Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

Hemodynamic cortical ripples through cyclicity analysis.

A fine-grained understanding of dynamics in cortical networks is crucial to unpacking brain function. Resting-state functional magnetic resonance imaging (fMRI) gives rise to time series recordings of the activity of different brain regions, which are aperiodic and lack a base frequency. Cyclicity analysis, a novel technique robust under time reparametrizations, is effective in recovering the temporal ordering of such time series, collectively considered components of a multidimensional trajectory.

Activity measurements and calibrations for Ac in radioactive equilibrium with its progeny.

The massic activity of Ac in 0.1 mol/L HCl was measured by multiple primary methods over four consistent measurement campaigns. Results from the triple-to-double coincidence ratio (TDCR) method of liquid scintillation (LS) counting were in accord with other LS-based primary methods.

The Influence of X Chromosome Parent-of-Origin on Glycemia in Individuals with Turner Syndrome.

Introduction: The cause of increased diabetes mellitus (DM) risk in individuals with Turner syndrome (TS) is poorly understood. Parent-of-origin effects related to whether the maternal or paternal X chromosome (Xchr) remains intact have been found for several TS phenotypes, including hypercholesterolemia. Therefore, Xchr parent-of-origin may impact DM risk in TS.

Neurovascular mechanisms of cognitive aging: Sex-related differences in the average progression of arteriosclerosis, white matter atrophy, and cognitive decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity.

A major functional role of synovial fluid is to reduce the rate of cartilage fatigue failure under cyclical compressive loading.

Objective: Based on our recent study, which showed that cartilage fatigue failure in reciprocating sliding contact results from cyclical compressive forces, not from cyclical frictional forces, we hypothesize that a major functional role for synovial fluid (SF) is to reduce the rate of articular cartilage fatigue failure from cyclical compressive loading.

Design: The rate of cartilage fatigue failure due to repetitive compressive loading was measured by sliding a glass lens against an immature bovine cartilage tibial plateau strip immersed in mature bovine SF, phosphate-buffered saline (PBS), or SF/PBS dilutions (50% SF and 25% SF; n = 8 for all four bath conditions). After 24 h of reciprocating sliding (5400 cycles), samples were visually assessed, and if damage was observed, the test was terminated; otherwise, testing was continued for 72 h (16,200 cycles), with solution refreshed daily.

Correlating Predicted Adjuvant Therapy Benefit and Risk of Recurrence Between Breast Cancer Index (BCI) and the 21-Gene Oncotype DX Recurrence Score (RS).

Introduction: Breast Cancer Index (BCI) is a genomic assay that evaluates the benefit of extending endocrine therapy (ET) from 5 to 10 years and predicts recurrence risk (RR). We evaluated the association between BCI and Oncotype DX (ODX).

Patients: Women with hormone receptor (HR)-positive early-stage breast cancer (EBC) who had BCI and ODX performed were included.

Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes.

Unlabelled: Circulating tumor cells (CTCs) captured from the bloodstream of patients with solid tumors have the potential to accelerate precision oncology by providing insight into tumor biology, disease progression and response to treatment. However, their potential is hampered by the lack of standardized CTC enrichment platforms across tumor types. EpCAM-based CTC enrichment, the most commonly used platform, is limited by EpCAM downregulation during metastasis and the low EpCAM expression in certain tumor types, including the highly prevalent and lethal NSCLC.

Living Well: Protocol for a web-based program to improve quality of life in rural and urban ovarian cancer survivors.

Background: Ovarian cancer (OC) survivors commonly experience chronic symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms, poor health-related quality of life (HRQOL), and a generally poor prognosis. Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival. Accessible psychosocial interventions to improve HRQOL and clinical outcomes are needed.

Widefield imaging system with two fluorescence and two reflectance channels, a single sCMOS detector, and shielded illumination.

Significance: Widefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with spectrally compatible fluorescent indicators as well as hemodynamics via oxy- and deoxyhemoglobin absorption. Versatile and cost-effective imaging systems are needed for large-scale, color-multiplexed imaging of multiple fluorescent and intrinsic contrasts.

Aim: We aim to develop a system for mesoscopic imaging of two fluorescent and two reflectance channels.

Family Medicine Clinician Screening and Barriers to Communication on Food Insecurity: A CERA General Membership Survey.

Purpose: Food insecurity (FI) is a hidden epidemic associated with worsening health outcomes affecting 33.8 million people in the US in 2021. Although studies demonstrate the importance of health care clinician assessment of a patient's food insecurity, little is known about whether Family Medicine clinicians (FMC) discuss FI with patients and what barriers influence their ability to communicate about FI.

Neurovascular Mechanisms of Cognitive Aging: Sex-Related Differences in the Average Progression of Arteriosclerosis, White Matter Atrophy, and Cognitive Decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data ( = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity.

A new evaluation of the decay data for Ho.

The β-emitter Ho is of interest as a potential radiolabel for therapeutic medical applications. A new decay data evaluation for Ho has been performed using the Decay Data Evaluation Project (DDEP) methodology. New recommended values for the half-life, γ-ray emission probabilities, β branching ratios, and other relevant nuclear and atomic data are provided.

Next-Generation HER2-Targeted Antibody-Drug Conjugates in Breast Cancer.

Human epidermal growth factor receptor 2 (HER2) tyrosine kinase is overexpressed in 20% of breast cancers and associated with a less favorable prognosis compared to HER2-negative disease. Patients have traditionally been treated with a combination of chemotherapy and HER2-targeted monoclonal antibodies such as trastuzumab and pertuzumab. The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) represent a novel class of therapeutics in breast cancer.

Absolute emission intensities of the gamma rays from the decay of Ra and Pb progenies and the half-life of the Pb decay.

Absolute gamma-ray emission intensities for 36 characteristic gamma rays from the decay of Ra, Pb, and their progeny were determined by measuring sources calibrated for activity by means of primary methods based on well-defined high-purity germanium (HPGe) detectors at both NIST and NPL. Results from the two laboratories agree with recent data evaluations, except for gamma rays with low emission intensities. The decay schemes have been re-balanced based on the new results.

Analgesic onset and efficacy of a fast-acting formulation of acetaminophen in a postoperative dental impaction pain model.

Objectives: Speed of onset can be critical to an analgesic's efficacy treating acute pain. To enhance onset, a new oral acetaminophen formulation intended to be fast acting was developed. Two studies evaluated the analgesic onset, efficacy, and safety of this fast-acting acetaminophen (FA-acetaminophen) tablet relative to commercial acetaminophen caplets (ES-acetaminophen) and commercial ibuprofen liquid-filled gelatin capsules (LG-ibuprofen).

Liquid scintillation efficiencies, gamma-ray emission intensities, and half-life for Gd-153.

Gadolinium-153 was standardized for activity by live-timed anticoincidence counting and an ampoule was submitted to the international reference system (SIR). Absolute emission intensities for the main γ rays were determined with calibrated high-purity germanium (HPGe) and lithium-drifted silicon (Si(Li)) detectors. A revised decay scheme is indicated, with no probability of direct electron capture to the Eu ground state.

Study Design and Protocol of the Multisite Pregnancy 24/7 Cohort Study.

Hypertensive disorders of pregnancy and other adverse pregnancy outcomes (APOs) are associated with an increased risk of future maternal cardiovascular disease. Physical activity during pregnancy reduces the risk of these APOs, yet few meet physical activity guidelines during pregnancy. Little is known about the role of sedentary behavior or sleep in APOs, a critical gap in knowledge given these behaviors comprise the majority of a 24-hour day.

Comparison of calibration coefficients for a vinten ionization chamber simulated using four Monte Carlo methods.

The Vinten 671 ionization chamber (VIC) was modelled using Monte Carlo (MC) programs EGSnrc, Penelope, and TOPAS. Several national measurement institutes have VICs with well-characterized response relationships and have measured calibration coefficients for many radionuclides. Twelve radionuclides with various decay emissions were assessed as well as 14 monoenergetic photon sources and 10 monoenergetic electron sources.