PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons.

High albedo daytime radiative cooling for enhanced bifacial PV performance.

We present a radiative cooling material capable of enhancing albedo while reducing ground surface temperatures beneath fielded bifacial solar panels. Electrospinning a layer of polyacrylonitrile nanofibers, or nanoPAN, onto a polymer-coated silver mirror yields a total solar reflectance of 99 %, an albedo of 0.96, and a thermal emittance of 0.

Revefenacin Area Under the Curve Spirometry in Patients with Moderate to Very Severe COPD.

Purpose: Several lung function endpoints are utilized in clinical trials of inhaled bronchodilators for chronic obstructive pulmonary disease (COPD). Trough forced expiratory volume in 1 second (FEV) is a commonly reported endpoint in COPD trials and can be complemented by area under the FEV vs time curve (FEV AUC), which provides information on duration and consistency of bronchodilation over a dosing interval. Revefenacin, a once-daily bronchodilator, significantly improved lung function in patients with COPD when measured by trough FEV in two replicate Phase 3 trials.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses.

The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication of a broad range of viruses that rely on ER protein quality control. We found, by screening a panel of deoxynojirimycin and cyclitol glycomimetics, that the mechanism-based ER α-glucosidase II inhibitor, 1,6--cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 replication in lung epithelial cells, halting intracellular generation of mature spike protein, reducing production of infectious progeny, and leading to reduced syncytium formation. Through activity-based protein profiling, we confirmed ER α-glucosidase II inhibition in primary airway epithelial cells, grown at the air-liquid interface.

The Landscape of Genomic Services for Inherited Retinal Degenerations (IRDs) Across Europe.

Purpose: To map the existing genomic services available for patients with IRDs across Europe.

Methods: A survey was conducted to 24 ophthalmic and/or genetic specialists across 19 European countries. The survey was conducted in an interview style via zoom for participants from 17 out of 19 countries.

Exploring the Experience of Community Participation Among Individuals With Serious Mental Illness.

People with serious mental illness (SMI) encounter restrictions in the quantity of their community participation. Less is known about the quality of their participation. We aimed to explore the relationship between symptoms of SMI and the daily experience (i.

Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021.

Intrauterine insemination timing models-LH can only take you so far.

Research Question: Can an optimal LH threshold algorithm accurately predict timing of ovulation for natural cycle-intrauterine insemination (NC-IUI)?

Design: A retrospective cohort study (2018-2022) including 2467 natural cycles. Ovulation timing for these cycles was determined using a previously developed AI model. Two LH thresholds, low and high, were determined in the LH algorithm.

Two decades of clear-cutting threats in the Brazilian Amazonian protected areas around the Jirau, Santo Antônio, and Belo Monte large dams.

Deforestation rates in the Amazon have markedly increased in the last few years, affecting non-protected and protected areas (PAs). Brazil is a hotspot of Protected Area Downgrading, Downsizing, and Degazettement (PADDD) events, with most events associated with infrastructure projects. Despite the threats dams impose on PAs, there is a knowledge gap in assessing deforestation in PAs around large dams in the Amazon.

Conformational and Electronic Variations in 1,2- and 1,5a-Cyclophellitols and their Impact on Retaining α-Glucosidase Inhibition.

Glycoside hydrolases (glycosidases) take part in myriad biological processes and are important therapeutic targets. Competitive and mechanism-based inhibitors are useful tools to dissect their biological role and comprise a good starting point for drug discovery. The natural product, cyclophellitol, a mechanism-based, covalent and irreversible retaining β-glucosidase inhibitor has inspired the design of diverse α- and β-glycosidase inhibitor and activity-based probe scaffolds.

Clinical Burden of Chronic Obstructive Pulmonary Disease in Patients with Suboptimal Peak Inspiratory Flow.

Introduction: Many patients with chronic obstructive pulmonary disease (COPD) may derive inadequate benefit from dry powder inhalers (DPIs) because of suboptimal peak inspiratory flow (sPIF).

Objectives: To assess the clinical burden of COPD by characterizing the clinical characteristics of participants with sPIF against medium-low resistance DPIs versus those with optimal PIF (oPIF) from two phase 3 clinical trials.

Methods: Baseline data were collected from two randomized, controlled, phase 3 trials (NCT03095456; NCT02518139) in participants with moderate-to-severe COPD.

Evidence for shallow cognitive maps in schizophrenia.

Individuals with schizophrenia can have marked deficits in goal-directed decision making. Prominent theories differ in whether schizophrenia (SZ) affects the ability to exert cognitive control, or the motivation to exert control. An alternative explanation is that schizophrenia negatively impacts the formation of cognitive maps, the internal representations of the way the world is structured, necessary for the formation of effective action plans.

Loneliness in the Daily Lives of People With Mood and Psychotic Disorders.

Background And Hypothesis: Loneliness, the subjective experience of feeling alone, is associated with physical and psychological impairments. While there is an extensive literature linking loneliness to psychopathology, limited work has examined loneliness in daily life in those with serious mental illness. We hypothesized that trait and momentary loneliness would be transdiagnostic and relate to symptoms and measures of daily functioning.

Poverty-Food Insecurity Nexus in the Post-Construction Context of a Large Hydropower Dam in the Brazilian Amazon.

Within the 2030 Sustainable Development Agenda, large hydropower dams are positioned as a sustainable energy source, notwithstanding their adverse impacts on societies and ecosystems. This study contributed to ongoing discussions about the persistence of critical social issues, even after the investments of large amounts of resources in areas impacted by the construction of large hydropower dams. Our study focused on food insecurity and evaluated this issue in the city of Altamira in the Brazilian Amazon, which has been profoundly socially and economically impacted by the construction, between 2011 and 2015, of Brazil's second-largest dam, namely, Belo Monte.

Basis for the diversity and extent in loss of digestible nutrients created by dietary phytin: Emphasis on fowl and swine.

Phytin is the Ca-Mg-K salt of phytic acid that is created and deposited in the aleurone layer and/or germ of grains and legumes. Its high presence in feedstuffs for fowl and swine diets results in it being a universal and significant impediment to optimum performance. Phytin impairs gastrointestinal recovery of a wide array of nutrients, the effect varying with the nutrient concerned.

Administration's Share of Personnel in Veterans Health Administration and Private Sector Care.

Importance: Health care administrative overhead is greater in the US than some other nations but has not been assessed in the Veterans Health Administration (VHA).

Objective: To compare administrative staffing patterns in the VHA and private (non-VHA) sectors.

Design, Setting, And Participants: This cross-sectional study was conducted using US employment data from 2019, prior to pandemic-related disruptions in health care staffing, and was carried out between January 14 and August 10, 2023.

Linking Toxicology and Human Health Through the Exposome.

Current analytical technology and continuing maturation of -omics methodology have enabled detailed assessment of human exposure via the exposome. Topics exploring the connection between etiology of disease and toxicology were presented at the 2023 Fall American Chemical Society meeting.