COVID-19 severity gradient differentially dysregulates clinically relevant drug processing genes in nasopharyngeal swab samples.

AIM: Understanding how COVID-19 impacts the expression of clinically relevant drug metabolizing enzymes and membrane transporters (DMETs) is vital for addressing potential safety and efficacy concerns related to systemic and peripheral drug concentrations. This study investigates the impact of COVID-19 severity on DMETs expression and the underlying mechanisms to inform the design of precise clinical dosing regimens for affected patients. METHODS: Transcriptomics analysis of 102 DMETs, 10 inflammatory markers, and 12 xenosensing regulatory genes was conducted on nasopharyngeal swabs from 50 SARS-CoV-2 positive (17 outpatients, 16 non-ICU, and 17 ICU) and 13 SARS-CoV-2 negative individuals, clinically tested through qPCR, in the Greater Toronto area from October 2020 to October 2021. RESULTS: We observed a significant differential gene expression for 42 DMETs, 6 inflammatory markers, and 9 xenosensing regulatory genes. COVID-19 severity was associated with the upregulation of AKR1C1, MGST1, and SULT1E1, and downregulation of ABCC10, CYP3A43, and SLC29A4 expressions. Altogether, SARS-CoV-2-positive patients showed an upregulation in CYP2C9, CYP2C19, AKR1C1, SULT1B1, SULT2B1, and SLCO4A1 and downregulation in FMO5, MGST3, ABCC5, and SLCO4C1 compared with SARS-CoV-2 negative individuals. These dysregulations were associated with significant changes in the expression of inflammatory and xenosensing regulatory genes driven by the disease. GSTM3, PPARA, and AKR1C1 are potential biomarkers of the observed DMETs dysregulation pattern in nasopharyngeal swabs of outpatients, non-ICU, and ICU patients, respectively. CONCLUSION: The severity of COVID-19 is associated with the dysregulation of DMETs involved in processing commonly prescribed drugs, suggesting potential disease-drug interactions, especially for narrow therapeutic index drugs.

Metatranscriptomic RNA-Seq Data Analysis of Virus-Infected Host Cells.

RNA sequencing (RNA-seq) analysis of virus-infected host cells enables researchers to study a wide range of phenomena involving host-virus interactions. This includes genomic analysis of the viral population itself, as well as analysis of the transcriptional dynamics of the virus and host during infection. In this chapter, we provide a guide for researchers interested in performing RNA-seq data analysis of virus-infected host cells or cell lines. We outline several bioinformatic protocols for quantifying viral abundance, assembling viral genomes from mixed samples, and performing differential expression analysis, among other common workflows. These workflows can be used as starting points for researchers aiming to analyze RNA-seq datasets of mixed samples containing both host and viral RNA, such as virus-infected cell lines or clinical samples.

Assessment of the well-being of significant others of cardiothoracic surgeons.

OBJECTIVES: We aimed to evaluate how the current working climate of cardiothoracic surgery and burnout experienced by cardiothoracic surgeons influences their spouses and significant others (SOs). METHODS: A 33-question well-being survey was developed by the American Association for Thoracic Surgery Wellness Committee and distributed by e-mail to the SOs of cardiothoracic surgeons and to all surgeon registrants of the 2020 and 2021 American Association for Thoracic Surgery Annual Meetings with a request to share it with their SO. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by χ2 or independent samples t tests, as appropriate. RESULTS: Responses from 238 SOs were analyzed. Sixty-six percent reported that the stress on their cardiothoracic surgeon partner had a moderate to severe influence on their family, and 63% reported that their partner's work demands didn't leave enough time for family. Fifty-one percent reported that their partner rarely had time for intimacy, 27% reported poor work-life balance, and 23% reported that interactions at home were usually or always not good-natured. SOs were most affected when their partner was <5 years out from training, worked in private vs academic practice, and worked longer hours. Having children, particularly younger than age 19 years, and a lack of workplace support resources further diminished well-being. CONCLUSIONS: The current work culture of cardiothoracic surgeons adversely affects their SOs, and the risk for families is concerning. These data present a major area for exploration as we strive to understand and mitigate the factors that lead to burnout among cardiothoracic surgeons.

Open Access and Article Processing Charges in Cardiology and Cardiac Surgery Journals: a Cross-Sectional Analysis

Abstract Introduction: Open access (OA) publishing often requires article processing charges (APCs). While OA provides opportunities for broader readership, authors able to afford APCs are more commonly associated with well-funded, high-income country institutions, skewing knowledge dissemination. Here, we evaluate publishing models, OA practices, and APCs in cardiology and cardiac surgery. Methods: The InCites Journal Citation Reports 2019 directory by Clarivate Analytics was searched for "Cardiac and Cardiovascular Systems" journals. Sister journals of included journals were identified. All journals were categorized as predominantly cardiology or cardiac surgery. Publishing models, APCs, and APC waivers were defined for all journals. Results: One hundred sixty-one journals were identified (139 cardiology, 22 cardiac surgery). APCs ranged from $244 to $5,000 ($244-5,000 cardiology; $383-3,300 cardiac surgery), with mean $2,911±891 and median $3,000 (interquartile range [IQR]: $2,500-3,425) across 139 journals with non-zero available APCs ($2,970±890, median $3,000, IQR: $2,573-3,450, cardiology; $2,491±799, median $2,740, IQR: $2,300-3,000, cardiac surgery). Average APCs were $3,307±566 and median $3,250 (IQR: $3,000-3,500) for hybrid journals ($3,344±583, median $3,260, IQR: $3,000-3,690, cardiology; $2,983±221, median $2,975, IQR: $2,780-3,149, cardiac surgery) and $1,997±832 and median $2,100 (IQR: $1,404-2,538) for fully OA journals ($2,039±843, median $2,100, IQR: $1,419-2,604, cardiology; $1,788±805, median $2,000, IQR: $1,475-2,345, cardiac surgery). Waivers were available for 51 (86.4%) fully OA and 37 (37.4%) hybrid journals. Seventeen journals were fully OA without APCs, one journal did not yet release APCs, and four journals were subscription-only. Conclusion: OA publishing is common in cardiology and cardiac surgery with substantial APCs. Waivers remain limited, posing barriers for unfunded and lesser-funded researchers.