UCSF

ABSTRACTRecent academic and activist critiques raise important points about the ways in which coloniality, migration and racialization are often overlooked in global health research and practice. In particular, these critiques highlight how such structural forces perpetuate inequalities and exclusions, as well as processes of epistemic violence in global health. While agreeing with these critical interventions, this paper argues for a focus on care and the importance that concrete acts and systems of care in postcolonial, migratory and racialized contexts have on the suffering and vulnerability of individuals and communities. Drawing on case studies from multiple different geographic and social contexts, we argue that the perspective of racialization can highlight how multi-layered inequalities in global healthcare are shaped by the intertwined processes of coloniality and migration; thereby explaining the contextual, structural vulnerability of specific groups of people to certain health conditions and their exclusion from adequate healthcare resources. We argue that social scientists and critical global health scholars and practitioners can play a central role in bringing the three strands of research - coloniality, migration and racialization - into conversation to explore their potential for jointly advancing the care and well-being of individuals and communities in different geographical and social contexts.

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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.

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.

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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The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study ( https://osf.io/gsru7 ), we analysed intracranial electroencephalography recordings from widespread brain regions in a large developmental cohort. Using task-based (that is, attention to to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93-54.00 years, 63 males; n electrodes = 5,691), we mapped aperiodic (1/ƒ-like) activity, a proxy of neural noise, where steeper slopes indicate less noise and flatter slopes indicate more noise. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In the prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in grey matter volume are similarly associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC control during adolescence in the development of attention and memory.

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Collagen embodies an intriguing paradox in protein biology. Despite being one of the most abundant protein superfamilies in vertebrates and having a seemingly simple structural organization, its biosynthesis is anything but straightforward. This apparent simplicity masks a complex and often contradictory biosynthetic landscape that poses significant challenges, particularly for newcomers to the field. Rather than following a linear or uniform pathway, collagen biosynthesis involves a coordinated series of tightly regulated steps, cotranslational post-translational modifications (PTMs), chain selection and registration, triple helix formation, and secretion, orchestrated by a specialized machinery, collectively termed the collagen molecular ensemble. This ensemble must overcome unconventional paradigms in protein biogenesis, rife with exceptions and unresolved questions. In this perspective, I examine underexplored aspects of the collagen biosynthetic machinery, spotlighting challenges in decoding the regulatory logic of PTMs, the spatial dynamics of trimer assembly, the functional consequences of chain registration, and the type-specific routes of secretion. By charting these uncertainties, I aim to challenge prevailing assumptions and invite interdisciplinary insight to help unravel the remaining mysteries of collagen biosynthesis.