Contributing factors to the oxidation-induced mutational landscape in human cells.

8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers.

Case report of central serous chorioretinopathy with intraretinal fluid and normal fundus fluorescein and indocyanine green angiography.

A 73-year-old man was diagnosed with central serous chorioretinopathy (CSCR). He had atypical features including a normal indocyanine green angiography (ICG) and fundus fluorescein angiography (FFA), uncommon age group for initial diagnosis and a finding of intraretinal fluid. This case report is the first of our knowledge that exemplifies this type of unusual clinical presentation for CSCR.

STARD7 maintains intestinal epithelial mitochondria architecture, barrier integrity, and protection from colitis.

Susceptibility to inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) is linked with loss of intestinal epithelial barrier integrity and mitochondria dysfunction. Steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain-containing protein 7 (STARD7) is a phosphatidylcholine-specific (PC-specific) lipid transfer protein that transports PC from the ER to the mitochondria, facilitating mitochondria membrane stabilization and respiration function. The aim of this study was to define the contribution of STARD7 in the regulation of the intestinal epithelial mitochondrial function and susceptibility to colitis.

Structural basis of gap-filling DNA synthesis in the nucleosome by DNA Polymerase β.

Single-strand breaks (SSBs) are one of the most prevalent forms of DNA damage found in the chromatinized genome and are repaired by direct single-strand break repair (SSBR) or base excision repair (BER). DNA polymerase beta (Pol β) is the primary enzyme responsible for processing the 1-nt gap intermediate in chromatin during SSBR and BER. However, the mechanism used by Pol β to process a 1-nt gap in the context of the nucleosome and chromatin remains poorly understood.

Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.

Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be replaced by Blm10 to form Blm10:CP, which promotes ATP-independent degradation of disordered proteins. Here, we present evidence of distinct parallel assembly pathways for CP by solving five cryo-EM structures including a Blm10:13S pre-assembly intermediate.

Improving GWAS performance in underrepresented groups by appropriate modeling of genetics, environment, and sociocultural factors.

Genome-wide association studies (GWAS) and polygenic score (PGS) development are typically constrained by the data available in biobank repositories in which European cohorts are vastly overrepresented. Here, we increase the utility of non-European participant data within the UK Biobank (UKB) by characterizing the genetic affinities of UKB participants who self-identify as Bangladeshi, Indian, Pakistani, "White and Asian" (WA), and "Any Other Asian" (AOA), towards creating a more robust South Asian sample size for future genetic analyses. We assess the relationships between genetic structure and self-selected ethnic identities resulting in consistent patterns of clustering used to train a support vector machine (SVM).

Cannabinoids and General Anesthetics: Revisiting Molecular Mechanisms of Their Pharmacological Interactions.

Cannabis has been used for recreation and medical purposes for more than a millennium across the world; however, its use's consequences remain poorly understood. Although a growing number of surgical patients are regular cannabis consumers, little is known regarding the pharmacological interactions between cannabis and general anesthetics; consequently, there is not a solid consensus among anesthesiologists on the perioperative management of these patients. The existing evidence about the molecular mechanisms underlying pharmacological interactions between cannabinoids and anesthetic agents, both in animal models and in humans, shows divergent results.

Factors Affecting Daily Functioning in Turkish Patients with Obstructive Sleep Apnea.

This study aims to examine the factors affecting the daily functioning of patients with obstructive sleep apnea (OSA). In addition to the polysomnography records of 361 patients, participants completed the Turkish FOSQ-10 (Functional Outcomes of Sleep-10), Medical Outcome Survey Short Form-12, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). First, the psychometrics properties of the Turkish FOSQ-10 were evaluated.

Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine.

Base excision repair is the main pathway involved in active DNA demethylation. 5-formylcytosine and 5-carboxylcytosine, two oxidized moieties of methylated cytosine, are recognized and removed by thymine DNA glycosylase (TDG) to generate an abasic site. Using single molecule fluorescence experiments, we study TDG in the presence and absence of 5-formylcytosine.

Development and implementation of a Community Pharmacy "Bootcamp" activity - A pilot study.

Objective: The objectives of this study are to describe 1) the implementation of and 2) student performance and perceptions during an innovative classroom activity.

Methods: The Bootcamp was designed as an exercise in productive failure for second-year PharmD students enrolled in a community pharmacy elective course. A prescription verification exercise was introduced; however, students were intermittently interrupted with common community pharmacist tasks.

Brief Educational Workshops in Secondary Schools Trial (BESST): a cluster randomised controlled trial. Secondary analysis in those with elevated symptoms of depression.

Background: Depression and anxiety are increasingly prevalent in adolescents. The Brief Educational Workshops in Secondary Schools Trial investigated the effectiveness of a brief self-referral stress workshop programme for sixth-form students aged 16-18 years old.

Objective: This study conducted a secondary analysis on the outcomes of participants with elevated depressive symptoms at baseline.

Becoming an Open Dialogue practitioner: a qualitative study of practitioners' training experiences and transitioning to practice.

Introduction: In the context of transforming mental healthcare towards more personalised and recovery-oriented models, Open Dialogue has attracted significant international interest. Open Dialogue proposes a way of organising services and delivering care that supports an immediate response to crisis, relational continuity of care, a social network approach and the empowerment of networks through shared decision-making and a flattened hierarchy. The ODDESSI trial currently being conducted in the UK is assessing the model's clinical and cost-effectiveness.

Psychometric Properties of the Turkish Version of Self-Efficacy Measure for Sleep Apnea (SEMSA) Instrument.

Background: Determining the self-efficacy perceptions of obstructive sleep apnea (OSA) patients has a key role in health care practices. With further evaluation, the Self-Efficacy Measure for Sleep Apnea (SEMSA) could serve as a useful scale to develop specific interventions to increase self-efficacy in patients with OSA during the acceptance and maintenance of continuous positive airway pressure (CPAP) therapy.

Objective: The aim of this study is to translate the SEMSA into Turkish and to evaluate the psychometric properties of the translation.

Nucleolytic processing of abasic sites underlies PARP inhibitor hypersensitivity in ALC1-deficient BRCA mutant cancer cells.

Clinical success with poly (ADP-ribose) polymerase inhibitors (PARPi) is impeded by inevitable resistance and associated cytotoxicity. Depletion of Amplified in Liver Cancer 1 (ALC1), a chromatin-remodeling enzyme, can overcome these limitations by hypersensitizing BReast CAncer genes 1/2 (BRCA1/2) mutant cells to PARPi. Here, we demonstrate that PARPi hypersensitivity upon ALC1 loss is reliant on its role in promoting the repair of chromatin buried abasic sites.

Psychometric evaluation of the Brazilian-Portuguese version of the Functional Outcome of Sleep Questionnaire 10 (FOSQ-10) in patients with obstructive apnea.

Objective: Perform the validation and psychometric evaluation of the Brazilian-Portuguese translation of the Functional Outcome of Sleep Questionnaire 10 (FOSQ10).

Materials And Methods: 182 patients (65 females 48.3±14.

Potential perioperative cardiovascular outcomes in cannabis/cannabinoid users. A call for caution.

Background: Cannabis is one of the most widely used psychoactive substances. Its components act through several pathways, producing a myriad of side effects, of which cardiovascular events are the most life-threatening. However, only a limited number of studies address cannabis's perioperative impact on patients during noncardiac surgery.

Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT.

Identifying cell types and states remains a time-consuming, error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data.