bluuebunny/crossref_metadata_2025_split huggingface dataset:
PyGNA: a unified framework for geneset network analysis
Authors: Fanfani Viola , Cassano Fabio , Stracquadanio Giovanni 
Published: October 2020

Abstract
Background
Gene and protein interaction experiments provide unique opportunities to study the molecular wiring of a cell. Integrating high-throughput functional genomics data with this information can help identifying networks associated with complex diseases and phenotypes.

Results
Here we introduce an integrated statistical framework to test network properties of single and multiple genesets under different interaction models. We implemented this framework as an open-source software, called Python Geneset Network Analysis (PyGNA). Our software is designed for easy integration into existing analysis pipelines and to generate high quality figures and reports. We also developed PyGNA to take advantage of multi-core systems to generate calibrated null distributions on large datasets. We then present the results of extensive benchmarking of the tests implemented in PyGNA and a use case inspired by RNA sequencing data analysis, showing how PyGNA can be easily integrated to study biological networks. PyGNA is available at http://github.com/stracquadaniolab/pygna and can be easily installed using the PyPi or Anaconda package managers, and Docker.

Conclusions
We present a tool for network-aware geneset analysis. PyGNA can either be readily used and easily integrated into existing high-performance data analysis pipelines or as a Python package to implement new tests and analyses. With the increasing availability of population-scale omic data, PyGNA provides a viable approach for large scale geneset network analysis.
Genotypes diversity of env gene of Bovine leukemia virus in Western Siberia
Authors: Blazhko Natalia , Vyshegurov Sultan , Donchenko Alexander , Shatokhin Kirill , Ryabinina Valeria , Plotnikov Kirill , Khodakova Alevtina , Pashkovskiy Sergey 
Published: October 2020

Abstract
Background
This study describes the biodiversity and properties of Bovine leukemia virus in Western Siberia. This paper explores the effect of different genotypes of the env gene of the cattle leukemia virus on hematological parameters of infected animals. The researchers focused on exploring the polymorphism of the env gene and, in doing so, discovered the new genotypes Ia and Ib, which differ from genotype I. Several hypotheses on the origin of the different genotypes in Siberia are discussed.

Results
We obtained varying length of the restriction fragments for genotypes I. Additionally using restrictase Hae III were received fragments was named genotype Ia, and genotype Ib. There are 2.57 ± 0.55% (20 out of 779) samples of genotype Ib which does not differ significantly from 1% (χ2 = 2.46). Other genotypes were observed in the cattle of Siberia as wild type genotypes (their frequency varied from 17.84 to 32.73%). The maximum viral load was observed in animals with the II and IV viral genotypes (1000–1400 viral particles per 1000 healthy cells), and the minimum viral load was observed animals with genotype Ib (from 700 to 900 viral particles per 1000 healthy cells).

Conclusions
The probability of the direct introduction of genotype II from South America to Siberia is extremely small and it is more likely that the strain originated independently in an autonomous population with its distribution also occurring independently. A new variety of genotype I (Ib) was found, which can be both a neoplasm and a relict strain.
Hormonal and metabolites responses in Fusarium wilt-susceptible and -resistant watermelon plants during plant-pathogen interactions
Authors: Kasote Deepak M. , Jayaprakasha G. K. , Ong Kevin , Crosby Kevin M. , Patil Bhimanagouda S. 
Published: October 2020

Abstract
Background
Fusarium oxysporum f. sp. niveum (FON) causes Fusarium wilt in watermelon. Several disease-resistant watermelon varieties have been developed to combat Fusarium wilt. However, the key metabolites that mount defense responses in these watermelon varieties are unknown. Herein, we analyzed hormones, melatonin, phenolic acids, and amino acid profiles in the leaf tissue of FON zero (0)-resistant (PI-296341, Calhoun Grey, and Charleston Grey) and -susceptible (Sugar Baby) watermelon varieties before and after infection.

Results
We found that jasmonic acid-isoleucine (JA-Ile) and methyl jasmonate (MeJA) were selectively accumulated in one or more studied resistant varieties upon infection. However, indole-3-acetic acid (IAA) was only observed in the FON 0 inoculated plants of all varieties on the 16th day of post-inoculation. The melatonin content of PI-296341 decreased upon infection. Conversely, melatonin was only detected in the FON 0 inoculated plants of Sugar Baby and Charleston Grey varieties. On the 16th day of post-inoculation, the lysine content in resistant varieties was significantly reduced, whereas it was found to be elevated in the susceptible variety.

Conclusions
Taken together, Me-JA, JA-Ile, melatonin, and lysine may have crucial roles in developing defense responses against the FON 0 pathogen, and IAA can be a biomarker of FON 0 infection in watermelon plants.
A cross-sectional survey assessing the preparedness of the long-term care sector to respond to the COVID-19 pandemic in Ontario, Canada
Authors: Siu Henry Yu-Hin , Kristof Lorand , Elston Dawn , Hafid Abe , Mather Fred 
Published: October 2020

Abstract
Background
The COVID-19 pandemic is a significant public health emergency that impacts all sectors of healthcare. The negative health outcomes for the COVID-19 infection have been most severe in the frail elderly dwelling in Canadian long-term care (LTC) homes.

Methods
An online cross-sectional survey of Ontario LTC Clinicians working in LTC homes in Ontario Canada was conducted to provide the clinician perspective on the preparedness and engagement of the LTC sector during the COVID-19 pandemic. The survey questionnaire was developed in collaboration with the Ontario Long-Term Care Clinicians organization (OLTCC) and was distributed between March 30, 2020 to May 25, 2020. All registered members of the OLTCC and Nurse-led LTC Outreach Teams were invited to participate. The primary outcomes were: 1) the descriptive report of the screening measures implemented, communication and information received, and the preparation of the respondent’s LTC home to a potential COVID-19 outbreak; and 2) the level of agreement, as reported using a five-point Likert scale), to COVID-19 preparedness statements for the respondent’s LTC home was also assessed.

Results
The overall response rate was 54% (160/294). LTC homes implemented a wide range of important interventions (e.g. instituting established respiratory isolation protocols, active screening of new LTC admissions, increasing education on infection control processes, encouraging sick staff to take time off, etc). Ample communications pertinent to the pandemic were received from provincial LTC organizations, the government and public health officials. However, the feasibility of implementing public health recommendations, as well as the engagement of the LTC sector in pandemic planning were identified as areas of concern. Medical director status was associated with an increased knowledge of local implementation of interventions to mitigate COVID-19, as well as endorsing increased access to reliable COVID-19 information and resources to manage a potential COVID-19 outbreak in their LTC home.

Conclusions
This study highlights the communication and implementation of recommendations in the Ontario LTC sector, despite some concerns regarding feasibility. Importantly, LTC clinician respondents clearly indicated that better engagement with LTC leaders is needed to plan a coordinated pandemic response.
Prenatal diagnosis of Norrie disease after whole exome sequencing of an affected proband during an ongoing pregnancy: a case report
Authors: Marakhonov Andrey V. , Mishina Irina A. , Kadyshev Vitaly V. , Repina Svetlana A. , Shurygina Maria F. , Shchagina Olga A. , Vasserman Natalya N. , Vasilyeva Tatyana A. , Kutsev Sergey I. , Zinchenko Rena A. 
Published: October 2020

Abstract
Background
Hereditary ophthalmic pathology is a genetically heterogeneous group of diseases that occur either as an isolated eye disorder or as a symptom of hereditary syndromes (chromosomal or monogenic). Thus, a diagnostic search in some cases of ophthalmic pathology can be time- and cost-consuming. The most challenging situation can arise when prenatal diagnosis is needed during an ongoing pregnancy.

Case presentation
A family was referred to the Research Centre for Medical Genetics (RCMG) for childbirth risk prognosis at 7–8 week of gestation because a previous child, a six-year-old boy, has congenital aniridia, glaucoma, retinal detachment, severe psychomotor delay, and lack of speech and has had several ophthalmic surgeries. The affected child had been previously tested for PAX6 mutations and 11p13 copy number variations, which revealed no changes. Considering the lack of pathogenic changes and precise diagnosis for the affected boy, NGS sequencing of clinically relevant genes was performed for the ongoing pregnancy; it revealed a novel hemizygous substitution NM_000266.3(NDP):c.385G > T, p.(Glu129*), in the NDP gene, which is associated with Norrie disease (OMIM #310600). Subsequent Sanger validation of the affected boy and his mother confirmed the identified substitution inherited in X-linked recessive mode. Amniotic fluid testing revealed the fetus was hemizygous for the variant and lead to the decision of the family to interrupt the pregnancy. Complications which developed during the termination of pregnancy required hysterectomy due to medical necessity.

Conclusions
Clinical polymorphism of hereditary ophthalmic pathology can severely complicate establishment of an exact diagnosis and make it time- and cost-consuming. NGS appears to be the method-of-choice in complicated cases, and this could substantially hasten the establishment of a diagnosis and genetic risk estimation.
Deep vein thrombosis inhibitor may play a therapeutic role in post-stroke patients
Authors: Xiang Xixi , Yuan Di , Kong Peiyan , Chen Ting , Yao Han , Lin Shijia , Zhang Xi , Cao Hongbao 
Published: October 2020

AbstractBackgroundDeep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke.Methodswe firstly conducted large-scale literature based disease-gene relationship data analysis to explore the genes implicated with DVT and stroke. Further, a mega-analysis was conducted for each of these genes that were linked to DVT but not stroke, using 11 independent stroke RNA expression datasets (176 stroke cases and 102 healthy controls). Then, a multiple linear regression (MLR) model was employed to study possible influential factors on the gene expression levels in stroke. After that, a functional pathway analysis was performed to identify the potential biological linkage between stroke and the target genes suggested by mega-analysis.ResultsOver 81.10% genes implicated with DVT also suggested an association with stroke. Among the 24 DVT-specific genes, one DVT-inhibiting gene,SP1, presented significantly increased expression in stroke (LFC = 1.34,p-value = 0.0045). Pathway analysis showed thatSP1may play a therapeutic role in post-stroke patients by promoting multiple of stroke-inhibitors. Moreover, geographical region was indicated as an influential factor on the expression levels ofSP1in stroke samples (p-value = 0.037).ConclusionOur results suggested that DVT inhibitorSP1could be a novel therapeutic target gene for post-stroke treatment. Further study of the potential relations betweenSP1and stroke was guaranteed.
Disparities in cervical cancer screening participation in Iran: a cross-sectional analysis of the 2016 nationwide STEPS survey
Authors: Amin Rozhin , Kolahi Ali-Asghar , Jahanmehr Nader , Abadi Ali-Reza , Sohrabi Mohammad-Reza 
Published: October 2020

Abstract
Background
One of the most important concerns in every healthcare system is the elimination of disparities in health service utilization and achievement of health equity. This study aimed to investigate the disparities in cervical cancer screening participation in Iran.

Methods
A cross-sectional study was conducted using data from the National Non-Communicable Risk Factors Survey in 2016 (STEPs 2016). Data on cervical cancer screening in addition to demographic and socio-economic factors from 15,975 women aged 18 and above were analyzed. The distribution of surveyed women with regard to cervical cancer screening practice was described. Chi square and logistic regression were used to assess the association of demographic and socio-economic factors with cervical cancer screening participation.

Results
Overall, 52.1% of women aged 30–59 years, had undergone cervical cancer screening at least once in their lifetime. Participation rate in cervical cancer screening programs varied between provinces; ranging from 7.6% in Sistan and Baluchestan to 61.2% in Isfahan. Single marital status, illiteracy, being employed, and having no insurance coverage were associated with lower participation. Age and area of residence were insignificant predictors for participating in cervical cancer screening program. Analysis of the cervical cancer uptake rates across the socio-economic levels revealed that the service is less utilised by high income groups.

Conclusions
Participation in cervical cancer screening program in Iran is not optimal and could be improved. With regard to the distribution of cervical cancer screening practice, social and geographical disparities indicate the need for further research and more comprehensive strategies in order to reduce them.
Haemoptysis as the first presentation of COVID-19: a case report
Authors: Peys Elise , Stevens Dieter , Weygaerde Yannick Vande , Malfait Thomas , Hermie Laurens , Rogiers Philippe , Depuydt Pieter , Van Braeckel Eva 
Published: October 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that profoundly challenges healthcare systems all over the world. Fever, cough and fatigue are the most commonly reported clinical symptoms.

Case presentation
A 58-year-old man presented at the emergency department with acute onset haemoptysis. On the fifth day after admission, he developed massive haemoptysis. Computed tomography (CT) angiography of the chest revealed alveolar haemorrhage, more prominent in the left lung. Flexible bronchoscopy confirmed bleeding from the left upper lobe, confirmed by a bronchial arteriography, which was successfully embolized. Nasopharyngeal swabs (NPS) tested for SARS-CoV-2 using real-time polymerase chain reaction (RT-PCR) repeatedly returned negative. Surprisingly, SARS-CoV-2 was eventually detected in bronchoalveolar lavage (BAL) fluid.

Conclusions
Life-threatening haemoptysis is an unusual presentation of COVID-19, reflecting alveolar bleeding as a rare but possible complication. This case emphasises the added value of bronchoscopy with BAL in the diagnostic work-up in case of high clinical suspicion and negative serial NPS in patients presenting with severe symptoms.
“Can virtue be taught?”: a content analysis of medical students’ opinions of the professional and ethical challenges to their professional identity formation
Authors: Hawking Michael , Kim Jenny , Jih Melody , Hu Chelsea , Yoon John D. 
Published: October 2020

Abstract
Background
Efforts have begun to characterize the ethical and professional issues encountered by medical students in their clinical years. By applying previously identified taxonomies to a national sample of medical students, this study seeks to develop generalizable insights that can inform professional identity formation across various clerkships and medical institutions.

Methods
In a national survey of medical students, participants answered an open-ended survey item that asked them to describe a clinical experience involving an ethical or professional issue. We conducted a content analysis with these responses using the Kaldjian taxonomy of ethical and professionalism themes in medical education through an iterative, consensus-building process. Noting the emerging virtues-based approach to ethics and professionalism, we also reexamined the data using a taxonomy of virtues.

Results
The response rate to this survey item was 144 out of 499 eligible respondents (28.9%). All 144 responses were successfully coded under one or more themes in the original taxonomy of ethical and professional issues, resulting in a total of 173 coded responses. Professional duties was the most frequently coded theme (29.2%), followed by Communication (26.4%), Quality of care (18.8%), Student-specific issues of moral distress (16.7%), Decisions regarding treatment (16.0%), and Justice (13.2%). In the virtues taxonomy, 180 total responses were coded from the 144 original responses, and the most frequent virtue coded was Wisdom (23.6%), followed by Respectfulness (20.1%) and Compassion or Empathy (13.9%).

Conclusions
Originally developed from students’ clinical experiences in one institution, the Kaldjian taxonomy appears to serve as a useful analytical framework for categorizing a variety of clinical experiences faced by a national sample of medical students. This study also supports the development of virtue-based programs that focus on cultivating the virtue of wisdom in the practice of medicine.
Computer-based cognitive rehabilitation program GRADIOR for mild dementia and mild cognitive impairment: new features
Authors: Franco-Martín Manuel A. , Diaz-Baquero Angie A. , Bueno-Aguado Yolanda , Cid-Bartolomé María T. , Parra Vidales Esther , Perea Bartolomé María V. , de la Torre Díez Isabel , van der Roest Henriëtte G. 
Published: October 2020

Abstract
Background
The growing number of older people and, with it, the increase of neurological impairments such as dementia has led to the implementation of the use of computer programs for cognitive rehabilitation in people with dementia. For 20 years, we have been developing the GRADIOR cognitive rehabilitation program and conducted several studies associated with its usability and effectiveness. This paper describes the development of the latest version of the GRADIOR computer-based cognitive rehabilitation program for people with different neurological etiologies, especially mild cognitive impairment and mild dementia.

Results
GRADIOR is a program that allows cognitive evaluation and rehabilitation of people affected by cognitive impairment. The new version of GRADIOR is characterized by a structure that is dynamic and flexible for both user and therapist, consisting of: Clinical Manager, Clinical History Manager, Treatment Manager and Report Manager. As a structure based on specific requirements, GRADIOR includes a series of modalities and sub-modalities, each modality comprising a series of exercises with different difficulty levels.

Discussion
Previous studies associated with earlier versions of GRADIOR have allowed the development of a new version of GRADIOR. Taking into account aspects associated with user experience, usability and effectiveness. Aspects that have made it possible to achieve a program that can meet the needs of older people with dementia.
Identifying frailty in trials: an analysis of individual participant data from trials of novel pharmacological interventions
Authors: Hanlon Peter , Butterly Elaine , Lewsey Jim , Siebert Stefan , Mair Frances S. , McAllister David A. 
Published: October 2020

Abstract
Background
Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD).

Methods
We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42–65 years) using individual-level participant data. Participants with a FI > 0.24 were considered ‘frail’. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex, and disease severity. In negative binomial regression, we modelled serious adverse event rates on FI and combined results for each index condition in a random-effects meta-analysis.

Results
All trials included frail participants: prevalence 7–21% in T2DM trials, 33–73% in RA trials, and 15–22% in COPD trials. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21–1.75), 1.45 (1.13–1.87), and 1.99 (1.43–2.76) for T2DM, RA, and COPD, respectively.

Conclusion
The upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.
Noninvasive prenatal paternity determination using microhaplotypes: a pilot study
Authors: Wang Jaqueline Yu Ting , Whittle Martin R. , Puga Renato David , Yambartsev Anatoly , Fujita André , Nakaya Helder I. 
Published: October 2020

Abstract
Background
The use of noninvasive techniques to determine paternity prenatally is increasing because it reduces the risks associated with invasive procedures. Current methods, based on SNPs, use the analysis of at least 148 markers, on average.

Methods
To reduce the number of regions, we used microhaplotypes, which are chromosomal segments smaller than 200 bp containing two or more SNPs. Our method employs massively parallel sequencing and analysis of microhaplotypes as genetic markers. We tested 20 microhaplotypes and ascertained that 19 obey Hardy–Weinberg equilibrium and are independent, and data from the 1000 Genomes Project were used for population frequency and simulations.

Results
We performed simulations of true and false paternity, using the 1000 Genomes Project data, to confirm if the microhaplotypes could be used as genetic markers. We observed that at least 13 microhaplotypes should be used to decrease the chances of false positives. Then, we applied the method in 31 trios, and it was able to correctly assign the fatherhood in cases where the alleged father was the real father, excluding the inconclusive results. We also cross evaluated the mother-plasma duos with the alleged fathers for false inclusions within our data, and we observed that the use of at least 15 microhaplotypes in real data also decreases the false inclusions.

Conclusions
In this work, we demonstrated that microhaplotypes can be used to determine prenatal paternity by using only 15 regions and with admixtures of DNA.