Machine learning enhances genotoxicity assessment using MultiFlow® DNA damage assay.

Genotoxicity is a critical determinant for assessing the safety of pharmaceutical drugs, their metabolites, and impurities. Among genotoxicity tests, mechanistic assays such as the MultiFlow® DNA damage assay (MFA) allows the investigations on mode of action (MoA) of DNA damage through four mechanistic markers recorded at two time points. Previous studies have shown that machine learning (ML) can enhance precision on classifying the MoA of genotoxicants.

Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription.

Transcripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis.

A Stable Carbon-Centered Radical Showing Six Amphoteric Redox States.

An air- and moisture-stable hydrocarbon radical with four six- and three five-membered rings alternately fused to a heptacycle was obtained by ortho fusion in a suitably ortho,ortho'-substituted diphenylfluorene and subsequent re-establishment of the conjugation. The radical was obtained in five consecutive steps from commercially available starting materials with a total yield of 34 %; key steps are Suzuki couplings and cyclizing SAr reactions. Mesityl substituents at the five-membered rings ensure the stability of the radical.

Subtle signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with reduced cognitive function: results from the Hamburg City Health Study.

Background: Atrial fibrillation is associated with cognitive dysfunction. Atrial cardiomyopathy has been correlated with both entities. We aimed to characterize the association of echocardiographic parameters of atrial cardiomyopathy with cognitive function and cerebral changes.

One-year ecological momentary assessment of alcohol use, mood, and stress among individuals with alcohol use disorder during SARS-CoV-2 pandemics: a gender-specific reflection.

Alcohol consumption (AC) is a leading risk factor for death, morbidity, and disability worldwide. Gender-specific differences in AC and its moderators, which may serve as markers for preventing severe alcohol use disorders (AUD), showed inconsistent results. Additionally, the impact of COVID-19-related lockdowns on these differences remains unclear.

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study.

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed.

Screening for Cognitive Decline by Lay Navigators: A Scoping Review.

Innovative ways of screening for cognitive decline are urgently needed to increase detection and access to early treatment, particularly for those at highest risk for morbidity and mortality. The aim of this scoping review was to identify how cognitive screening is conducted within primary care and other clinical settings, specifically focusing on the use of lay navigators. Using Arksey and O'Malley's framework for scoping reviews, inclusive of collaborators' feedback, we included English-language research articles published after 2010 and identified ten articles.

Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow.

Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia-neuronal activity-to-vascular response-the mechanical consequences of hyperemia have gone largely unexplored.

Experiences in Recruitment for Hispanic, Non-Hispanic Black, and Other Non-White Cancer Survivors Through Community Outreach and Other Targeted Approaches.

Objectives: Recruitment of racial/ethnic underserved populations in oncology research is essential to address health disparities. This article presents strategies and lessons learned from community outreach and other approaches for recruiting non-Hispanic Black, Hispanic, and other non-White survivors of cancer into a pilot study that investigated biopsychosocial determinants of health behaviors.

Methods: We critically examined the participant recruitment approaches to explore challenges and successful strategies and develop recommendations for future studies.

Evaluation of the nitrosamine impurities of ACE inhibitors using computational, in vitro, and in vivo methods demonstrate no genotoxic potential.

Evaluation and mitigation of the potential carcinogenic risks associated with nitrosamines in marketed pharmaceutical products are areas of interest for pharmaceutical companies and health authorities alike. Significant progress has been made to establish acceptable intake (AI) levels for N-nitrosamine drug substance-related impurities (NDSRIs) using SAR, however some compounds require experimental data to support derivation of a recommended AI. Many angiotensin-converting enzyme inhibitors, identified by the suffix "pril," have secondary amines that can potentially react to form nitrosamines.

Estimation of 100 m root zone soil moisture by downscaling 1 km soil water index with machine learning and multiple geodata.

Root zone soil moisture (RZSM) is crucial for agricultural water management and land surface processes. The 1 km soil water index (SWI) dataset from Copernicus Global Land services, with eight fixed characteristic time lengths (T), requires root zone depth optimization (T) and is limited in use due to its low spatial resolution. To estimate RZSM at 100-m resolution, we integrate the depth specificity of SWI and employed random forest (RF) downscaling.

Acute hepatitis E virus infection presenting as meningo-encephalitis.

Background: Acute hepatitis E infection (HEV), with its high incidence in Europe, should be considered as a differential diagnosis of acute viral hepatitis and can in some cases manifest with pronounced neurological symptoms.

Clinical Case: We report on a 33-year-old female patient with severe arthralgia, myalgia, headache and psychomotor deterioration. Laboratory analyses showed elevated transaminases without signs of cholestasis.

The Interplay of Psycho-Social Determinants on Quality of Life and Health Behaviors Among Hispanic, Non-Hispanic Black Cancer Survivors.

Objectives: This study aimed to explore psycho-social factors (i.e., socio-demographics, health insurance, stress) associated with Quality of life (QOL) and the degree to which self-reported access to healthcare and health behaviors (i.

Cutaneous tissue samples show significant shrinkage during histopathological work-up: a real-world study.

Background: Excision and histological examination of cutaneous neoplasms are very common diagnostic and therapeutic procedures in dermatological practice. There are often discrepancies between tissue seize in vivo and after histopathological work-up. This may raise questions according to tumor sizes or safety margins.

Proprotein Convertase Subtilisin/Kexin Type 9 Induction in COVID-19 Is Poorly Associated with Disease Severity and Cholesterol Levels.

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease.

Hepatitis E virus infection in immunosuppressed patients and its clinical manifestations.

Background & Aims: Hepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections.

Patient perspectives on cancer care during COVID-19: A qualitative study.

Purpose: The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time.

Methods: We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022.

Multiethnic Perspectives of Shared Decision-Making in Hypertension: A Mixed-Methods Study.

Background: Shared decision-making (SDM) has the potential to improve hypertension care quality and equity. However, research lacks diverse representation and evidence about how race and ethnicity affect SDM. Therefore, this study aims to explore SDM in the context of hypertension management.

Exploration of Stress and Inflammatory Biomarkers Among Non-Hispanic Black and Hispanic Cancer Survivors.

Objectives: To evaluate associations among social determinants of health (SDOH), stress, interleukin-6 (IL-6), and quality of life among non-Hispanic Black and Hispanic cancer survivors.

Sample & Setting: Individuals who had completed cancer treatment and did not identify as White (N = 46) were recruited through community partnerships in western Massachusetts and a state cancer registry.

Methods & Variables: This descriptive cross-sectional study used questionnaires and morning salivary samples to collect data between June 2022 and September 2023.

Online communication skill training of patients with cancer: A test of the behavioral intention predictive framework for communication skills.

Objective: To assess the Behavioral Intention Predictive Framework's utility in explaining variation in cancer patients' strong behavioral intention (SBI) to use LEAPS (Listen, Educate, Assess, Partner, Support) communication skills after viewing training videos.

Methods: Ninety-eight patients were enrolled through anonymized online platforms to view LEAPS training videos, complete background and communication questionnaires and report their SBI to use LEAPS skills.

Results: On average, patients indicated SBI to use 6 of 13 skills and 46% of patients expressed SBI across individual skills.

Proof of infectivity of hepatitis E virus particles from the ejaculate of chronically infected patients.

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36-67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100-fold higher compared to the serum, while in two patients, the viral load was more than 10-fold lower.

Soluble CD46 as a diagnostic marker of hepatic steatosis.

Background: The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) incurs substantial morbidity, mortality and healthcare costs. Detection and clinical intervention at early stages of disease improves prognosis; however, we are currently limited by a lack of reliable diagnostic tests for population screening and monitoring responses to therapy. To address this unmet need, we investigated human invariant Natural Killer T cell (iNKT) activation by fat-loaded hepatocytes, leading to the discovery that circulating soluble CD46 (sCD46) levels accurately predict hepatic steatosis.

Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers' sleep, oxygen saturation and heart rate on long-haul flights.

Background: Passengers on long-haul flights frequently consume alcohol. Inflight sleep exacerbates the fall in blood oxygen saturation (SpO) caused by the decreased oxygen partial pressure in the cabin. We investigated the combined influence of alcohol and hypobaric hypoxia on sleep, SpO and heart rate.