges associated with the integration of equity and social justice in undergraduate health professions education. The framework resulting from this analysis is composed of three interrelated components: 1) adopt critical pedagogical approaches that promote Indigenous epistemologies; 2) partner with Indigenous students, educators and communities; 3) engage educators in critical pedagogical approaches and health equity issues. This framework could guide the development of contextually tailored interventions that contribute to decolonizing health professions education.
How birth outcomes among a cohort of Guatemalan women with a history of prior cesarean vary by mode or birth across different interpregnancy intervals
Authors: Harrison Margo S. , Garces Ana , Figueroa Lester , Westcott Jamie , Hambidge Michael , Krebs Nancy F. 
Published: May 2021

Abstract
Objectives
Our objectives were to analyze how pregnancy outcomes varied by cesarean birth as compared to vaginal birth across varying interpregnancy intervals (IPI) and determine if IPI modified mode of birth.

Methods
This secondary analysis used data from a prospective registry of home and hospital births in Chimaltenango, Guatemala from January 2017 through April 2020, through the Global Network for Women’s and Children’s Health Research. Bivariate comparisons and multivariable logistic regression were used to answer our study question, and the data was analyzed with STATA software v.15.1.

Results
Of 26,465 Guatemalan women enrolled in the registry, 2794 (10.6%) had a history of prior cesarean. 560 (20.1%) women delivered by vaginal birth after cesarean with the remaining 2,233 (79.9%) delivered by repeat cesarean. Repeat cesarean reduced the risk of needing a dilation and curettage compared to vaginal birth after cesarean, but this association did not vary by IPI, all p-values > p = 0.05. Repeat cesarean delivery, as compared to vaginal birth after cesarean, significantly reduced the likelihood a woman breastfeeding within one hour of birth (AOR ranged from 0.009 to 0.10), but IPI was not associated with the outcome. Regarding stillbirth, repeat cesarean birth reduced the likelihood of stillbirth as compared to vaginal birth (AOR 0.2), but again IPI was not associated with the outcome.

Conclusion
Outcomes by mode of delivery among a Guatemalan cohort of women with a history of prior cesarean birth do not vary by IPI.
Magnitude and associated factors of menstrual irregularity among undergraduate students of Debre Berhan University, Ethiopia
Authors: Zeru Abayneh Birlie , Gebeyaw Enguday Demeke , Ayele Esubalew Tesfahun 
Published: May 2021

Abstract
Background
Menstrual irregularity is a common problem among women aged from 21 to 25 years. Previously published work on menstrual irregularity used inconsistent definition which results in a difference in prevalence. Therefore the study aimed to assess the magnitude and associated factors of menstrual irregularity among undergraduate students of Debre Berhan University, Ethiopia.

Methods
A cross-sectional study design was carried out among 660 undergraduate female students at Debre Berhan University. To get representative study participants, a stratified sampling technique was used. To collect the data self-administered questionnaire was used. Physical examination and anthropometric measurement were also done. Data were analyzed by using SPSS version 21. Logistic regression analysis was done. A significant association was declared at a p-value less than 0.05.

Result
A total of 620 students participated in the present study with a response rate of 93.9%. Out of the total study participants, 32.6% (95% CI 29–36.5) participants had irregular menstrual cycle. Significant association was found between anemia (AOR = 2.1; 95%CI 1.337–3.441), alcohol intake (AOR = 2.4; 95%CI 1.25–4.666), < 5 sleep hours (AOR = 5.4; 95%CI 2.975–9.888), 6–7 sleep hours (AOR = 1.9; 95%CI 1.291–2.907), Perceived stress (AOR = 3.3; 95%CI 1.8322–5.940), iodine deficiency disorder (IDD) (AOR = 3.9; 95%CI 1.325–11.636) and underweight (AOR = 1.8; 95%CI 1.109–2.847) with menstrual irregularity.

Conclusion
The finding of this study reported a low magnitude of menstrual irregularity as compared to previous studies. Students should adopt healthier lifestyle practices (weight control, stress control, anemia control, and avoid alcohol intake) to control menstrual irregularity.
Feasibility and effectiveness of a novel dynamic arm support in persons with spinal muscular atrophy and duchenne muscular dystrophy
Authors: Janssen Mariska M. H. P. , Horstik Jolinda , Klap Paulien , de Groot Imelda J. M. 
Published: May 2021

Abstract
Background
Neuromuscular disorders (NMD) commonly affect the upper extremity. Due to muscle weakness, performance of daily activities becomes increasingly difficult, which leads to reduced independence and quality of life. In order to support the performance of upper extremity tasks, dynamic arm supports may be used. The Yumen Arm is a novel dynamic arm support specially developed for people with NMD. The aim of this study is to evaluate the feasibility and effectiveness of the Yumen Arm in persons with Duchenne Muscular Dystrophy (DMD) and persons with Spinal Muscular Atrophy (SMA).

Methods
Three persons with DMD and three persons with SMA participated in this study. All participants conducted a set of measures with and without the Yumen Arm. Outcome measures were: active range of motion of the arm and trunk (i.e. Reachable Workspace, Functional Workspace, and trunk movement), fatigue (OMNI-RPE), Performance of Upper Limb (PUL) scale and some additional activities of daily living. User experiences were collected using a questionnaire.

Results
The Yumen Arm could be used by all participants. Results showed a median increase in active range of motion (4% relative surface area), and a median increase of function ability (> 11% PUL score) when using the Yumen Arm. In addition, three out of four (data from 2 participants was missing) participants indicated that activity performance was less fatiguing when using the Yumen Arm. Four out of five (data from 1 participant was missing) participants indicated that they would like to use the Yumen Arm in their daily lives.

Conclusion
This study is one of the first studies describing a range of objective measures to examine the effectiveness of a dynamic arm support. Based on these measurements we can conclude that the Yumen Arm effectively improves arm function in NMD patients, however the effectiveness varies a lot between individual subjects. We provided detailed recommendations for the improvement of the Yumen Arm, and possible also for the development of other dynamic arm supports. This study showed a lot of variability between individual subjects, which emphasizes the importance of tuning dynamic arm supports based on individual user characteristics, such as scoliosis, functional capacity and muscle strength.