Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

A Cross-sectional Study Investigating the Oral Health Status of Adult and Elderly Swiss Community-Dwellers.

Purpose: To evaluate the oral health status of community-dwellers ≥ 45 years of age in the canton of Bern, Switzerland.

Materials And Methods: Data were collected using a questionnaire (including sociodemographic factors, medical history, oral health behaviour) and a clinical examination comprising caries, periodontal disease, oral hygiene, and prosthetic rehabilitation. χ2/Fisher's tests and Cochrane Armitage trend tests as well as a binary logistic regression were performed to assess the association between oral disease presence (i.

Elevated Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Acute Myocarditis.

Background: Neutrophil-to-lymphocyte ratio (NLR) is an easy-to-use inflammatory biomarker. Baseline NLR is independently associated with incident cardiovascular events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Crown ether functionalization boosts CO electroreduction to ethylene on copper-based MOFs.

The electroconversion of CO into ethylene (CH) offers a promising solution to environmental and energy challenges. Crown ether (CE) modification significantly enhances the CH selectivity of copper-based MOFs, improving CH faradaic efficiency (FE) in CuBTC, CuBDC, and CuBDC-NH by 3.1, 1.

An In Vivo Biostability Evaluation of ALD and Parylene-ALD Multilayers as Micro-Packaging Solutions for Small Single-Chip Implants.

Miniaturization of next-generation active neural implants requires novel micro-packaging solutions that can maintain their long-term coating performance in the body. This work presents two thin-film coatings and evaluates their biostability and in vivo performance over a 7-month animal study. To evaluate the coatings on representative surfaces, two silicon microchips with different surface microtopography are used.

Anti-HIV-1 Effect of the Fluoroquinolone Enoxacin and Modulation of Pro-Viral hsa-miR-132 Processing in CEM-SS Cells.

Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations.

Acute Effects of Passive Stretching with and Without Vibration on Hip Range of Motion, Temperature, and Stiffness Parameters in Male Elite Athletes.

: Increasing exercise intensity and performance output with superimposed vibration gains interest, especially in high-performance training. However, the additional benefit of vibration in passive stretching exercises and its mechanisms remain unclarified. : Passive stretching with (ST+V) and without (ST) vibration (20 Hz) was performed in male Olympic youth skiing athletes ( = 8, age: 17.

Can Hearing Aids Improve Physical Activity in Adults with Hearing Loss? A Feasibility Study.

: Adults with hearing loss demonstrate poorer overall health outcomes (e.g., physical health, cognitive functioning and wellbeing) and lower levels of physical activity/function compared to those without hearing loss.

Impact of Varying Sleep Pressure on Daytime Sleep Propensity in Healthy Young and Older Adults.

Fixed sleep schedules with an 8 h time in bed (TIB) are used to ensure participants are well-rested before laboratory studies. However, such schedules may lead to cumulative excess wakefulness in young individuals. Effects on older individuals are unknown.

In silico optimization of a challenging bispecific antibody chromatography step.

Mechanistic modeling of chromatographic steps is an effective tool in biopharma process development that enhances process understanding and accelerates optimization efforts and subsequent risk assessment. A relatively new model for ion exchange chromatography is the colloidal particle adsorption (CPA) formalism, which promises improved separation of material and molecule-specific parameters. This case study demonstrates a straightforward CPA modeling workflow to describe an ion exchange chromatography polishing step of a knobs-into-holes construct bispecific antibody molecule.

Greenhouse Gas Emissions and Decarbonization Potential of Global Fired Clay Brick Production.

Fired clay bricks (FCBs) are a dominant building material globally due to their low cost and simplicity of production, especially in low- and middle-income countries. With a projected rising housing demand, commensurate growth in brick demand is anticipated, the production of which could result in significant greenhouse gas (GHG) emissions. Robust models are needed to estimate brick demand and emissions to systematically address decarbonization pathways.

Simple User-Friendly Reaction Format.

Utilizing the growing wealth of chemical reaction data can boost synthesis planning and increase success rates. Yet, the effectiveness of machine learning tools for retrosynthesis planning and forward reaction prediction relies on accessible, well-curated data presented in a structured format. Although some public and licensed reaction databases exist, they often lack essential information about reaction conditions.

How Do Personality Dysfunction and Maladaptive Personality Traits Predict Time to Premature Discontinuation of Pharmacological Treatment of ADHD?

Objectives: Non-adherence to medication is common in the adult ADHD clinical group. The goal of this pre-registered study was to examine whether the DSM-5 Alternative Model of Personality Disorder (AMPD), generality personality dysfunction (LPFS-BF 2.0) or maladaptive personality traits (PID-5), can predict time to premature discontinuation of pharmacological treatment beyond other known factors.

A global review of national guidelines of post-exposure prophylaxis for the prevention of HIV.

Introduction: The World Health Organization (WHO) recommends the use of antiretroviral drugs as post-exposure prophylaxis (PEP) for preventing HIV acquisition for occupational and non-occupational exposures. To inform the development of global WHO recommendations on PEP, we reviewed national guidelines of PEP for their recommendations.

Methods: Policies addressing PEP from 38 WHO HIV priority countries were obtained by searching governmental and non-governmental websites and consulting country and regional experts; these countries were selected based on HIV burden, new HIV acquisitions and the number of HIV-associated deaths.

Dissecting AlphaFold2's capabilities with limited sequence information.

Summary: Protein structure prediction aims to infer a protein's three-dimensional (3D) structure from its amino acid sequence. Protein structure is pivotal for elucidating protein functions, interactions, and driving biotechnological innovation. The deep learning model AlphaFold2, has revolutionized this field by leveraging phylogenetic information from multiple sequence alignments (MSAs) to achieve remarkable accuracy in protein structure prediction.

Advanced electrocardiography heart age: a prognostic, explainable machine learning approach applicable to sinus and non-sinus rhythms.

Aims: An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular aging expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm.

Determinants of physical function, as measured using PROMIS PF-10a, in patients with rheumatoid arthritis: results from the international COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.

Objectives: Physical function in RA is largely influenced by multiple clinical factors, however, there is a growing body of evidence that psychological state and other comorbidities also play an essential role. Using data obtained in the COVID-19 Vaccination in Autoimmune Diseases study, an international self-reported e-survey, we aimed to explore the predictive ability of sociodemographic and clinical variables on Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS PF-10a) in RA and to investigate variation in disease activity and functional outcomes based on country-level socio-economic parameters.

Methods: Patient demographics, disease characteristics including current symptom status, functional status and treatment variables, as well as income level of the country of residence, were extracted from survey responses.

Long-term ultrasonographic changes of the canine prostate gland after castration.

Introduction: Ultrasound imaging (US) is the method of choice to assess the canine prostate gland. Whilst recent studies have documented the role of castration in the development of prostatic neoplasia, little is known about parenchymal and perfusion features of the normal and abnormal prostate in neutered dogs. No data are available concerning prostatic changes after the first 90 days following castration.

Electronic dynamics created at conical intersections and its dephasing in aqueous solution.

A dynamical rearrangement in the electronic structure of a molecule can be driven by different phenomena, including nuclear motion, electronic coherence or electron correlation. Recording such electronic dynamics and identifying its fate in an aqueous solution has remained a challenge. Here, we reveal the electronic dynamics induced by electronic relaxation through conical intersections in both isolated and solvated pyrazine molecules using X-ray spectroscopy.

Brain microstructure alterations in subjective cognitive decline: a multi-component T2 relaxometry study.

Previous research has revealed patterns of brain atrophy in subjective cognitive decline, a potential preclinical stage of Alzheimer's disease. However, the involvement of myelin content and microstructural alterations in subjective cognitive decline has not previously been investigated. This study included three groups of participants recruited from the Compostela Aging Study project: 53 cognitively unimpaired adults, 16 individuals with subjective cognitive decline and hippocampal atrophy and 70 with subjective cognitive decline and no hippocampal atrophy.

A new conceptual model for seed germination and seedling tillering of winter wheat in the field.

Seed germination is a crucial stage in plant development, intricately regulated by various environmental stimuli. Understanding these interactions is essential for optimizing planting and seedling management but remains challenging due to the trade-off effects of environmental factors on the germination process. We proposed a new conceptual model by viewing seed germination as a dynamic process in a physiological dimension, with the influence of environmental factors and seed heterogeneity characterized by a germination speed and a dispersion coefficient.

The role of expansion and adaptability of face-space for individual differences in face identity processing.

Individuals can strongly vary in their ability to process face identity. Understanding the mechanisms driving these differences is important for theoretical development, and in clinical and applied contexts. Here we investigate the role of face-space properties in relation to individual face identity processing skills.