Faculty Bibliography

OBJECTIVE/UNASSIGNED:This mixed methods study explores gender differences in, and reasons for, toothbrushing and flossing among Mexican-origin adults. METHODS/UNASSIGNED:Interviews and surveys about oral hygiene behaviors were collected from 72 adults (ages 21-40) living on the California-Mexico border. Interviews were audio-recorded, transcribed in their original language (English/Spanish), then coded. Survey responses were linked to coded transcripts in Dedoose. Qualitative reports were thematically analyzed for each behavior, stratified into four groups by gender and whether or not participants met American Dental Association (ADA) weekly guidelines (brushing ≥ 14/week; flossing ≥ 7/week). Self-reported weekly frequencies of brushing and flossing were collected continuously, and then dichotomized as meeting guidelines or not. Kruskal-Wallis and chi-square tests assessed differences in hygiene behavior frequency by gender. Negative binomial and logistic regressions were performed, accounting for socio-demographic characteristics. RESULTS/UNASSIGNED:= 0.0099) times the rate of weekly brushing than men in the full model; flossing frequency differences were not found. Men and women, whether ADA guidelines were met or not, identified similar brushing and flossing facilitators (health concerns, aesthetics), and barriers (lack of time, not being home). Some women (mothers) were motivated to brush to be role models for their children. Self-efficacy, or confidence in ability to brush or floss, was described differently by adults who met ADA guidelines (high self-efficacy) compared to the adults not meeting guidelines (low self-efficacy). CONCLUSIONS/UNASSIGNED:Integrating quantitative and qualitative data obtained from Mexican-origin adults identified few differences in both oral hygiene behaviors and the factors that influence their enactment.

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control of cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following the discovery that they predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting PCs. This VIP-SST disinhibitory circuit motif is observed throughout the neocortex from mice to humans, and serves as a key mechanism for top-down (feedback) and context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found to play an important role in sensory processing, control of executive functions, attention, sensorimotor integration and other cortico-cortical and thalamocortical feedback interactions. Furthermore, VIP INs have been implicated in mediating the effects of reinforcement signals, both reward and aversive, via their responsiveness to neuromodulators such as acetylcholine (ACh), and in facilitating synaptic plasticity and learning. While it is evident from transcriptomic analyses that VIP INs are a molecularly heterogeneous group, the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex by leveraging intersectional genetic approaches to study distinct VIP IN subtypes. We found that VIP INs can be divided into four different populations: a group that expresses the Ca²⁺-binding protein calretinin (CR), two distinct groups that express the neuropeptide cholecystokinin (CCK), and a group that does not express either CR or CCK (non-CCK non-CR; or nCCK nCR). VIP neurons in each group exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity, VIP/CR INs target almost exclusively SST INs, VIP/nCCK nCR INs also mainly target SST INs but also have connections to parvalbumin (PV) expressing INs. These two groups have essentially no connectivity to pyramidal cells (PCs). On the other hand, the two types of VIP/CCK INs target PCs, but differ in the degree to which synaptic release from each type is modulated by endocannabinoids. We also found that long-range inputs differentially recruit distinct VIP IN groups. Intriguingly, we find that distinct VIP IN populations target distinct SST INs subtypes in turn, indicating the presence of specialized VIP-SST disinhibitory subcircuits. Activation of distinct VIP IN subpopulations in vivo results in differential effects on the cortical network, thus providing evidence for modularity in VIP IN-mediated actions during cortical information processing.

After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to definitively confirm or refute a maladaptive role of contralesional TI in subacute motor recovery. We assessed 30 mild-to-moderately impaired subjects over the six months following ischemic stroke. We tracked contralesional TI and motor functions in the proximal and distal segments of the paretic UE. We used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP) in an arm and hand muscle. We used quantitative and clinical testing to examine deficits in muscle strength, motor control, and individuation; UE segmental impairment; and UE activity limitation. We assessed the relationships of contralesional TI to motor functions in the subacute period. Despite recovery of most motor functions in the proximal and distal UE, contralesional TI was largely static and unrelated to recovery of any motor function. There were inconsistent associations between stronger TI, less hand impairment, and less activity limitation in the subacute period overall. We found no compelling evidence to suggest a maladaptive role of contralesional TI in UE motor recovery in mild-to-moderately impaired stroke subjects. The scattered associations between stronger TI and better levels of paretic UE function suggest a potential supportive role rather than a limiting one. These findings challenge the validity of the interhemispheric competition model in the subacute recovery period, and prompt reconsideration of neuromodulatory strategies that subacutely target contralesional TI.

OBJECTIVES/OBJECTIVE:Home health care (HHC) plays a pivotal role in serving millions of US adults aging in place. Although the HHC population is growing rapidly in both size and diversity, driven by an aging US population and a changing demographic profile, there are increasing concerns of equity in HHC, particularly regarding how vulnerable populations are affected under current HHC practices. The purpose of this study was to examine the variations in accessing high-quality HHC in racial and ethnic minority groups and persons living with dementia. DESIGN/METHODS:Cross-sectional, secondary analysis. SETTING AND PARTICIPANTS/METHODS:Older adults who received HHC in 2016 from agencies with a star rating of overall care quality from the Home Health Compare program. METHODS:Start of care data from the 2016 HHC Outcome and Assessment Information Set was linked to Master Beneficiary Summary File, Home Health Compare, and Provider of Services file to address the aim. Multinomial regressions were used in analysis when risk-adjusting for individual and agency characteristics. RESULTS:Our risk-adjusted estimates, based on data from 574,682 older adults ≥65 years of age served by 8634 HHC agencies nationwide (2290 offering high-quality care, 4023 providing moderate-quality care, and 2321 delivering low-quality care), revealed significant disparities. Non-Hispanic Blacks (relative risk ratio, 0.62; 95% CI, 0.61-0.64) and Hispanics (relative risk ratio, 0.72; 95% CI, 0.70-0.74) were significantly less likely to receive care from high-quality agencies. Additionally, having dementia exacerbated disparities in accessing high-quality HHC between racial and ethnic minorities and White Americans. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:Racial and ethnic minority individuals face significant disadvantages in accessing high-quality HHC, with persons living with dementia from these groups being the most disadvantaged. Further research is warranted to investigate the referral and admission processes for HHC. Our findings highlight the need for actions from clinicians and policymakers to tackle potential biases in the aforementioned care processes.

This study introduces a unified computational framework connecting acoustic, speech and word-level linguistic structures to study the neural basis of everyday conversations in the human brain. We used electrocorticography to record neural signals across 100 h of speech production and comprehension as participants engaged in open-ended real-life conversations. We extracted low-level acoustic, mid-level speech and contextual word embeddings from a multimodal speech-to-text model (Whisper). We developed encoding models that linearly map these embeddings onto brain activity during speech production and comprehension. Remarkably, this model accurately predicts neural activity at each level of the language processing hierarchy across hours of new conversations not used in training the model. The internal processing hierarchy in the model is aligned with the cortical hierarchy for speech and language processing, where sensory and motor regions better align with the model's speech embeddings, and higher-level language areas better align with the model's language embeddings. The Whisper model captures the temporal sequence of language-to-speech encoding before word articulation (speech production) and speech-to-language encoding post articulation (speech comprehension). The embeddings learned by this model outperform symbolic models in capturing neural activity supporting natural speech and language. These findings support a paradigm shift towards unified computational models that capture the entire processing hierarchy for speech comprehension and production in real-world conversations.

Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-eosin-stained whole slide images (WSIs). We train an SSL Barlow Twins encoder on 435 colon adenocarcinoma WSIs from The Cancer Genome Atlas to extract features from small image patches (tiles). Leiden community detection groups tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival are confirmed in an independent clinical trial (N = 1213 WSIs). This unbiased atlas results in 47 HPCs displaying unique and shared clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analyses of these HPCs, including immune landscape and gene set enrichment analyses, and associations to clinical outcomes, we shine light on the factors influencing survival and responses to treatments of standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil additional insights and aid decision-making and personalized treatments for colon cancer patients.

BACKGROUND:HIV transmission and disease progression may be driven by associations HIV risk behaviors have with a constellation of alcohol, other substance, and mood-related conditions (CASM). However, observational study-based measures of these associations are often prone to unmeasured confounding. While meta-analysis offers a systematic approach to summarize effect sizes across studies, the validity of these estimates can be compromised if similar biases exist across studies. Our analysis assesses the likelihood that unmeasured confounding explains meta-analysis-derived measures of association between CASM and HIV risk behaviors, and provides bias-adjusted estimates. METHODS:We first conducted systematic reviews and meta-analyses to assess associations between CASM conditions and four HIV risk behaviors (medication non-adherence, unprotected sex, transactional sex, and multiple sexual partners). We then adjusted for potential unmeasured confounders using two methods designed for meta-analyses - Point Estimate and Proportion of Meaningfully Strong Effects methods. We selected "risk propensity" as an illustrative and potentially important unmeasured confounder based on the extant literature and mechanistic plausibility. RESULTS:In analyses unadjusted for unmeasured confounding, 89% (24/27) of odds ratios (ORs) show strong evidence of a positive association, with alcohol use and stimulant use emerging as dominant risk factors for HIV risk behaviors. After adjusting for unmeasured confounding by risk propensity, 81% (22/27) of ORs still showed strong evidence of a positive association. Associations between mood-related conditions and HIV risk behaviors were more robust to unmeasured confounding than associations between alcohol use and other substance use and HIV risk behaviors. CONCLUSION/CONCLUSIONS:Despite residual confounding present in constituent studies, there remains strong evidence of associations between CASM and HIV risk behaviors as well as the clustered nature of CASM conditions. Our analysis provides an example of how to assess unmeasured confounding in meta-analysis-derived measures of association.

OBJECTIVE:Preterm birth (PTB) remains one of the biggest public health challenges with both obstetric and perinatal implications. While a prior PTB is a known risk factor for recurrence, the understanding of the influence of factors such as race/ethnicity, gestational age, PTB subtypes, and interpregnancy intervals (IPI) remains limited. This study aimed to assess whether these factors modify PTB recurrence risk. METHODS:We conducted a retrospective cohort study of singleton pregnancies in Kaiser Permanente Southern California (2009-2022) using electronic health record data from 82,610 women with two pregnancies and 14,925 women with three. PTB subtypes, spontaneous (sPTB) and indicated (iPTB), were identified through natural language processing. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS:A first PTB was associated with a 6-fold increased risk of PTB in the second pregnancy compared to an uncomplicated pregnancy (23.29% vs. 4.98%, respectively; aOR, 5.60, 95% CI: 5.23-5.99). Those with a history of sPTB (aOR: 5.32, 95% CI: 4.87, 5.81) and iPTB (aOR: 8.26, 95% CI: 7.18, 9.50) had increased risk for the same respective subtype at their second pregnancy. PTB recurrence risk persisted across race/ethnicity categories. In women with PTB in both prior pregnancies, the risk for PTB in a third pregnancy was significantly higher (aOR 14.59, 95% CI 11.28-18.88). The recurrence of PTB between 1st and 2nd pregnancy was substantially higher for those who delivered at 20-33 weeks of gestation, regardless of PTB subtype. Non-Hispanic Black and Asian/Pacific Islander women had higher recurrence risk compared to non-Hispanic Whites. CONCLUSION/CONCLUSIONS:These findings highlight disparities in PTB recurrence by race/ethnicity and PTB subtype among a large integrated healthcare system in Southern California, underscoring the need for targeted interventions, particularly for sPTB.

IMPORTANCE/UNASSIGNED:The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments. OBJECTIVE/UNASSIGNED:To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative of chronic PTSD risk. Enrolled participants completed comprehensive clinical assessments and functional magnetic resonance imaging (fMRI) scans at 1, 6, and 14 months post trauma. Data were analyzed from September 2023 to March 2024. EXPOSURE/UNASSIGNED:Traumatic events included motor vehicle incidents, physical assaults, robberies, hostilities, electric shocks, fires, drownings, work accidents, terror attacks, or large-scale disasters. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Connectome-based predictive modeling (CPM), a whole-brain machine learning approach, was applied to resting-state and task-based fMRI data collected at 1 month post trauma. The primary outcome measure was PTSD symptom severity across the 3 time points, assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) PTSD symptom clusters (intrusion, avoidance, negative alterations in mood and cognition, hyperarousal). RESULTS/UNASSIGNED:A total of 162 recent trauma survivors (mean [SD] age, 33.9 [11.5] years; 80 women [49.4%] and 82 men [50.6%]) were included at 1 month post trauma. Follow-up assessments were completed by 136 survivors (84.0%) at 6 months and by 133 survivors (82.1%) at 14 months post trauma. Among the 162 recent trauma survivors, CPM significantly predicted PTSD severity at 1 month (ρ = 0.18, P < .001) and 14 months (ρ = 0.24, P < .001) post trauma, but not at 6 months post trauma (ρ = 0.03, P = .39). The most predictive edges at 1 month included connections within and between the anterior default mode, motor sensory, and salience networks. These networks, with the additional contribution of the central executive and visual networks, were predictive of symptoms at 14 months. CPM predicted avoidance and negative alterations in mood and cognition at 1 month, but it predicted intrusion and hyperarousal symptoms at 14 months. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this prognostic study of recent trauma survivors, individual differences in large-scale neural networks shortly after trauma were associated with variability in PTSD symptom trajectories over the first year following trauma exposure. These findings suggest that CPM may identify potential targets for interventions.