Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries.

Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2.

Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration.

We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) ( = 5,579) and UK Biobank studies ( = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years.

Tumor cell-derived spermidine promotes a protumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly affect the immune system, but the mechanisms driving these interactions are not completely clear. Here, we demonstrate that the polyamine metabolite spermidine (SPD) was elevated in the GBM tumor microenvironment.

Intestinal stem cells enhance local mucosal immunity through apoptotic body phagocytosis.

Modulation of immune tone at mucosal surfaces is critical to maintain homeostasis while facilitating the handling of emerging threats. One dynamic component of immune modulation is the phagocytosis and clearance of apoptotic bodies known as efferocytosis that inhibits inflammation by promoting its resolution. Here, we evaluated the effects of apoptotic body phagocytosis by intestinal epithelial stem and progenitor cells (ISCs).

Cost-Associated Unmet Dental, Vision, And Hearing Needs Among Low-Income Medicare Advantage Beneficiaries.

Medicare Advantage (MA) supplemental benefits offered at no or low premiums are a key value proposition for low-income beneficiaries. Despite nearly $20 billion in rebate payments to MA plans for funding supplemental benefits, their quality or enrollee access is not monitored. Using 2018-19 Medicare Current Beneficiary Survey data linked to MA plan data, we found that regardless of plan benefit generosity, low-income beneficiaries were more likely to report dental, vision, and hearing unmet needs because of cost.

Assessing the Deterrent Effects of Ignition Interlock Devices.

Introduction: Ignition interlock devices installed after conviction for driving under the influence of alcohol (DUI) have been shown to reduce subsequent DUI arrests (specific deterrence). However, there is little evidence on how interlock-device penalties might affect general deterrence, that is, deterring people from driving after consuming alcohol prior to a DUI conviction.

Methods: A discrete choice experiment was conducted and data were analyzed in 2023 with 583 U.

Geographic Variation in Cesarean Sections in the United States: Trends, Correlates, and Other Interesting Facts.

Analyzing data spanning three decades covering the near universe of births, we study county-level differences in Cesarean section (C-section) rates among first-time mothers of singleton births. Our research reveals persistent geographic variation in C-section rates for both low- and high-risk groups. Counties with elevated C-section rates consistently perform more C-sections across mothers at all levels of appropriateness for the procedure.

Does Practice Match Protocol? A Comparison of Triage-to-Provider Time Among More vs. Less Acute Emergency Department Patients.

Introduction The Emergency Severity Index (ESI) stratifies emergency department (ED) patients for triage, from "most acute" (level 1) to "least acute" (level 5). Many EDs have a split flow model where less acute (ESI 4 and 5) are seen in a fast track, while more acute (ESI 1, 2, and 3) are seen in the acute care area. A core principle of emergency medicine (EM) is to attend to more acute patients first.

The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton.

The exon junction complex (EJC), nucleated by EIF4A3, is indispensable for mRNA fate and function throughout eukaryotes. We discover that EIF4A3 directly controls microtubules, independent of RNA, which is critical for neural wiring. While neuronal survival in the developing mouse cerebral cortex depends upon an intact EJC, axonal tract development requires only Eif4a3.

Exploring patient and system factors impacting undertriage of injured patients meeting national field triage guideline criteria.

Background: Trauma systems save lives by coordinating timely and effective responses to injury. However, trauma system effectiveness varies geographically, with worse outcomes observed in rural settings. Prior data suggest that undertriage may play a role in this disparity.

Medicare Advantage Plan Star Ratings and County Social Vulnerability.

Importance: The star rating of a Medicare Advantage (MA) plan is meant to represent plan performance, and it determines the size of quality bonuses. Consumer access to MA plans with a high star rating may vary by the extent of social vulnerability in geographic regions.

Objective: To examine the association between a county's Social Vulnerability Index (SVI) and the star rating of a county's MA plans.

Association between timing of operative interventions and mortality in emergency general surgery.

Background: Emergency general surgery (EGS) often demands timely interventions, yet data for triage and timing are limited. This study explores the relationship between hospital arrival-to-operation time and mortality in EGS patients.

Study Design: We performed a retrospective cohort study using an EGS registry at four hospitals, enrolling adults who underwent operative intervention for a primary American Association for the Surgery of Trauma-defined EGS diagnosis between 2021 and 2023.

Bubble reachers and uncivil discourse in polarized online public sphere.

Early optimism saw possibilities for social media to renew democratic discourse, marked by hopes for individuals from diverse backgrounds to find opportunities to learn from and interact with others different from themselves. This optimism quickly waned as social media seemed to breed ideological homophily marked by "filter bubbles" or "echo chambers." A typical response to the sense of fragmentation has been to encourage exposure to more cross-partisan sources of information.

The TREE Program: Promoting Positive Early Childhood Experiences During Well-Child Visits.

This feasibility study evaluated the developmental coaching TREE (Talk Read Engage Encourage) program for historically marginalized children ages 0 to 2 years, embedded within pediatric visits, examining if TREE could enhance caregiver-child interactions and increase pediatric resident report of competency and self-efficacy in coaching caregivers. Using a quasi-experimental design, a convenience sample (n = 167 families) was recruited (79 intervention; 88 control). Follow-up data were obtained from 45% of families (38 intervention; 38 control), impacted by COVID-19 attendance.

Examining the relationship between social determinants of health, measures of structural racism and county-level overdose deaths from 2017-2020.

Introduction: Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020.

Methods: This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure.

A human-specific enhancer fine-tunes radial glia potency and corticogenesis.

Humans evolved an extraordinarily expanded and complex cerebral cortex, associated with developmental and gene regulatory modifications . Human accelerated regions (HARs) are highly conserved genomic sequences with human-specific nucleotide substitutions. Although there are thousands of annotated HARs, their functional contribution to human-specific cortical development is largely unknown .

The Impact of Medicaid Accountable Care Organizations on Health Care Utilization, Quality Measures, Health Outcomes and Costs from 2012 to 2023: A Scoping Review.

Most of the evidence regarding the success of ACOs is from the Medicare program. This review evaluates the impacts of ACOs within the Medicaid population. We identified 32 relevant studies published between 2012 and 2023 which analyzed the association of Medicaid ACOs and health care utilization ( = 21), quality measures ( = 18), health outcomes ( = 10), and cost reduction ( = 3).

Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity.

Cancer stem cell hypothesis 2.0 in glioblastoma: Where are we now and where are we going?

Over the past 2 decades, the cancer stem cell (CSC) hypothesis has provided insight into many malignant tumors, including glioblastoma (GBM). Cancer stem cells have been identified in patient-derived tumors and in some mouse models, allowing for a deeper understanding of cellular and molecular mechanisms underlying GBM growth and therapeutic resistance. The CSC hypothesis has been the cornerstone of cellular heterogeneity, providing a conceptual and technical framework to explain this longstanding phenotype in GBM.

One year later: What role did trust in public officials and the medical profession play in decisions to get a booster and to overcome vaccine hesitancy?

Physicians may have an important role to play in promoting boosters as well as reducing COVID-19 vaccine hesitancy, but the relationship between hesitancy and trust in the medical profession and these behaviors has been underexplored. A representative online panel of 1,967 US adults that included oversamples of minoritized and rural populations were surveyed in April 2021 and June 2022 regarding their booster and vaccine status and intentions, their views of the medical profession, and their levels of trust in their own doctors, and national and state/local officials. Eighty percent of those vaccinated in 2021 had received a booster by 2022, while fewer than half of those initially reluctant to get a vaccine had gotten one by Wave 2 of the survey.

Should I stay or should I go? Transsulfuration influences invasion and growth in glioblastoma.

A major challenge in treating patients with glioblastoma is the inability to eliminate highly invasive cells with chemotherapy, radiation, or surgical resection. As cancer cells face the issue of replicating or invading neighboring tissue, they rewire their metabolism in a concerted effort to support necessary cellular processes and account for altered nutrient abundance. In this issue of the JCI, Garcia et al.