UCSF

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INTRODUCTION: Latinx individuals are disproportionately affected by alcohol use disorder (AUD). Understanding Latinx individuals barriers and facilitators to reach AUD-related goals can help implement culturally and linguistically concordant interventions to improve alcohol-related outcomes. METHODS: We conducted semi-structured qualitative interviews with Latinx, Spanish-speaking men with AUD within 20 weeks of hospital discharge who were seen by an addiction consult team during hospitalization in an urban, safety-net hospital in San Francisco. Interviews focused on the facilitators and barriers to participants AUD-related goals pre-, during, and post-hospitalization. We recorded and transcribed interviews and used a mixed deductive and inductive analytic approach until we reached thematic saturation (n = 10). RESULTS: We identified three major themes: 1. Hospitalization was an actionable moment for change; 2. Social factors were closely intertwined with AUD goals; and 3. Accessible addiction, physical health, and mental health services can help achieve AUD goals. CONCLUSIONS: Hospitalization may serve as a facilitator for Latinx individuals with AUD to achieve AUD goals. Addressing social determinants of health including housing, immigration status, and social support networks before, during, and after hospitalization, may help facilitate AUD goals. Providing language-concordant and accessible services may decrease barriers to achieving AUD goals.

Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how the TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism, while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as benchmarks for drug-induced immune activation in ex vivo models of the TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of the TIME underscores the significance of human patient-derived models in elucidating the complexities of anti-tumor immunity and therapeutic interventions.

Fetal growth restriction (FGR) is associated with perinatal death and adverse birth outcomes, as well as long-term complications, including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. Placental epigenetic reprogramming associated with FGR may mediate these long-term outcomes. Placental malaria (PM), characterized by sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous space, is the leading global cause of FGR, but its impact on placental epigenetics is unknown. We hypothesized that placental methylomic profiling would reveal common and distinct mechanistic pathways of non-malarial and PM-associated FGR. We analyzed placentas from a US cohort with no malaria exposure (n = 12) and a cohort from eastern Uganda, a region with a high prevalence of malaria (n = 12). From each site, 8 cases of FGR and 4 healthy controls were analyzed. PM was diagnosed by placental histopathology. We compared the methylation levels of over 850K CpGs of the placentas using Infinium MethylationEPIC v1 microarray. Non-malarial FGR was associated with 65 differentially methylated CpGs (DMCs), whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls without FGR. One DMC (cg16389901, located in the promoter region of BMP4) was commonly hypomethylated in both groups. We identified 522 DMCs between non-malarial FGR vs. PM-FGR placentas, independent of differing geographic location or cellular composition. Placentas with PM-associated FGR have distinct methylation profiles compared to placentas with non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. Larger cohort studies are needed to determine the distinct long-term health outcomes in PM-associated FGR pregnancies.

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Healthcare-associated infections (HAI), particularly those involving multi-drug resistant organisms (MDRO), pose a significant public health threat. Understanding the transmission of these pathogens in short-term acute care hospitals (STACH) is crucial for effective control. Mathematical and computational models play a key role in studying transmission but often overlook the influence of long-term care facilities (LTCFs) and the broader community on transmission. In a systematic scoping review of 4,733 unique studies from 2016 to 2022, we explored the modeling landscape of the hospital-community interface in HAI-causing pathogen transmission. Among the 29 eligible studies, 28 % (n = 8) exclusively modeled LTCFs, 45 % (n = 13) focused on non-healthcare-related community settings, and 31 % (n = 9) considered both settings. Studies emphasizing screening and contact precautions were more likely to include LTCFs but tended to neglect the wider community. This review emphasizes the crucial need for comprehensive modeling that incorporates the communitys impact on both clinical and public health outcomes.

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PURPOSE: In this work, we adopt the MR fingerprinting (MRF) framework and leverage its flexibility in quantitative pulse sequence design to propose improved balanced steady-state free precession (bSSFP)-based hyperpolarized Carbon-13 (13C) acquisitions for robust metabolic conversion rate quantification. METHODS: Spectrally selective bSSFP-based acquisitions with variable RF excitation were implemented for [1-13C]pyruvate and used in conjunction with prior implementation of [1-13C]lactate selective bSSFP imaging. MRF framework parameter estimation was performed using dictionary-based template matching. Influences of bSSFP-based acquisitions and sigmoid RF excitation scheme were assessed with simulation experiments and Monte Carlo evaluation. Methods were then compared using experimental data from rat kidney acquired on a clinical 3 T scanner. RESULTS: Simulations indicated that combining bSSFP-based acquisitions and variable RF excitation (MRF-Sigmoid) exhibited bias <0.1% across the majority (86%) of combinations of pyruvate-to-lactate conversion rate (kPL) and noise level investigated when estimating kPL with the MRF framework. bSSFP-based experiments, with and without sigmoid excitation scheme, showed lower variance in fits at all levels of kPL and noise investigated compared to the method used in prior work by this group (hybrid gradient echo). Positive, linear correlations were found for in vivo voxel-wise estimates of kPL in healthy rat kidneys when comparing all experiment methods. MRF-Sigmoid experiment design increased pyruvate cumulative SNR by 3.5-fold over hybrid gradient echo while maintaining similar lactate cumulative SNR. CONCLUSION: The use of the MRF framework for kPL estimation demonstrates the feasibility of dictionary-based template matching and can be used to accurately estimate physiologically relevant kPL and improve cumulative SNR.