bluuebunny/crossref_metadata_2025_split huggingface dataset:
An innovative phase II trial to establish proof of efficacy and optimal dose of a new inhaled epithelial sodium channel inhibitor BI 1265162 in adults and adolescents with cystic fibrosis: BALANCE-CFTM1
Authors: Goss Christopher H. , Jain Raksha , Seibold Wolfgang , Picard Anne-Caroline , Hsu Ming-Chi , Gupta Abhya , Fajac Isabelle 
Published: October 2020

Inhibition of the epithelial sodium channel (ENaC) represents an important, mutation-agnostic therapeutic approach to restore airway surface liquid in patients with cystic fibrosis (CF). A phase II trial of the ENaC inhibitor BI 1265162, inhaledviathe Respimat® Soft Mist™ inhaler, in patients aged ≥12 years with CF is being conducted to assess the efficacy and safety of BI 1265162, on top of standard CF treatment (www.clinicaltrials.govidentifierNCT04059094).BALANCE-CF™ 1 is a multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-ranging trial consisting of 2 weeks’ screening, 4 weeks’ randomised treatment and 1 week follow-up. 98 patients, including ≥21 adolescents, will be randomised. First, 28 patients will be allocated to the highest dose of BI 1265162 (200 µg twice daily) or placebo in a 1:1 ratio. The remaining 70 patients will be allocated to one of five treatment arms (200 µg, 100 µg, 50 µg, 20 µg or placebo twice daily), with a final distribution ratio of 2:1:1:1:2. Recruitment and randomisation will begin with adult patients. An independent data monitoring committee will review safety data to advise on inclusion of adolescents and study continuation. A futility analysis will be conducted after 28 patients to prevent exposure of further patients in case of insufficient evidence of clinical efficacy. The design ensures that potential for effect is assessed ahead of wider enrolment, allowing investigation of a dose–response effect with minimal patient numbers.The results will increase understanding of efficacy, safety and optimal dosing of the inhaled ENaC inhibitor BI 1265162 in adults and adolescents with CF.
Aerosol delivery aspects within a high-flow therapy system in COPD patients
Authors: Madney Yasmin M. , Laz Nabila Ibrahim , Elberry Ahmed A. , Rabea Hoda , Abdelrahim Mohamed E.A. 
Published: October 2020

There is a lack of information about the influence of patient interfaces such as facemasks or mouthpieces on the effective dose of aerosolised drugs while using high-flow therapy in a clinical setting. These interfaces can improve pulmonary drug delivery over nasal cannulas but patient preference and comfort should also be considered.The present work was to determine the effect of three different interfaces (nasal cannula, valved face mask, and mouthpiece) when combined with titrated oxygen flow on aerosol delivery in patients with COPD hospitalised due to acute exacerbation.The variations between these interfaces were addressed in terms of change in lung function measurements pre-and post-inhalation, the delivered salbutamol dose, and patient tolerance to each interface.A high-flow nasal cannula was the most comfortable interface used. However, its pulmonary drug delivery was significantly lower than both the valved face mask and mouthpiece (p<0.05). Although drug delivery was different with the three tested interfaces, the lung function improvements were similar.
Development and comparison of RNA-sequencing pipelines for more accurate SNP identification: practical example of functional SNP detection associated with feed efficiency in Nellore beef cattle
Authors: Lam S. , Zeidan J. , Miglior F. , Suárez-Vega A. , Gómez-Redondo I. , Fonseca P. A. S. , Guan L. L. , Waters S. , Cánovas A. 
Published: October 2020

Abstract
Background
Optimization of an RNA-Sequencing (RNA-Seq) pipeline is critical to maximize power and accuracy to identify genetic variants, including SNPs, which may serve as genetic markers to select for feed efficiency, leading to economic benefits for beef production. This study used RNA-Seq data (GEO Accession ID: PRJEB7696 and PRJEB15314) from muscle and liver tissue, respectively, from 12 Nellore beef steers selected from 585 steers with residual feed intake measures (RFI; n = 6 low-RFI, n = 6 high-RFI). Three RNA-Seq pipelines were compared including multi-sample calling from i) non-merged samples; ii) merged samples by RFI group, iii) merged samples by RFI and tissue group. The RNA-Seq reads were aligned against the UMD3.1 bovine reference genome (release 94) assembly using STAR aligner. Variants were called using BCFtools and variant effect prediction (VeP) and functional annotation (ToppGene) analyses were performed.

Results
On average, total reads detected for Approach i) non-merged samples for liver and muscle, were 18,362,086.3 and 35,645,898.7, respectively. For Approach ii), merging samples by RFI group, total reads detected for each merged group was 162,030,705, and for Approach iii), merging samples by RFI group and tissues, was 324,061,410, revealing the highest read depth for Approach iii). Additionally, Approach iii) merging samples by RFI group and tissues, revealed the highest read depth per variant coverage (572.59 ± 3993.11) and encompassed the majority of localized positional genes detected by each approach. This suggests Approach iii) had optimized detection power, read depth, and accuracy of SNP calling, therefore increasing confidence of variant detection and reducing false positive detection. Approach iii) was then used to detect unique SNPs fixed within low- (12,145) and high-RFI (14,663) groups. Functional annotation of SNPs revealed positional candidate genes, for each RFI group (2886 for low-RFI, 3075 for high-RFI), which were significantly (P < 0.05) associated with immune and metabolic pathways.

Conclusion
The most optimized RNA-Seq pipeline allowed for more accurate identification of SNPs, associated positional candidate genes, and significantly associated metabolic pathways in muscle and liver tissues, providing insight on the underlying genetic architecture of feed efficiency in beef cattle.
Genome-wide patterns of differentiation within and among U.S. commercial honey bee stocks
Authors: Saelao Perot , Simone-Finstrom Michael , Avalos Arian , Bilodeau Lelania , Danka Robert , de Guzman Lilia , Rinkevich Frank , Tokarz Philip 
Published: October 2020

Abstract
Background
The population genetics of U.S. honey bee stocks remain poorly characterized despite the agricultural importance of Apis mellifera as the major crop pollinator. Commercial and research-based breeding programs have made significant improvements of favorable genetic traits (e.g. production and disease resistance). The variety of bees produced by artificial selection provides an opportunity to characterize the genetic diversity and regions of the genome undergoing selection in commonly managed stocks.

Results
Pooled sequencing of eight honey bee stocks found strong genetic similarity among six of the stocks. Two stocks, Pol-line and Hilo, showed significant differentiation likely due to their intense and largely closed breeding for resistance to the parasitic Varroa mite. Few variants were identified as being specific to any one stock, indicating potential admixture among the sequenced stocks. Juxtaposing the underlying genetic variation of stocks selected for disease- and parasite-resistance behavior, we identified genes and candidate regions putatively associated with resistance regulated by hygienic behavior.

Conclusion
This study provides important insights into the distinct genetic characteristics and population diversity of honey bee stocks used in the United States, and provides further evidence of high levels of admixture in commercially managed honey bee stocks. Furthermore, breeding efforts to enhance parasite resistance in honey bees may have created unique genetic profiles. Genomic regions of interest have been highlighted for potential future work related to developing genetic markers for selection of disease and parasite resistance traits. Due to the vast genomic similarities found among stocks in general, our findings suggest that additional data regarding gene expression, epigenetic and regulatory information are needed to more fully determine how stock phenotypic diversity is regulated.
Feasibility of remote digital monitoring using wireless Bluetooth monitors, the Smart Angel™ app and an original web platform for patients following outpatient surgery: a prospective observational pilot study
Authors: Chevallier Thierry , Buzancais Gautier , Occean Bob-Valéry , Rataboul Pierre , Boisson Christophe , Simon Natacha , Lannelongue Ariane , Chaniaud Noémie , Gricourt Yann , Lefrant Jean-Yves , Cuvillon Philippe 
Published: October 2020

Abstract
Background
Remote monitoring of mean arterial blood pressure (MAP), heart rate (HR) or oxygen saturation (SpO2) remains a challenge in outpatient surgery. This study evaluates a new digital technology (Smart Angel™) for remotely monitoring hemodynamic data in real time: data transmitted from the patient’s home to a central server, using a dedicated web-based software package.

Methods
Adults scheduled for elective outpatient surgery were prospectively enrolled. In the first 5 postoperative days, patients completed a self-report questionnaire (pain, comfort, nausea, vomiting) and recorded SpO2, HR and MAP via two wireless Bluetooth monitors connected to a 4G tablet to transmit the data to a website, in real time, using Smart Angel™ software. Before transmission to the website, these data were also self-reported by the patient on a paper form. The primary outcome was the proportion of variables (self-monitored physiological data + questionnaire scores) correctly transmitted to the hospital via the system compared with the paper version.
On Day 5, a system usability scale survey (SUS score 1–100) was also attributed.

Results
From May 2018 to September 2018, data were available for 29 out of 30 patients enrolled (1 patient was not discharged from hospital after surgery). The remote monitoring technology recorded 2038 data items (62%) compared with 2656 (82%) items recorded on the paper form (p = 0.001). The most common errors with the remote technology were software malfunctioning when starting the MAP monitor and malfunctioning between the tablet and the Bluetooth monitor. No serious adverse events were noted. The SUS score for the system was 85 (68–93) for 26 patients.

Conclusion
This work evaluates the ability of a pilot system for monitoring remote physiological data using digital technology after ambulatory surgery and highlights the digital limitations of this technology. Technological improvements are required to reduce malfunctioning (4G access, transmission between apps).

Trial registration
ClinicalTrials.gov (NCT03464721) (March 8, 2018).
Predictors of 30-day and 90-day mortality among hemorrhagic and ischemic stroke patients in urban Uganda: a prospective hospital-based cohort study
Authors: Namale Gertrude , Kamacooko Onesmus , Makhoba Anthony , Mugabi Timothy , Ndagire Maria , Ssanyu Proscovia , Ddamulira John Bosco M. , Yperzeele Laetitia , Cras Patrick , Ddumba Edward , Seeley Janet , Newton Robert 
Published: October 2020

Abstract
Background
We report here on a prospective hospital-based cohort study that investigates predictors of 30-day and 90-day mortality and functional disability among Ugandan stroke patients.

Methods
Between December 2016 and March 2019, we enrolled consecutive hemorrhagic stroke and ischemic stroke patients at St Francis Hospital Nsambya, Kampala, Uganda. The primary outcome measure was mortality at 30 and 90 days. The modified Ranking Scale wasused to assess the level of disability and mortality after stroke. Stroke severity at admission was assessed using the National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS). Examination included clinical neurological evaluation, laboratory tests and brain computed tomography (CT) scan. Kaplan-Meier curves and multivariate Cox proportional hazard model were used for unadjusted and adjusted analysis to predict mortality.

Results
We enrolled 141 patients; 48 (34%) were male, mean age was 63.2 (+ 15.4) years old; 90 (64%) had ischemic and 51 (36%) had hemorrhagic stroke; 81 (57%) were elderly (≥ 60 years) patients. Overall mortality was 44 (31%); 31 (23%) patients died within the first 30 days post-stroke and, an additional 13 (14%) died within 90 days post-stroke. Mortality for hemorrhagic stroke was 19 (37.3%) and 25 (27.8%) for ischemic stroke. After adjusting for age and sex, a GCS score below < 9 (adjusted hazard ratio [aHR] =3.49, 95% CI: 1.39–8.75) was a significant predictor of 30-day mortality. GCS score < 9 (aHR =4.34 (95% CI: 1.85–10.2), stroke severity (NIHSS ≥21) (aHR = 2.63, 95% CI: (1.68–10.5) and haemorrhagic stroke type (aHR = 2.30, 95% CI: 1.13–4.66) were significant predictors of 90-day mortality. Shorter hospital stay of 7–13 days (aHR = 0.31, 95% CI: 0.11–0.93) and being married (aHR = 0.22 (95% CI: 0.06–0.84) had protective effects for 30 and 90-day mortality respectively.

Conclusion
Mortality is high in the acute and sub-acute phase of stroke. Low levels of consciousness at admission, stroke severity, and hemorrhagic stroke were associated with increased higher mortality in this cohort of Ugandan stroke patients. Being married provided a protective effect for 90-day mortality. Given the high mortality during the acute phase, critically ill stroke patients would benefit from early interventions established as the post-stroke- standard of care in the country.
A physical activity program versus usual care in the management of quality of life for pre-frail older adults with chronic pain: randomized controlled trial
Authors: Otones Pedro , García Eva , Sanz Teresa , Pedraz Azucena 
Published: October 2020

Abstract
Background
Exercise has shown being effective for managing chronic pain and preventing frailty status in older adults but the effect of an exercise program in the quality of life of pre-frail older adults with chronic pain remains unclear. Our objective was to evaluate the effectiveness of multicomponent structured physical exercise program for pre-frail adults aged 65 years or more with chronic pain to improve their perceived health related quality of life, compared with usual care.

Methods
Open label randomized controlled trial. Participants were community-dwelling pre-frail older adults aged 65 years or older with chronic pain and non-dependent for basic activities of daily living attending a Primary Healthcare Centre. Forty-four participants were randomly allocated to a control group (n = 20) that received usual care or an intervention group (n = 24) that received an 8-week physical activity and education program. Frailty status (SHARE Frailty Index), quality of life (EuroQol-5D-5L), pain intensity (Visual Analogue Scale), physical performance (Short Physical Performance Battery) and depression (Yessavage) were assessed at baseline, after the intervention and after 3 months follow-up. The effect of the intervention was analysed by mean differences between the intervention and control groups.

Results
The follow-up period (3 months) was completed by 32 patients (73%), 17 in the control group and 15 in the intervention group. Most participants were women (78.1%) with a mean age (standard deviation) of 77.2 (5.9) years and a mean pain intensity of 48.1 (24.4) mm. No relevant differences were found between groups at baseline. After the intervention, mean differences in the EuroQol Index Value between control and intervention groups were significant (− 0.19 95% CI(− 0.33- -0.04)) and remained after 3 months follow-up (− 0.21 95% CI(− 0.37- -0.05)). Participants in the exercise group showed better results in pain intensity and frailty after the intervention, and an improvement in physical performance after the intervention and after 3 months.

Conclusions
An eight-week physical activity and education program for pre-frail older adults with chronic pain, compared with usual care, could be effective to improve quality of life after the intervention and after three-months follow-up.

Study registration details
This study was retrospectively registered in ClinicalTrials.gov with the identifier NCT04045535.
The impact of dementia and language on hospitalizations: a retrospective cohort of long-term care residents
Authors: Riad Karine , Webber Colleen , Batista Ricardo , Reaume Michael , Rhodes Emily , Knight Braden , Prud’homme Denis , Tanuseputro Peter 
Published: October 2020

Abstract
Background
Hospitalizations carry considerable risks for frail, elderly patients; this is especially true for patients with dementia, who are more likely to experience delirium, falls, functional decline, iatrogenic complications, and infections when compared to their peers without dementia. Since up to two thirds of patients in long-term care (LTC) facilities have dementia, there is interest in identifying factors associated with transitions from LTC facilities to hospitals. The purpose of this study was to investigate the association between dementia status and incidence of hospitalization among residents in LTC facilities in Ontario, Canada, and to determine whether this association is modified by linguistic factors.

Methods
We used linked administrative databases to establish a prevalent cohort of 81,188 residents in 628 LTC facilities from April 1st 2014 to March 31, 2017. Diagnoses of dementia were identified with a previously validated algorithm; all other patient characteristics were obtained from in-person assessments. Residents’ primary language was coded as English or French; facility language (English or French) was determined using language designation status according to the French Language Services Act. We identified all hospitalizations within 3 months of the first assessment performed after April 1st 2014. We performed multivariate logistic regression analyses to determine the impact of dementia and resident language on the incidence of hospitalization; we also considered interactions between dementia and both resident language and resident-facility language discordance.

Results
The odds of hospitalization were 39% lower for residents with dementia compared to residents without dementia (OR 0.61, 95% CI 0.57–0.65). Francophones had lower odds of hospitalization than Anglophones, but this difference was not statistically significant (OR 0.91, 95% CI 0.81–1.03). However, Francophones without dementia were significantly less likely to be hospitalized compared to Anglophones without dementia (OR 0.71, 95% CI 0.53–0.94). Resident-facility language discordance did not significantly affect hospitalizations.

Conclusions
Residents in LTC facilities were generally less likely to be hospitalized if they had dementia, or if their primary language was French and they did not have dementia. These findings could be explained by differences in end-of-life care goals; however, they could also be the result of poor patient-provider communication.
Clinical characteristics and manifestations in older patients with COVID-19
Authors: Wei Chenchen , Liu Ya , Liu Yapeng , Zhang Kai , Su Dezhen , Zhong Ming , Meng Xiao 
Published: October 2020

AbstractBackgroundTo investigate the clinical characteristics and manifestations of older patients with coronavirus disease 2019 (COVID-19).MethodsIn this retrospective study, 566 patients with confirmed COVID-19 were enrolled and the clinical characteristics, laboratory findings, complications and outcome data were collected and analyzed.ResultsAmong the 566 patients (median age, 61.5 years) with COVID-19, 267 (47.2%) patients were male and 307 (54.2%) were elderly. Compared with younger patients, older patients had more underlying comorbidities and laboratory abnormalities. A higher rate of acute respiratory distress syndrome (ARDS), acute cardiac injury and heart failure was observed in the older group as compared with younger and middle-aged groups, particularly those oldest-old patients had more multi-organ damage. Older patients with COVID-19 were more likely to suffer from acute cardiac injury in cases with preexistenting cardiovascular diseases, while there was no difference among the three groups when patients had no history of cardiovascular diseases. Older patients presented more severe with the mortality of 18.6%, which was higher than that in younger and middle-aged patients (P < 0.05). Multivariable analysis showed that age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were associated with death in older patients, while glucocorticoids might be harmful.ConclusionsOlder patients, especially the oldest-old patients were more likely to exhibit significant systemic inflammation, pulmonary and extrapulmonary organ damage and a higher mortality. Advanced age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were independent predictors of death in older patients with COVID-19 and glucocorticoids should be carefully administered in older patients.
Utility of deep learning networks for the generation of artificial cardiac magnetic resonance images in congenital heart disease
Authors: Diller Gerhard-Paul , Vahle Julius , Radke Robert , Vidal Maria Luisa Benesch , Fischer Alicia Jeanette , Bauer Ulrike M. M. , Sarikouch Samir , Berger Felix , Beerbaum Philipp , Baumgartner Helmut , Orwat Stefan ,   for the German Competence Network for Congenital Heart Defects Investigators
Published: October 2020

Abstract
Background
Deep learning algorithms are increasingly used for automatic medical imaging analysis and cardiac chamber segmentation. Especially in congenital heart disease, obtaining a sufficient number of training images and data anonymity issues remain of concern.

Methods
Progressive generative adversarial networks (PG-GAN) were trained on cardiac magnetic resonance imaging (MRI) frames from a nationwide prospective study to generate synthetic MRI frames. These synthetic frames were subsequently used to train segmentation networks (U-Net) and the quality of the synthetic training images, as well as the performance of the segmentation network was compared to U-Net-based solutions trained entirely on patient data.

Results
Cardiac MRI data from 303 patients with Tetralogy of Fallot were used for PG-GAN training. Using this model, we generated 100,000 synthetic images with a resolution of 256 × 256 pixels in 4-chamber and 2-chamber views. All synthetic samples were classified as anatomically plausible by human observers. The segmentation performance of the U-Net trained on data from 42 separate patients was statistically significantly better compared to the PG-GAN based training in an external dataset of 50 patients, however, the actual difference in segmentation quality was negligible (< 1% in absolute terms for all models).

Conclusion
We demonstrate the utility of PG-GANs for generating large amounts of realistically looking cardiac MRI images even in rare cardiac conditions. The generated images are not subject to data anonymity and privacy concerns and can be shared freely between institutions. Training supervised deep learning segmentation networks on this synthetic data yielded similar results compared to direct training on original patient data.