bluuebunny/crossref_metadata_2025 huggingface dataset:
Dangerous fields: Existentiality, humanity and musical creativity in German refugee camps
Authors: Pistrick Eckehard
Published: October 2020

This article focuses on the role of music in the context of humanitarian and existential crisis. It argues that the ethnographic field of the refugee camp is everything else than an unproductive space, a “waiting room” of the undesirables, an in-between space where social lives are suspended and where cultural life ceases to exist. It presents in a first part the particular spatial and temporal dimensions of a specific refugee reception center in Germany, in which the author has both volunteered for 6 months organizing music room sessions, and in which he has worked as an engaged anthropologist in the framework of a 4-month grassroots music theater project. In a second part, individual biographies of musicking asylum-seekers are presented: seen from the standpoint of an anthropology of emotions and an anthropology of absence, it will be discussed in which way the experience of marginalization, social exclusion and continuous waiting has influenced the texts and musical pieces created by them. In more general terms, this article looks at the ethnomusicologists’ dilemma of whether and how to make visible and audible such cultural creativity in an empathetic way without detaching it from the precarious and existential situations under which it unfolds.
Romosozumab: A Novel Agent in the Treatment for Postmenopausal Osteoporosis
Authors: Miller Shannon A. , St. Onge Erin Lyn , Whalen Karen L.
Published: October 2020

Objective: To review the safety and efficacy of romosozumab (Evenity) in the treatment of osteoporosis in women. Data Sources: An English-language search of PubMed and Medline (1966 to August 2020) was conducted using the keywords romosozumab, sclerostin inhibitor, AMG785, and osteoporosis. Manufacturer prescribing information, abstracts, fda.gov, and ClinicalTrials.gov data were incorporated for additional materials. In addition, a review of bibliographies of retrieved articles was performed to identify additional references. Study Selection/Data Extraction: Articles selected included those that described clinical studies of pharmacokinetics, efficacy, or safety of romosozumab. Data Synthesis: Romosozumab is a human monoclonal antibody that inhibits the action of sclerostin and is the first agent in its class to reach Phase III trials. Significant increases in bone mineral density and decreases in vertebral and hip fractures are demonstrated in Phase III trials. Favorable results led to its marketing approval in several countries. Major adverse cardiac events were observed in one clinical trial. Other adverse effects include arthralgia, headache, and injection site reactions. Place in Therapy: Romosozumab is the first agent to inhibit bone resorption and stimulate bone formation. Romosozumab should be reserved for postmenopausal women at highest risk for fracture and should be followed by an anti-resportive agent to maintain or further increase bone mineral density. This injectable agent should not be considered for women with a history of or at high risk of cardiovascular disease.
Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Ueno Hiroo , Yoshida Kenichi , Shiozawa Yusuke , Nannya Yasuhito , Iijima-Yamashita Yuka , Kiyokawa Nobutaka , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Isobe Tomoya , Seki Masafumi , Kimura Shunsuke , Makishima Hideki , Nakagawa Masahiro M. , Kakiuchi Nobuyuki , Kataoka Keisuke , Yoshizato Tetsuichi , Nishijima Dai , Deguchi Takao , Ohki Kentaro , Sato Atsushi , Takahashi Hiroyuki , Hashii Yoshiko , Tokimasa Sadao , Hara Junichi , Kosaka Yoshiyuki , Kato Koji , Inukai Takeshi , Takita Junko , Imamura Toshihiko , Miyano Satoru , Manabe Atsushi , Horibe Keizo , Ogawa Seishi , Sanada Masashi
Published: October 2020

Recent genetic studies using high-throughput sequencing have disclosed genetic alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes have not been fully investigated. To address this, we comprehensively examined genetic alterations and their prognostic impact in a large series of pediatric B-ALL cases. We performed targeted capture sequencing in a total of 1003 pediatric patients with B-ALL from 2 Japanese cohorts. Transcriptome sequencing (n = 116) and/or array-based gene expression analysis (n = 120) were also performed in 203 (84%) of 243 patients who were not categorized into any disease subgroup by panel sequencing or routine reverse transcription polymerase chain reaction analysis for major fusions in B-ALL. Our panel sequencing identified novel recurrent mutations in 2 genes (CCND3 and CIC), and both had positive correlations with ETV6-RUNX1 and hypodiploid ALL, respectively. In addition, positive correlations were also newly reported between TCF3-PBX1 ALL with PHF6 mutations. In multivariate Cox proportional hazards regression models for overall survival, TP53 mutation/deletion, hypodiploid, and MEF2D fusions were selected in both cohorts. For TP53 mutations, the negative effect on overall survival was confirmed in an independent external cohort (n = 466). TP53 mutation was frequently found in IGH-DUX4 (5 of 57 [9%]) ALL, with 4 cases having 17p LOH and negatively affecting overall survival therein, whereas TP53 mutation was not associated with poor outcomes among NCI (National Cancer Institute) standard risk (SR) patients. A conventional treatment approach might be enough, and further treatment intensification might not be necessary, for patients with TP53 mutations if they are categorized into NCI SR.
Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab
Authors: Krishnan Amrita , Adhikarla Vikram , Poku Erasmus K. , Palmer Joycelynne , Chaudhry Ammar , Biglang-awa Van Eric , Bowles Nicole , Nathwani Nitya , Rosenzweig Michael , Sahebi Firoozeh , Karanes Chatchada , Simpson Jennifer , Sanchez James F. , Yamauchi Dave , Parayno Maria , Chowdhury Arnab , Caserta Enrico , Marcucci Guido , Rockne Russell , Wu Anna M. , Wong Jeffrey , Forman Stephen J. , Colcher David , Yazaki Paul , Shively John , Pichiorri Flavia
Published: October 2020

18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.
Effective control ofStaphylococcus aureuslung infection despite tertiary lymphoid structure disorganisation
Authors: Regard Lucile , Martin Clémence , Teillaud Jean-Luc , Lafoeste Hélène , Vicaire Hugues , Ladjemi Maha Zohra , Ollame-Omvane Emilie , Sibéril Sophie , Burgel Pierre-Régis
Published: October 2020

Background

Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection withStaphylococcus aureus, but their roles remain elusive. The present study sought to examine the effects of B- and/or T-cell depletion onS. aureusinfection and TLS development (lymphoid neogenesis) in mice.

Methods

C57Bl/6 mice were pre-treated with 1) an anti-CD20 monoclonal antibody (mAb) (B-cell depletion) or 2) an anti-CD4 and/or an anti-CD8 mAb (T-cell depletion) or 3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B- and T-cell depletion) or 4) isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containingS. aureus(106 CFU per mouse). 14 days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.

Results

14 days afterS. aureus-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pre-treated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20+B-lymphocytes had no effect on CD3+T-lymphocyte infiltration, whereas CD4+/CD8+T-cell depletion markedly reduced CD20+B-cell infiltration. Depletion of CD4+or CD8+T-cells separately had limited effect on B-cell infiltration, but led to the absence of germinal centres.

Conclusion

TLS disorganisation is not associated with loss of infection control in mice persistently infected withS. aureus.
NIMBus: a negative binomial regression based Integrative Method for mutation Burden Analysis
Authors: Zhang Jing , Liu Jason , McGillivray Patrick , Yi Caroline , Lochovsky Lucas , Lee Donghoon , Gerstein Mark
Published: October 2020

Background

Identifying frequently mutated regions is a key approach to discover DNA elements influencing cancer progression.
However, it is challenging to identify these burdened regions due to mutation rate heterogeneity across the genome and across different individuals. Moreover, it is known that this heterogeneity partially stems from genomic confounding factors, such as replication timing and chromatin organization. The increasing availability of cancer whole genome sequences and functional genomics data from the Encyclopedia of DNA Elements (ENCODE) may help address these issues.

Results

We developed a negative binomial regression-based Integrative Method for mutation Burden analysiS (NIMBus). Our approach addresses the over-dispersion of mutation count statistics by (1) using a Gamma–Poisson mixture model to capture the mutation-rate heterogeneity across different individuals and (2) estimating regional background mutation rates by regressing the varying local mutation counts against genomic features extracted from ENCODE. We applied NIMBus to whole-genome cancer sequences from the PanCancer Analysis of Whole Genomes project (PCAWG) and other cohorts. It successfully identified well-known coding and noncoding drivers, such as TP53 and the TERT promoter. To further characterize the burdening of non-coding regions, we used NIMBus to screen transcription factor binding sites in promoter regions that intersect DNase I hypersensitive sites (DHSs). This analysis identified mutational hotspots that potentially disrupt gene regulatory networks in cancer. We also compare this method to other mutation burden analysis methods.

Conclusion

NIMBus is a powerful tool to identify mutational hotspots. The NIMBus software and results are available as an online resource at github.gersteinlab.org/nimbus.
PyGNA: a unified framework for geneset network analysis
Authors: Fanfani Viola , Cassano Fabio , Stracquadanio Giovanni
Published: October 2020

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

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

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

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

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

Background

Deep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke.

Methods

we 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.

Results

Over 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).

Conclusion

Our 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

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

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

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

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

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

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.
Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial
Authors: Maltais F. , Naya I. P. , Vogelmeier C. F. , Boucot I. H. , Jones P. W. , Bjermer L. , Tombs L. , Compton C. , Lipson D. A. , Kerwin E. M.
Published: October 2020

Background

Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD.

Methods

The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates.

Results

At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59–74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day.

Conclusions

In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome.

Funding

GlaxoSmithKline (study number 201749 [NCT03034915]).
Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients
Authors: Wang Jun , Zhang Hongliang , Sun Xin , Wang Xiaofang , Ren Tingting , Huang Yi , Zhang Ranxin , Zheng Bingxin , Guo Wei
Published: October 2020

Background

Recent studies indicated that exosomal programmed death-ligand 1 (PD-L1) derived from cancers could induce immunosuppression and tumor pathogenesis. However, it is unclear how exosomes influence osteosarcoma (OS) progression and whether PD-L1 also exists in serum exosomes (Sr-exosomes) of patients with osteosarcoma. We examined serum exosomes from 70 OS patients, 9 patients with benign tumors and 22 healthy donors. OS-derived exosomes were functionally evaluated in vivo and in vitro.

Results

The characteristics of exosomes derived from OS patient serum and OS cell lines were confirmed by several methods. We found OS patients had a higher level of exosomal PD-L1 compared to healthy donors. Meanwhile, OS patients with pulmonary metastasis also showed a relatively higher level of exosomal PD-L1 than patients without metastasis. Next, bioinformatic analysis demonstrated that Sr-exosomes isolated from OS patients may involve in the important process of immune function and cancer pathogenesis for OS patients. Co-expression network centered with PD-L1 among Sr-exosomal differently expressed mRNA demonstrated exosomal N-cadherin had a close relationship with exosomal PD-L1 expression. Then, we confirmed higher level of Sr-exosomal N-cadherin in OS patients with pulmonary metastasis compared to ones without metastasis. Furthermore, we elucidated osteosarcoma-derived exosomes and exosomal-PD-L1 promoted the pulmonary metastasis in metastatic models. ROC (Receiver Operating Characteristic Curve) analysis showed AUC (Area Under Curve) of 0.823 for exosomal PD-L1, 0.806 for exosomal N-cadherin and 0.817 for exosomal N-cadherin/E-cadherin to distinguish OS patients with pulmonary metastasis from ones without metastasis.

Conclusions

Osteosarcoma stimulates pulmonary metastasis by releasing exosomes, that carry PD-L1 and N-cadherin. Detection of exosomal PD-L1 and N-cadherin from serum of OS patients may predict pulmonary metastasis progression for OS patients.
Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) in mainland China: an investigation of reliability, validity, and responsiveness
Authors: Zhou Feifei , Li Shuyang , Zhang Yilong , Zhao Yanbin , Ju Kevin L. , Zhang Fengshan , Pan Shengfa , Sun Yu
Published: October 2020

Background

The aim of this study is to investigate the reliability, validity, and responsiveness of JOACMEQ for CSM patients in mainland China.

Methods

A retrospective review was performed on 91 patients with CSM in our hospital from March 2015 to June 2015. Patients completed the JOACMEQ, the mJOA and the SF-36 questionnaires during the process. Cronbach's α was used to evaluate the internal consistency reliability, and test–retest reliability was checked. An exploratory factor analysis was used to determine the correlations among the JOACMEQ questions and the construct validity. The concurrent validity was assessed by Spearman correlation coefficient. The internal responsiveness was determined by effect sizes and standardized response means. External responsiveness was determined by the area under the receiver operating characteristic curve on the basis of the Youden Index.

Results

The mean age of patients was 57.61 years old. The mean follow-up was 24 months. JOACMEQ showed a good internal consistency (Cronbach's α, 0.897). Test–retest reliability showing good result (Pearson's correlation, 0.695–0.905). Our data were amenable to factor analysis (KMO = 0.816, Bartlett's test, χ2(45) = 1199.99, p < 0.001), and five factors above 1 were strongly loaded and clustered for each of the five factors. Comparing the scales preoperative to those 2 years postoperative, the average scores of the subscales all increased, and both the ES and SRM showing satisfied responsiveness. In external responsiveness analysis, the recovery rate a appeared to be most responsive to post-operative improvement.

Conclusions

The Simplified Chinese version of JOACMEQ was well-developed with great reliability and sensitive responsiveness. Our study demonstrated that JOACMEQ has content psychometric properties to identify postoperative improvements in CSM patients.
Correction to: Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma
Authors: Lu Chenying , Fang Shiji , Weng Qiaoyou , Lv Xiuling , Meng Miaomiao , Zhu Jinyu , Zheng Liyun , Hu Yumin , Gao Yang , Wu Xulu , Mao Jianting , Tang Bufu , Zhao Zhongwei , Huang Li , Ji Jiansong
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer
Authors: Muresu Narcisa , Sotgiu Giovanni , Saderi Laura , Sechi Illari , Cossu Antonio , Marras Vincenzo , Meloni Marta , Martinelli Marianna , Cocuzza Clementina , Tanda Francesco , Piana Andrea
Published: October 2020

Background

Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases.

Methods

An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression.

Results

HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives.

Discussion

The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins.

Conclusion

HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.
Ethnobotanical survey of wild edible plants used by Baka people in southeastern Cameroon
Authors: Billong Fils Pascal Eric , Afiong Nana Natacha , Betti Jean Lagarde , Farick Njimbam Oumar , Tientcheu Womeni Stéphanie , Ávila Martin Eva , Ros Brull Guillermo , Okale Robert , Fa Julia E. , Funk Stephan M.
Published: October 2020

Background

Forest inhabitants worldwide, and indigenous people especially, have depended for generations on plants and animals harvested in these ecosystems. A number of Baka hunter-gatherer populations in south-eastern Cameroon became sedentarised in the 1950s, but still rely on hunting and gathering to meet their basic needs. The use of wild edible plants (WEP) by these communities remains largely undocumented. In this study, we record the diversity of WEP used by Baka people in dense rainforests in the Mintom region. The area still contains relatively undisturbed forest expanses, just south of the Dja Biosphere Reserve, one of the most important protected areas in the Congo Basin.

Methods

We conducted two ethnobotanical surveys in 2019 in four villages on the Mintom road. In the first survey, we interviewed a total of 73 individuals to determine WEP usage. In our second survey, we specifically quantified WEP harvested and consumed daily in a number of households over a 2-week period during the major rainy season, when use of forest products is highest. Specimens of all recorded plants were collected and identified at the National Herbarium of Cameroon.

Results

We documented 88 plant species and 119 unique species/plant organ/recipes in 1519 different citations. A total of 61 genera and 43 families were noted. Excluding 14 unidentified wild yam species, 17 WEP species had not been reported in previous ethnobotanical surveys of the Baka. Our results showed that cultivated starchy plant foods make up a significant proportion of our study population’s daily nutritional intake.

Conclusions

A high diversity of WEP is consumed by the studied Baka communities. The study area is likely to be significant in terms of WEP diversity since 18 out of the 30 “key” non-timber forest products, NTFP, in Cameroon were mentioned. Documentation of the use of WEP by indigenous communities is vital to ensure the continuity of traditional knowledge and future food security.