Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Trends in Screening for Social Risk in US Physician Practices.

Importance: A wealth of research on screening for social risks in health care has emerged, but evidence is lacking on how social risk screening among physician practices has changed over time.

Objectives: To evaluate trends in screening for social risks among US physician practices and examine practice characteristics associated with adoption of social risk screening.

Design, Setting, And Participants: The main analysis used a repeated cross-sectional design to analyze results from US physician practices that completed the National Survey of Healthcare Organizations and Systems, a nationally representative survey of physician practices, in 2017 and 2022.

Bursts of brain erosion: seizures and age-dependent neurological vulnerability.

Hypersynchronous and exaggerated neuronal firing, exemplified by epileptiform activity and seizures, are disruptors of brain function across acute and chronic neuropathological conditions. Here, we focus on how seizure activity, whether as a primary symptom or a secondary comorbid event within a complex pathological setting, adversely impacts neurological trajectories. We discuss experimental and clinical evidence illustrating the participation of neurodegenerative and senescence-like adaptations.

Accountable care organization changes in equity of ambulatory care quality by patient race and ethnicity, 2019-2022.

There is limited information about accountable care organization (ACO) variation in equity of ambulatory care quality. We examine whether equity of care changed for racial and ethnic minority patients from 2019 to 2022 and the extent to which equity of care performance varied for 11 ACOs in Massachusetts over time. We analyzed ACO-level changes in equity of care for 8 ambulatory care quality measures for Asian, Black, and Hispanic patients, measured as the percentage point difference between each group and the majority non-Hispanic White patient group.

Addressing social and health needs in health care: Characterizing case managers' work to address patient-defined goals.

Objective: To test quantitative process measures characterizing the work of social needs case managers as they assisted patients with diverse health-related needs-spanning both medical and social domains.

Study Setting And Design: The study analyzed secondary data on 7076 patients working with 147 case managers from the CommunityConnect social needs case management program in Contra Costa County, California from 2018 to 2021. The service-designed to be holistic with a focus on social determinants as root causes of health issues-helped patients navigate social services, health care, and mental health care.

Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus.

Objective: Status epilepticus (SE) significantly increases the risk for the development of unprovoked seizures, memory loss, and temporal lobe epilepsy. Our prior studies showed that SE increases complement C3 signaling in the hippocampus, which parallels memory deficits. Additionally, C3 knockout (KO) mice were protected against SE-induced memory impairments, suggesting a mechanistic role for C3 in this pathophysiology.

Inhibition Control by Continuous Extractive Fermentation Enhances De Novo 2-Phenylethanol Production by Yeast.

Current microbial cell factory methods for producing chemicals from renewable resources primarily rely on (fed-)batch production systems, leading to the accumulation of the desired product. Industrially relevant chemicals like 2-phenylethanol (2PE), a flavor and fragrance compound, can exhibit toxicity at low concentrations, inhibit the host activity, and negatively impact titer, rate, and yield. Batch liquid-liquid (L-L) In Situ Product Removal (ISPR) was employed to mitigate inhibition effects, but was not found sufficient for industrial-scale application.

Launching Financial Incentives for Physician Groups to Improve Equity of Care by Patient Race and Ethnicity.

Unlabelled: Policy Points What are the facilitators and barriers of physician group participation in a performance-based financial incentive program aimed at improving equity of care by patient race and ethnicity? Launching financial incentives to improve racial equity has required extensive organizational change management for participating physician groups, including major investments to improve quality management systems. Carefully designing financial incentives to encourage equity improvement while managing unintended consequences, and considering physician groups' populations served, baseline maturity of quality management systems, and efforts to assess and address patients' social risk factors have been central to prepare physician groups for financial incentives to improve equity of care. Given the major investments required of physician groups to prepare for financial incentives that reward equity improvement, alignment of equity of care measure specifications and reporting requirements across payers could facilitate physician group engagement.

Nucleophilic Displacement Reactions of Silver-Based Metal-Organic Chalcogenolates.

We report nucleophilic displacement reactions that can increase the dimensionality or coordination number of silver-based metal-organic chalcogenolates (MOChas). MOChas are crystalline ensembles containing one-dimensional (1D) or two-dimensional (2D) inorganic topologies with structures and properties defined by the choice of metal, chalcogen, and ligand. MOChas can be readily prepared from a variety of small-molecule ligands and metals or metal ions.

Intensity of Social Needs Case Management Services and Changes in Hospital and Emergency Department Use Among Adult Medicaid Beneficiaries.

Objectives: We identify the association between high- and low-intensity case management services on hospital and emergency department (ED) use among CommunityConnect patients.

Background: Social needs case management services vary in intensity, including the modality, workforce specialization, and maximum caseload. CommunityConnect is a social needs case management program implemented by Contra Costa Health, a county safety-net health system in California's San Francisco Bay Area.

Laue-DIALS: Open-source software for polychromatic x-ray diffraction data.

Most x-ray sources are inherently polychromatic. Polychromatic ("pink") x-rays provide an efficient way to conduct diffraction experiments as many more photons can be used and large regions of reciprocal space can be probed without sample rotation during exposure-ideal conditions for time-resolved applications. Analysis of such data is complicated, however, causing most x-ray facilities to discard >99% of x-ray photons to obtain monochromatic data.

Consensus on innovations and future directions of community first responder schemes in United Kingdom: a national nominal group technique study.

Aim: We aimed to achieve consensus among NHS and community stakeholders to identify and prioritise innovations in Community First Responder (CFR) schemes.

Methods: We conducted a mixed-methods study, adopting a modified nominal group technique with participants from ambulance services, CFR schemes and community stakeholders. The 1-day consensus workshop consisted of four sessions: introduction of innovations derived from primary research; round-robin discussions to generate new ideas; discussion and ranking of innovations; feedback of ranking, re-ranking and concluding statements.

Sex-Specific Complement and Cytokine Imbalances in Drug-Resistant Epilepsy: Biomarkers of Immune Vulnerability.

Objective: Drug-resistant epilepsy (DRE) poses significant challenges in treatment and management. While seizure-related alterations in peripheral immune players are increasingly recognized, the involvement of the complement system, central to immune function, remains insufficiently explored in DRE. This study aimed to investigate the levels of complement system components and their association with cytokine profiles in patients with DRE.

Rental Housing Deposits and Health Care Use.

Importance: Housing deposits and tenancy supports have become new Medicaid benefits in multiple states; however, evidence on impacts from these specific housing interventions is limited.

Objective: To evaluate the association of rental housing deposits and health care use among Medicaid beneficiaries receiving social needs case management as part of a Whole-Person Care (Medicaid 1115 waiver) pilot program in California.

Design, Setting, And Participants: This cohort study compared changes in health care use among a group of adults who received a housing deposit between October 2018 and December 2021 along with case management vs a matched comparison group who received case management only in Contra Costa County, California, a large county in the San Francisco Bay Area.

Factors Associated with Patient Engagement in a Health and Social Needs Case Management Program.

Introduction: Many patients offered case management services to address their health and social needs choose not to engage. Factors that drive engagement remain unclear. We sought to understand patient characteristics associated with engagement in a social needs case management program and variability by case manager.

Laue-DIALS: open-source software for polychromatic X-ray diffraction data.

Most X-ray sources are inherently polychromatic. Polychromatic ("pink") X-rays provide an efficient way to conduct diffraction experiments as many more photons can be used and large regions of reciprocal space can be probed without sample rotation during exposure-ideal conditions for time-resolved applications. Analysis of such data is complicated, however, causing most X-ray facilities to discard >99% of X-ray photons to obtain monochromatic data.

Community First Responders' role in the current and future rural health and care workforce: a mixed-methods study.

Background: Community First Responders are trained volunteers dispatched by ambulance services to potentially life-threatening emergencies such as cardiac arrest in the first vital minutes to provide care until highly skilled ambulance staff arrive. Community First Responder schemes were first introduced to support ambulance services in rural communities, where access to prehospital emergency care is more likely to be delayed. Evidence is lacking on their contribution to rural healthcare provision, how care is provided and how this might be improved.

3D Nanocrystallography and the Imperfect Molecular Lattice.

Crystallographic analysis relies on the scattering of quanta from arrays of atoms that populate a repeating lattice. While large crystals built of lattices that appear ideal are sought after by crystallographers, imperfections are the norm for molecular crystals. Additionally, advanced X-ray and electron diffraction techniques, used for crystallography, have opened the possibility of interrogating micro- and nanoscale crystals, with edges only millions or even thousands of molecules long.

Outcomes for breast cancer survivors with metastatic disease in a physical activity program for medically underserved cancer survivors.

Purpose: This study examined the effectiveness and feasibility of the Active Living After Cancer (ALAC) program for metastatic breast cancer (MBC) survivors.

Methods: ALAC is a 12-session community-based program to help cancer survivors improve their physical functioning and quality of life through increased physical activity. ALAC participants with MBC (stage IV) were compared to survivors with early-stage breast cancer (stages I and II).