Predicting Increased Incidence of Common Antibiotic-Resistant and Antibiotic-Associated Pathogens Using Ensemble Species Distribution Modeling.

The Centers for Disease Control estimates antibiotic-associated pathogens result in 2.8 million infections and 38,000 deaths annually in the United States. This study applies species distribution modeling to elucidate the impact of environmental determinants of human infectious disease in an era of rapid global change. We modeled methicillin-resistant Staphylococcus aureus and Clostridioides difficile using 31 publicly accessible bioclimatic, healthcare, and sociodemographic variables. Ensemble models were created from 8 unique statistical and machine learning algorithms. Using International Classification of Diseases, 10th Edition codes, we identified 305,528 diagnoses of methicillin-resistant S.aureus and 302,001 diagnoses of C.difficile presence. Three environmental factors - average maximum temperature, specific humidity, and agricultural land density - emerged as major predictors of increased methicillin-resistant S.aureus and C.difficile presence; variables representing healthcare availability were less important. Species distribution modeling may be a powerful tool for identifying areas at increased risk for disease presence and have important implications for disease surveillance systems.

Impact of Medicaid Expansion and Firearm Legislation on Cost of Firearm Injuries.

INTRODUCTION: Firearm injury-related hospitalizations in the U.S. cost $900 million annually. Before the Affordable Care Act, government insurance programs covered 41% of the costs. This study describes the impact of Affordable Care Act Medicaid expansion and state-level firearm legislation on coverage and costs for firearm injuries. METHODS: This cross-sectional study included 35,854,586 hospitalizations from 27 states in 2013 and 2016. Data analyses were performed in 2022. Firearm injuries were classified by mechanism: assault, unintentional, self-harm, or undetermined. The impact of the Affordable Care Act expansion was determined using difference-in-differences analysis. Differences in per capita costs between states with stronger and weak firearm legislation were compared using univariable and multivariable analyses. RESULTS: The authors identified 31,451 initial firearm injury-related hospitalizations. In states with weak firearm legislation, hospitalization costs per 100,000 residents were higher from unintentional ($25,834; p=0.04) and self-inflicted ($11,550; p=0.02) injuries; there were no state-level differences in assault or total per capita firearm-related hospitalization costs. Affordable Care Act expansion increased government coverage of costs by 15 percentage points (95% CI=3, 29) and decreased costs to uninsured/self-pay by 14 percentage points (95% CI=6, 21). In 2016, states with weak firearm legislation and no Affordable Care Act expansion had the highest proportion of hospitalization costs attributed to uninsured/self-pay patients (24%, 95% CI=15, 34). CONCLUSIONS: Affordable Care Act expansion increased government coverage of hospitalizations for firearm injuries. Unintentional and self-harm costs were significantly higher for states with weak firearm legislation. States with weak firearm legislation that did not expand Medicaid had the highest proportion of uninsured/self-pay patients.

Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.

Brain metastases represent an important clinical problem for patients with small-cell lung cancer (SCLC). However, the mechanisms underlying SCLC growth in the brain remain poorly understood. Here, using intracranial injections in mice and assembloids between SCLC aggregates and human cortical organoids in culture, we found that SCLC cells recruit reactive astrocytes to the tumour microenvironment. This crosstalk between SCLC cells and astrocytes drives the induction of gene expression programmes that are similar to those found during early brain development in neurons and astrocytes. Mechanistically, the brain development factor Reelin, secreted by SCLC cells, recruits astrocytes to brain metastases. These astrocytes in turn promote SCLC growth by secreting neuronal pro-survival factors such as SERPINE1. Thus, SCLC brain metastases grow by co-opting mechanisms involved in reciprocal neuron-astrocyte interactions during brain development. Targeting such developmental programmes activated in this cancer ecosystem may help prevent and treat brain metastases.