# data[].attributes.title
The impact of dyadic processes on smoking and cigarette craving: An experimental investigation of romantic partners and smoking friends

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Smoking is the leading preventable cause of cancer and mortality in the US, with Covid hitting smokers especially hard. Quitting is difficult (and smoking increased during Covid), yet interventions yield only mixed success. Smokers often smoke and crave cigarettes in social settings. Public health research emphasizes social factors in smoking, and clinical studies point to the need to better understand disrupted relationship dynamics when a romantic partner or friend quits. Thus, it is striking that nearly all lab research (testing causal relations) on smoking and craving tests smokers in isolation. This neglect of social factors extends to quitting practices. Even on the most respected websites, the “social” advice for quitting offers fairly simplistic and incomplete tips that fail to consider subtle yet powerful challenges that quitting may create for smoking friends and romantic partners. Further, there is no evidence regarding how social factors exacerbate the altered smoking-related decision-making that accompanies craving, thus raising the likelihood of smoking. To develop a comprehensive understanding of the factors and processes that maintain smoking and increase relapse risk, basic experimental research that integrates social processes into existing paradigms focusing on pharmacologic and (individual) psychological aspects of addiction is needed. This basic experimental study with humans (BESH) application addresses targeted NCI Behavioral Research Program priorities focused on leveraging research on dyadic processes to examine health-related behaviors such as smoking cessation. Integrating theory and research derived from three disciplines rarely applied to smoking (experimental social psychology with a focus on dyadic processes, affective science, cognition), the project will offer a multimodal analysis of craving and smoking in two social contexts relevant to smoking (friendships, romantic couples). This project will use innovative measures of affect (e.g., an urge pressure dynamometer, speech volume, Facial Action Coding System) and decision-making to test theoretically-derived processes (e.g., shared reality, motivated reasoning, emotional contagion) that may help explain the challenges linked to quitting when rewarding social aspects of smoking are lost. The project will elucidate why some smokers may struggle managing relationships when quitting, and why social interventions may be most useful for a subset of smokers. In both a friends study and a couples study, abstinent daily and nondaily smokers will be recruited. The friends study will test the impact of a friend’s presence on cue-elicited craving, with a focus on shared craving states, and the couples study will target effects of mutual smoking versus unilateral smoking on critical social interactions and relationship perceptions thought to raise obstacles to quitting. This project will test important social-cognitive and socio- emotional mechanisms underlying craving and smoking that may identify hidden social motives for smoking that must be integrated into biopsychosocial smoking treatment. Regardless of outcome, this work will provide valuable data on emotional and cognitive processes experienced in social settings during craving and smoking.

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Expanding access and impact of tuberculosis preventive therapy: Community-friendly delivery and monitoring of TPT to improve uptake and reduce TB transmission

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National Institute of Allergy and Infectious Diseases (NIAID)

# data[].attributes.abstract
Enter the text here that is the new abstract information for your application. International and Kenyan guidelines recommend TB preventive therapy (TPT) for people with HIV (PWH) and other people at high risk for TB, including close contacts of people with TB. Despite the evidence for reduced morbidity and mortality for people with HIV (PWH) who receive TPT, and guidelines recommending use, there remains a substantial gap between people recommended to receive and people who actually receive and complete a course of TPT. The 2022 WHO Global TB Report highlighted the growing gap in access and provision of TPT, which has been aggravated by the COVID-19 pandemic. Bridging this gap is a Kenyan and global priority. With the recent availability and evidence for newer, shorter regimens of TPT, a transformation of HIV care delivery models (in part forced by the COVID-19 pandemic) and evolving national guidelines for TPT, it is increasingly urgent to explore new person-friendly models of TPT delivery to inform programmatic guidance that results in greater uptake, adherence, and completion of TPT. HIV care transformed to adopt “differentiated service delivery” (DSD) models, which encourage community-delivered care, infrequent clinic/facility visits, multi- month dispensing, limited laboratory monitoring, and task-shifted treatment models to deliver comprehensive HIV care to stable adults in community settings. These successful models for differentiated HIV care delivery may be able to be adapted to include TPT. The availability of safe, effective, short-course TPT (i.e. 3HP, 3HR) with limited monitoring requirements suggests that similar community-based and multi-month dispensing models may be adapted to scale essential TPT to populations who most need it, including PWH, young child contacts, and all household contacts of people with TB. We will explore two approaches of adapting HIV differentiated services to TB prevention. We hypothesize that people who receive differentiated TPT delivery have higher rates of completion of a course of TPT than people who receive standard-of-care clinic-based TPT. We will 1) conduct a randomized controlled trial of DSD care (multi-month dispensing) vs. clinic standard-of-care TPT delivery in two priority populations for TPT in Kenya: household contacts of people with TB and PWH, 2) investigate the impact of DSD TPT on household and community TB transmission with follow-up testing and mathematical modeling, and 3) examine preferences, barriers and facilitators of TPT completion and TPT implementation using qualitative research. Together, this research will establish the foundation for implementation studies of optimized patient and community-friendly, differentiated TPT delivery approaches to increase TPT uptake and completion in Kenya and ultimately decrease morbidity, transmission, and mortality from TB.

# data[].attributes.title
Structural and mechanistic study of bat NLRP6 inflammasome in detecting RNA viruses

# data[].attributes.funder_divisions[]
National Institute of Allergy and Infectious Diseases (NIAID)

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Bats harbor the unique ability to host a wide array of emerging viruses, such as Ebola virus, Nipah virus, Hendra virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). These RNA viruses are highly pathogenic and often lethal to humans and animals. Intriguingly, bats develop no/minimal signs of diseases in both natural and experimental infections. Significant progress has been made to suggest the altered immunological networks and dampened inflammatory signaling in bats. However, the direct viral sensing mechanisms in bats and the unique immunological features that distinguish bats from other mammals remain poorly studied.  Inflammasomes are multi-protein signaling platforms that form in epithelial cells and myeloid cells upon stimulation by pathogen and damage signals. Their primary function is to active the inflammatory caspases such as caspase-1. Canonical inflammasome sensors consist mainly of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing (NLR) family proteins. Among these NLR proteins, NLRP6 is a unique pattern recognition receptor that is predominantly expressed in intestinal and liver system. The inflammasome function of NLRP6 has been reported to directly detect the RNA viruses (rotavirus and mouse hepatitis virus) that infect the gastrointestinal (GI) tract. On the other hand, the excessive activation of NLRP6 inflammasome may exacerbate the tissue damage and cause the autoinflammatory diseases. In bats, the GI tract represents one major organ for viral infection, while infections rarely cause symptoms. The long-term goal of our project is to understand the specific inflammasome sensing mechanisms in detecting RNA viruses in the intestinal epithelium of bats and gain the insights of how bats protect themselves from the pathogenesis of inflammation-induced intestinal barrier dysfunction.  In this application, we propose to pursue the following specific aims: 1) Determine the cryo- EM structures of bat NLRP6 monomer, elucidate the biochemical foundation of bat NLRP6- dsRNA interaction, determine the cryo-EM structures of bat NLRP6 with viral dsRNA and compare the structural mechanisms of dsRNA sensing and inflammasome signaling among bat, mouse and human NLRP6; 2) Elucidate the RNA virus-induced bat NLRP6 inflammasome signaling in reconstituted intestinal epithelial cells (IECs), analyze the bat inflammasome signaling in Eonycteris spelaea (Es) in response to bat-borne RNA viruses, study the genetic role of bat NLRP6 in regulating inflammasome signaling in bat primary IECs/bat intestinal organoids. The proposed studies will guide the development of therapeutics to target GI inflammatory disorders in human based on the molecular details of bat NLRP6 inflammasome.

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Middle East Respiratory Syndrome Coronavirus

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PRECISE: accessible sample-to-answer RT-PCR detection of hepatitis C infection from whole blood

# data[].attributes.funder_divisions[]
National Institute of Allergy and Infectious Diseases (NIAID)

# data[].attributes.abstract
This proposal is in response to NOSI NOT-AI-23-001, which calls for new point-of-care HCV diagnostics. Most of global HCV burden is concentrated in low- and middle-income countries (LMICs), but the U.S. has witnessed a steady increase in infection rates in the past decade, with an estimated 140,000 new cases annually. Whereas direct-acting antivirals (DAAs) can over 95% of HCV-infected individuals, and are becoming more accessible, about 40% of infected people are unaware of their status. The current two-step diagnostic process requires an initial antibody screen followed by an expensive and time-consuming RNA test to confirm active infection. This cumbersome workflow requires multiple office visits for patients, resulting in delays in treatment initiation and significant patient follow-up loss.  Our lab has been developing plasmonic-based thermocycling into a clinically useful method for fast multiplexed RT-PCR at the POC. In this approach, heating is achieved not externally via the Peltier effect, but rather internally via infrared excitation of nanoparticles; as a result, the heating is rapid, and powered with low- power robust optical components. We have gathered substantial preliminary data to validate the premise of this approach to work on clinical specimens (saliva and nasal swabs); the results (published in Nature Nanotechnology, 2022) showed the ability, within 25 minutes from sample to result, to detect SARS-CoV-2 with high sensitivity and specificity. Moreover, even in the presence of the plasmonic nanoparticles, we showed that real-time qPCR could be performed with accurate quantitative determinations of cycle threshold (Ct) values. This capability for sample-to-result analysis is faster than traditional PCR approaches using Peltier heating, and the instrumentation using readily available optics renders the approach suitable for community testing sites where rapid and accurate results are sought.  This proposal integrates plasmonic PCR with plasma filtration (starting with whole blood) and magnetic bead-based nucleic-acid extraction (a technique we recently published called PRECISE, Lab Chip, 2024). The proposed combined method, PRECISE plasmonic PCR, takes advantage of special nanoparticles to facilitate a seamless sample-to-result workflow for the end user, suitable for the target community health settings to facilitate HCV diagnosis in a single patient visit to enable on-the-spot treatment. The target metrics would be the best in class among HCV nucleic-acid tests, meeting all of the criteria in the target product profile recommended by the NOSI for an “optimal” test except for the 15-minute turnaround time (our target is 30 minutes), and surpassing all “minimal” targets. The target metrics include cost considerations.

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Reverse Transcriptase Polymerase Chain Reaction

# data[].attributes.title
Empowering Cardiovascular Health in Custodial Grandparents (ECG)

# data[].attributes.funder_divisions[]
National Heart Lung and Blood Institute (NHLBI)

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There has been a steady increase in grandparent caregiving in the US. This acceleration is due to recent trends in domestic violence, parents’ incarceration, parents’ death due to the COVID-19 pandemic, and opioid overuse that increase familial instability and leave more grandchildren to be cared for by custodial grandparents. These grandparent caregivers face ongoing stressors as they navigate legal custody arrangements, cope with loss of their own child(ren), or face social isolation. A higher prevalence in an array of social determinants of health often put them at higher risk for cardiovascular disease (CVD): belonging to a racial/ethnic minority, living below the poverty line, living in single-caregiver households, and having lower levels of educational attainment. Additionally, custodial grandparents appear to have higher rates of adverse childhood experiences, another known risk for CVD. This unique mixture of stressors manifests in custodial grandparents’ health, where they are at higher risk for CVD compared to their non-caregiving peers. However, there is a dearth of intervention addressing custodial grandparents’ CVD risk. To address this gap and optimize healthy aging and cardiovascular health among this growing at-risk population, we will implement a virtually delivered, evidence-based CVD risk reduction intervention - The Rural Caregiver Heart Health Education [RICHH] Intervention. The RICHH intervention was originally targeted for adult caregivers of adult family members with a chronic illness, and has not been tested in the context of custodial grandparents’ CVD risk. We propose a 3-year planning project to determine the feasibility, acceptability, and initial effect of the RICHH intervention conducted with custodial grandparents. We will employ a mixed method design and conduct a 2-arm randomized controlled trial with 70 custodial grandparents in Oregon. The specific aims are: 1) modify the RICHH intervention to target custodial grandparents from a variety of backgrounds; 2) employ the re-designed intervention and assess its feasibility and acceptability; and 3) evaluate and refine the RICHH protocol among our team members and explore the initial effect of the intervention based on measures of CVD risk, self- management behaviors, and depressive symptoms at 4-months and at 6-months, compared to baseline. Expected outcomes are to complete the sufficient and scientifically necessary groundwork to support a future clinical trial that will test the effectiveness of the RICHH intervention with a longer follow-up and increased inclusivity of participants from marginalized populations, with the objectives of: a) preventing CVD-related morbidity and mortality and overall physical decline, b) improving psychological well-being in these grandparents, and c) fostering a more heart-healthy environment in grandfamilies.

# data[].attributes.title
Investigating Histone Acetylation Modulator Function in Alveolar Regeneration and Disease Pathogenesis

# data[].attributes.funder_divisions[]
National Heart Lung and Blood Institute (NHLBI)

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Influenza and COVID-19 remain significant global health concerns, with viral infections in the lungs often leading to alveolar damage and, in severe cases, progressing to acute respiratory distress syndrome (ARDS). ARDS development is closely linked to impaired alveolar regeneration, which relies on the proliferation and differentiation of alveolar type 2 (AT2) stem cells into alveolar type 1 (AT1) cells to restore lung function. The precise molecular mechanisms that govern alveolar regeneration remain poorly understood. Here I have established a high-throughput in vivo genetic screening system in mice to systematically search for essential epigenetic modulators that contribute to alveolar regeneration. Preliminary results have identified numerous histone acetylation pathway related genes, including lysine acetyltransferase 8 (Kat8), are required for AT2 restoration and may contribute to differentiation towards AT1 cells. Kat8 has not previously been linked to alveolar regeneration, however, a key component of its associated protein complex and downstream target genes has been identified in genome-wide association studies as risk genes for idiopathic pulmonary fibrosis, a deadly disease also caused by impaired alveolar regeneration. This proposal aims to clarify the mechanisms by which Kat8 regulates alveolar regeneration, determine the association of Kat8 loss of function with pulmonary fibrosis and further enhance the existing in vivo screen system by integration with single cell techniques to comprehensively map other histone acetylation modulation functions. This study will shed light on epigenetic mechanisms underlying AT2-mediated alveolar regeneration and disease pathology, with the potential to inform the design of novel therapeutic approaches targeting histone acetylation modulators to promote alveolar regeneration and combat fibrosis progression. The proposed research plan will be executed at the Broad Institute of MIT and Harvard, Cambridge, under the mentorship of Dr. Fei Chen and Dr. Jayaraj Rajagopal, with overall complementary expertise in the field of genomics, synthetic biology, and lung stem cell biology. My career objective is to become a tenure-track faculty pioneering and simultaneously training next-generation scientists at the intersection of technology and lung stem cell biology. To accomplish my career goals, I have put together a comprehensive training plan to enhance the overall skill sets required to establish myself as a successful independent investigator. To ensure timely progress toward fulfilling my rigorous research plan and career goals, I have gathered an expert advisory committee comprising Dr. Carla Kim, Dr. Darrell Kotton, Dr. Jason Buenrostro, and Dr. Ruth Franklin, with whom I will regularly discuss my research progress and receive invaluable career development guidance, the key ingredient to my pathway to scientific independence.

# data[].attributes.title
Statistical Methods for Information Synthesizing Using Multiple Existing Longitudinal Cohort Studies

# data[].attributes.funder_divisions[]
National Heart Lung and Blood Institute (NHLBI)

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Building on the valuable groundwork laid by the Collaborative Cohort of Cohorts for COVID-19 Research (C4R), this research project aims to advance the statistical methods used in pooled cohort studies. Pooled cohort studies are a powerful tool in clinical and epidemiological research, enabling the detection of subtle effects and interactions and improving the generalizability of findings through increased sample diversity. However, they pose unique challenges, particularly systematic missing data and potential heterogeneity across studies. Our goal is to address these challenges and improve the robustness of pooled cohort studies. To achieve this goal, we have structured four specific aims: Under Aim 1, we propose a novel Generalized Method of Moments (GMM) framework for robust statistical inference across multiple studies dealing with systematically missing data. Our investigation will probe into the missing data mechanism across multiple samples, employing density ratio weight- ing to handle the heterogeneity in covariate and outcome distributions. Under Aim 2, we propose nonparametric predictive models that leverage data from multiple studies with systematically missing data. We will develop a gradient boosting algorithm for versatile prediction model accommodating predictors of varying detail. Addition- ally, we will design algorithms for cohort-specific prediction models that take advantage of information from other cohorts. Aim 3 extends the proposed methods for systematically missing data and cohort heterogeneity to right- censored time-to-event data. Under Aim 4, we perform comprehensive evaluations through simulations and real data analyses, and develop user-friendly analytical pipelines for the proposed methods. Our research design and methods are centered around developing, testing, and refining these new statistical methods. These methods will then be evaluated both via simulation and real-world application to the C4R data. The long-term objective is to establish reliable tools for integrating multiple cohorts and conducting individual participant data meta-analysis. The development of these robust statistical methods and a systematic pipeline for the pooled analysis of system- atically missing data will provide valuable tools for researchers working with pooled cohort data. This project will enhance the validity and reliability of findings from the C4R study, and thereby contribute to a more accurate un- derstanding of risk and resilience factors for COVID-19 severity and outcomes. Our findings will be disseminated widely, including the development of user-friendly software to facilitate the application of our proposed methods.

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National Heart  Lung  and Blood Institute

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United States National Institutes of Health

# data[].attributes.title
Health, Mortality, & Aging Among People with Criminal Legal System Contact in America

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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PROJECT SUMMARY/ABSTRACT:  Criminal justice contact is an important contributor to population variation in health outcomes, including mortality, morbidity, and aging. During and following the COVID-19 pandemic, people in American jails, prisons, and detention centers experienced elevated health risks that exacerbated their already high morality and aging precariousness. This proposal requests support for a three-year conference program on, “Health, Mortality, and Aging Among People with Criminal Legal System Contact in America,” with each year focusing on critical questions about the health of incarcerated people that have emerged since the COVID-19 crisis. These interdisciplinary conferences will harness the research and expertise of established and emerging scholars conducting research at the intersections of health, mortality, and aging in economics, sociology, demography/population science, law, criminology, public health, medicine, and public policy. The proposed conference programs are innovative by including the participation of people affected by legal system involvement, as well as by investigating population heterogeneity to formulate and to advance a bold new research agenda that will benefit affected communities. The program has four specific aims: (1) to advance scientific knowledge and research recommendations to improve health across the life-course for people involved in the criminal legal system; (2) to amplify the voices of affected people, families, and communities; (3) to train the next generation of criminal legal scholars; and (4) to engage multiple audiences. Deliverables will include: (1) three special issues, each devoted to a unique conference theme over the three years (i.e., mortality, health, and aging), allowing for the discrete and unique treatment of each topic; and (2) research briefs that translate findings into potential interventions and recommendations that broadly engage the individuals, families, and communities subject to criminal justice contact, as well as other stakeholders (government officials, prison and court actors, non-profits, and other advocates). By discussing and documenting how life-course transitions that intersect with the criminal legal system matter for socio-economic, health, and well-being, this conference will engage and advance the conceptual and empirical dialogues that began with several National Academies of Sciences, Engineering, and Medicine workshops in 2013 and 2020, and, more recently, a half-day seminar in 2024. As leaders in the criminal legal field, the investigative team and Cornell University are uniquely positioned to host this program.

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United States National Academy of Sciences

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Building Reliable Vision-Language Assistant for Dermatology AI through Modeling Uncertainties in Multimodal LLMs

# data[].attributes.funder_divisions[]
National Institute of General Medical Sciences (NIGMS)

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Diagnosis delay is one of the key factors that lead to skin cancer death, especially for melanoma diagnosis during the COVID-19 pandemic. The long examination time and limited dermatological access have been the major roadblocks to the preventive treatment of skin cancers to lower the high mortality rate. Developing a clinical AI agent that can analyze digital skin images and provide timely, interactive text responses to patient symptoms and inquiries will signiﬁcantly mitigate the nationwide dermatologist shortage, thereby improving the early diagnosis chance and teledermatology accessibility for melanoma as well as other skin diseases. Conventional dermatology AI methods mainly focus on medical image recognition to identify skin lesions and malignancies, falling short in visual-language assistance for remote healthcare services. A conversational diagnostic AI model, which is able to answer medical questions by sensing subtle visual patterns of skin disorders/cancers, is still in urgent need. The long-term goal of this research program is to develop a reliable large visual-language (VL) model that enables conversational Dermatology AI to facilitate early melanoma diagnosis and general skin care. The proposed research will generate accurate and interpretable clinical responses by ﬁnetuning Large Language Models – LLMs (e.g., the generative AI models deployed in ChatGPT) through answering questions and visual reasoning in multimodal contexts. Speciﬁcally, the project will realize three aims: 1) Build a new multimodal LLM speciﬁcally for dermatology to discern melanoma and other skin diseases and to automatically answer questions relevant to skin lesions. 2) Study uncertainties stemming from data bias and distribution shifts to enhance the reliability of LLM-powered AI diagnosis in multimodal contexts and teledermatology environments. 3) Determine the visual relevance in LLM decisions based on the rich public dermatological images with clinical text annotations. The proposed research will establish a new multimodal LLM that interweaves visual reasoning and uncertainties to advance Dermatology AI in broad VL assistance tasks, enabling automatic conversational diagnostic in teled- ermatology and providing new insights about how LLM understands skin lesions and dermatological knowledge. A pixelwise visual instruction tuning approach and a novel multi-level uncertainty quantiﬁcation framework will be developed, providing technical foundations to beneﬁt a wide range of LLM-based healthcare research. This project will be the ﬁrst large visual-language research study that investigates LLM's intelligence and reliability in coping with multimodal dermatology contexts – visual skin lesions and text clinical annotations/dialogues. The success of this project will provide transformative AI techniques in assisting early melanoma diagnosis and remote skin care, leading to better teledermatology accessibility for patient treatments, reducing mortality from skin cancers through timely detection, and revolutionizing dermatological access in public healthcare systems.

# data[].attributes.title
Novel Statistical Methods for Confounded and Incomplete Network Data

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National Institute of Allergy and Infectious Diseases (NIAID)

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Studies of public health interventions aimed at controlling the spread of infectious diseases such as HIV/AIDS or COVID19 often face important methodological challenges due to pervasive network dependence, confounding and widespread missing data. Each of these complications has separately received considerable attention, however, methods to tackle them when they coexist are currently lacking. We will develop new statistical methodology, specifically causal identification theory and robust estimation theory which we plan to apply to address pressing scientific questions in infectious disease research using data from two randomized trials and two observational studies with data at hand, where both missing data, and network structure occur including the HAALSA South African Study, the Networks, Norms, and HIV/STI Risk Among Youth (NNAHRAY) study, and the Botswana Combination Prevention Study (BCPP) and the Home-based Interventionto Test and Start (HITS) cluster randomized trial. Success in the proposed research will not only allow for robust conclusions to be drawn from data in the above studies, despite the presence of missing data, the potential for confounding bias, and complex social network structure; it will also provide a methodological template for addressing similar questions beyond these four studies as confounded, missing and dependent data are routinely co-occurring complications in Social and Infectious Disease Epidemiology.