# data[].attributes.title
Telehealth-Delivered tDCS for Cannabis Addiction Recovery: The C.A.R.E.S. (Cannabis Addiction Recovery Enhancement Stimulation) Initiative

# data[].attributes.abstract
Cannabis use in the U.S. has surged, driven by widespread legalization and accelerated by the COVID-19 pandemic. Over 55 million U.S. adults are current users, and approximately 30% will develop cannabis use disorder (CUD). Despite the urgent need for effective treatments, no FDA-approved options exist, and current interventions have proven insufficient, underscoring the necessity for innovative and accessible solutions. We propose a novel, home-based intervention combining transcranial direct current stimulation (tDCS) with mindfulness meditation, targeting the dorsolateral prefrontal cortex—a key region in the neural circuitry underlying the addiction cycle. Delivered via the ElectraRx telehealth portal, this approach is both cost-effective and widely accessible. Our extensive preliminary data, involving over 600 patients and 17,000 home-based tDCS sessions, along with our pilot study of this intervention in CUD, demonstrate its feasibility and potential. However, further development and testing are required to advance it to clinical use. The initial UG3 phase (Years 1-2) will involve developing a tDCS home-based administration system by Soterix Medical Inc. (SMI), tailored specifically for the intended population and environment ("ElectraRx-CARES"). We will then refine and validate the tDCS-mindfulness intervention through a double-blind, sham-controlled feasibility trial with n = 46 adults with CUD. If at least 50% of participants complete 70% of the sessions, we will advance to the UH3 phase, where a large-scale RCT enrolling n = 192 participants with CUD to assess the intervention's efficacy in reducing cannabis use and withdrawal symptoms. Follow-up assessments at three months will evaluate the persistence of these effects. FDA guidance on device development and data collection will be obtained throughout. Finally, we will optimize intervention delivery, iterate the device, and advance the regulatory process, including pursuing Breakthrough Device Designation. This scalable intervention addresses a critical public health need and represents a promising step forward in treating the rapidly growing problem of CUD.

# data[].attributes.title
Structural studies of the full-length nucleocapsid protein of SARS-CoV-2

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

# data[].attributes.abstract
The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The nucleocapsid (N) protein of SARS-CoV-2 plays several functionally critical roles in the life cycle of the virus, similar to those in other coronaviruses. It assembles with the genomic RNA into an RNA- protein complex, which is packaged into virions. The protein also forms a replication-transcriptional complex with the RNA synthesis machinery to create replicating organelles for efficient transcription and replication. It protects viral double-stranded RNA (dsRNA), which would otherwise be degraded by the RNA interference (RNAi)-based antiviral immune defense mechanism in the host cells. N protein adopts a modular architecture with two well- folded domains, including N-terminal domain (NTD) and C-terminal domain (CTD), which are flanked by three intrinsically disordered regions. Crystal structures of the NTD and CTD have been determined, but high- resolution information of the full-length N protein, in particular, in complex with RNA is still lacking. We hypothesize that intrinsically disordered regions of the N protein from SARS-CoV-2 adopt defined structures when bound to RNA that are critical for viral assembly and replication. In this project, we plan to determine the high-resolution structure of the full-length N protein in complex with the viral RNA by cryogenic electron microscopy (cryo-EM). The goal is to visualize detailed structural features of the full-length N protein in the context of RNA to advance our understanding of its function and to inform development of intervention strategies. Our specific aim is to obtain a high-resolution structure of intact SARS-CoV-2 N protein in complex of RNA.

# data[].attributes.title
The evolutionary genetic basis for changes in viral receptor-binding specificities

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

# data[].attributes.abstract
In this proposal, I discuss my plans to use a high-throughput yeast display platform to dissect the essential changes that occur in viral protein binding specificities. I am using the coronavirus family for my investigations because there are instances of species specificity changes of interest in the SARS-related coronaviruses that are of interest, as well as instances of wholesale receptor changes in the MERS-related coronaviruses. Thus far, this work has begun to find the substitutions of interest along the gains of human ACE2 binding in the SARS-related coronaviruses. From preliminary results, we can see one substitution that is highly associated with mutations that can bind human ACE2. In addition, I have started to parse out the important branch where the wholesale receptor change occurred along the MERS-related coronavirus family phylogenetic tree. These changes are particularly interesting because the evolutionary genetic basis for these receptor-binding specificity changes has not been characterized. Through this research, I will inform the field of the necessary changes that need to occur for viruses to switch receptors as well as what effects species specificity has on these receptor binding dynamics. Overall, this work will be important for the field, too, because it will lay a foundation of how these viruses are gaining the ability to spillover from their animal reservoirs and into humans. Zoonotic transmission, or viruses gaining the ability to bind human receptors, is a major threat to human health, as we know from the SARS-CoV-2 pandemic and the MERS epidemic, for instance.

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Episodic Memories of 9/11 terror attack and Mental Health: Natural Language Processing of Adolescent and Adult Survivors' narratives (EMLAS study)

# data[].attributes.funder_divisions[]
National Institute for Occupational Safety and Health (NIOSH)

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NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

# data[].attributes.abstract
The mental health effects of the World Trade Center (WTC) attacks on adults first responders and survivors are well-documented, with elevated rates of PTSD, depression, and anxiety. However, less research has focused on how the 9/11 attacks impacted children and adolescents who were exposed to the trauma. While PTSD was less common in these younger populations, studies suggest they experienced heightened anxiety, particularly separation anxiety, and other emotional disturbances. Furthermore, the onset of symptoms in this age group often emerged later, highlighting the need to explore the delayed effects of trauma across developmental stages. Adolescence is a critical period of emotional, social, and cognitive development, and trauma during this time can disrupt these processes, leading to long-term impairments in executive function, emotional regulation, and memory. Therefore, adolescents may be more vulnerable to the enduring effects of trauma, which can manifest in adulthood through poor coping mechanisms, emotional blunting, identity challenges and mental health disorders. Given that the 9/11 attacks occurred nearly 25 years ago, we will use memory recollection as means to understand current mental health status of those who were adolescents at the time of 9/11 attack. Our approach is based on the understanding that traumatic memories are often encoded differently from non-traumatic ones due to the brain’s heightened stress response, making them difficult to forget and more emotionally charged. These memories play a critical role in shaping long-term mental health, contributing to conditions such as PTSD, depression, and anxiety. Additionally, autobiographical memory, particularly in trauma, can be fragmented, emotionally intense, and less contextually anchored in younger individuals. The proposed research aims to use Natural Language Processing (NLP) to analyze the spoken narratives of 9/11 survivors, comparing those who were adolescents at the time of the attacks to adults. NLP has proven to be a powerful tool in mental health research, identifying linguistic and emotional markers indicative of psychological distress. By comparing 9/11 narratives with those related to more recent traumas, such as the COVID-19 pandemic, when all participants were adults, we can assess how developmental stages at the time of trauma influence memory recall and how is related to current mental health. Ultimately, this research seeks to identify distinct narrative markers that correlate with mental health outcomes, contributing to the understanding of how trauma experienced at different developmental stages impacts long-term psychological well-being. This approach has the potential to inform future interventions, enabling more personalized targeted treatment for trauma survivors to improve mental health outcomes.

# data[].attributes.title
High parameter fluorescence activated cell sorter

# data[].attributes.abstract
The Versiti Blood Research Institute (VBRI) is an academic hematology research center located in Milwaukee, WI. The VBRI Flow Cytometry Core serves the needs of scientists at the VBRI, the Medical College of Wisconsin (MCW), and the Children’s Research Institute (CRI), three research-heavy institutions assembled on the Milwaukee Regional Medical Campus (MRMC). Currently, a heavily oversubscribed Cytek Aurora in the CRI is the only high parameter cell sorter on the MRMC. The VBRI’s 15-year old FACS Aria can no longer support the sophisticated sorting needs of many MRMC users and will need to be replaced in anticipation of BD’s discontinuation of servicing the product line. To address these deficiencies, we are requesting funds to purchase a Becton Dickinson Symphony S6 SE, a 5-laser, 49-detector cell sorter. The Symphony S6 matches the Symphony A5 SE analyzer purchased by VBRI in 2022, allowing for seamless transfer of multi-color panels from analysis to sorting. The research projects of our nine Major and eight Minor NIH-funded users require high parameter cell sorting to accomplish their goals. Using the Symphony A5 SE analyzer, these investigators have acquired valuable expertise in spectral flow cytometry, and the acquisition of a Symphony S6 will enable them to overcome critical roadblocks in their research. VBRI research will broadly benefit from this new instrument. In immunology, development of a B cell therapeutic for multiple sclerosis, the delineation of B cell involvement in heparin-induced thrombocytopenia as well as clarifying the mechanism of thrombotic complications in COVID- 19 all require access to high parameter sorting, using panels already established on the Symphony A5 SE. Major Users focused on hematologic malignancies require rapid access to a multi-parameter cell sorter to isolate rare cell populations from primary leukemia samples that can arrive any time. A signature program studying the role of the glycome in hematopoiesis is critically dependent on the Symphony S6’s increased number of channels. In thrombosis and hemostasis, studies on cellular integrins, kindlin signaling in neutrophils and platelets, and the pathophysiology of fetal/neonatal alloimmune thrombocytopenia will all heavily use the Symphony S6. Moreover, the Symphony S6 will overcome critical bottlenecks for MCW researchers studying the role of exosomes in ovarian cancer, chronic pain in Fabry and sickle cell disease, gamma herpesvirus associated B-cell lymphomas, immune response to radiation exposure and type I diabetes. FACS is an integral part of the workflow of most VBRI faculty and many researchers at MCW and CRI. Currently available high parameter (>20) sorting capacity is extremely limited, slowing progress on NIH-funded research. Even lower parameter sorting capacity is becoming limited on the MRMC as BD FACS Aria instruments are approaching end of lifespan. The Symphony S6 will provide essential high parameter sorting capacity for several NIH-funded projects, and dramatically accelerate progress on others. Ease of panel transfer, economic use of precious samples, and complementarity to existing instrumentation will expedite research progress to ascertain a high return on investment.

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United States National Institutes of Health

# data[].attributes.keywords[]
fluorescence activated cell sorter device

# data[].attributes.title
Investigating the development and regulation of the extrafollicular B cell response as a programmed response type

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

# data[].attributes.abstract
This is a proposal to advance our basic understanding of a critical but understudied aspect of immunity—the extrafollicular (EF) response. Upon activation, B cells enter either the EF response, or the germinal center (GC) response. The GC gives rise to high affinity memory B cells and long-lived plasma cells (PC), crucial elements of vaccine responses. While the GC is highly studied, the role of the EF response and how it is generated is much less well understood. Yet, the biology of the EF response is likely to be highly relevant to human health: Recent studies highlight the importance of the EF response, both in controlling infection and in dysregulated contexts such as Lupus and severe COVID infection. We have recently identified IL-12 as an upstream cytokine switch that directs B cells toward the EF response and suppresses GCs. In B cells, IL-12 induces autocrine feed-forward signaling between IL-12 and IFNg, resulting in distinct transcriptional changes and enhanced PC differentiation. B cells secrete IL-12, which promotes both their own differentiation and surprisingly, early TH1 differentiation. IL-12/IFNg signaling also induced the expression of CXCR3 by B cells, known to facilitate DC:T cell interactions during TH1 responses. DCs have also been shown to enhance PC differentiation in some contexts. EF foci form in locations rich in DCs and T cells, but the significance of this location is unknown. These findings lead to our central hypothesis - that the EF response is a specialized “response type” preferentially supporting rapid expansion and PC differentiation, and that EF foci are a niche with local cell-cell interactions and cytokine production, coordinated by inflammation-induced chemokines. GC B cells facilitate the differentiation of TFH, and though naïve B cells can invade existing GC, the bulk of the GC population is maintained through proliferation with infrequent differentiation. In Aim 1, we will test the role of B cells in enhancing the EF response locally, and test the self-renewal capacity of the undifferentiated “EF B cell” population. In Aim 2, we will isolate the continually proliferating EF B cell population and begin to characterize the EF B cell state transcriptionally and epigenetically. We will examine the effects of IL-12 and IFNg on this gene regulatory network. We will also target transcription factors that are predicted to regulate the EF B cell program and test these findings using human B cells. In Aim 3, we will characterize the EF foci as a niche, much like the GC is thought of, using spatial transcriptomics and genetic approaches to define the roles of DCs, CD4 T cells, and CXCR3 in the EF response. Collectively these studies will provide a significant conceptual advance for our understanding of the EF B cell response and enable the creation of new tools to study EF B cells and their progeny. This is an area of great need as relatively little is known about how the EF response is regulated. These studies are therefore poised to have a significant impact in advancing our understanding of the EF response, with a long-term objective of learning how to both restrain EF responses to treat EF-driven autoimmunity, and exploit the EF response for novel vaccine designs and cancer therapeutics.

# data[].attributes.keywords[]
Structure of germinal center of lymph node

# data[].attributes.title
Antibody feedback on B cell response to vaccination

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

# data[].attributes.abstract
Since 2020, over 600 million COVID-19 vaccinations and 500 million influenza vaccinations have been administered in the United States. These vaccines have saved millions of lives by inducing the differentiation and maturation of antigen-specific B cells into antibody-secreting cells, resulting in the generation of high-affinity, protective antibodies. However, little is known about how these antibodies could regulate the ongoing B cell response or subsequent responses to vaccination. Notably, a durable B cell response that produces long-lived antibody-secreting plasma cells and poised memory B cells relies on the processes of affinity maturation and clonal expansion, which occur in anatomical structures called germinal centers (GCs). This proposal aims to provide insight into antibodies' role in regulating germinal center responses. This is a particularly important concept for vaccinations that occur in the context of pre-existing humoral immunity, as in seasonal influenza or COVID-19 booster vaccinations. In Aim 1, the hypothesis of antibody feedback on vaccine-elicited GC B responses will be tested in a newly generated mouse model where IgG1 antibody secretion can be inducibly blocked. The GC response's quality, magnitude, and duration will be characterized in primary and heterologous boost systems. In Aim 2, the same overarching hypothesis will be examined in a human rabies vaccination model. Here, the impact of polyclonal rabies immunoglobulin administration on vaccine-induced GC B cells will be examined for epitope specificity, magnitude, and kinetics changes. Additionally, GC products, long-lived memory B cells, and bone marrow plasma cells will be characterized in the presence and absence of exogenous antibodies. The overall goal of this proposal is to test hypotheses of antibody feedback on GC B cells in complementary systems that combine unique mechanistic probing in mice with authentic human vaccine responses. These findings will have broad public health implications for the millions of vaccinations administered yearly in the United States. During the fellowship, the applicant will acquire fundamental skills that will serve as a steppingstone toward becoming an independent investigator in vaccine research. This will include developing expertise in both rodent and human vaccination models. As described in the proposed training plan, the applicant will be supported by Drs. Ellebedy and Diamond who have demonstrated experience in B cell vaccine responses and mentorship of scientific trainees. With Washington University's track record of excellence in training immunologists and physician-scientists, the applicant will be well-equipped for success in their training towards becoming a physician-scientist.

# data[].attributes.keywords[]
Structure of germinal center of lymph node

# data[].attributes.title
TEAM-UP: Tobacco treatment navigators uniting with primary care

# data[].attributes.abstract
Tobacco use disorder is the deadliest substance use disorder accounting for nearly half a million premature deaths in the United States each year. Primary care clinics have the potential to reach the majority of the population with tobacco cessation assistance in the context of ongoing care, but uptake of evidence-based strategies is poor. Team-based and electronic health record-supported approaches to promote tobacco assessment and referral to cessation services (e.g. Quitlines) have been successful, but were significantly disrupted by the sequelae of COVID-19. Population outreach approaches using navigators and technologies such as patient portals have been effective in facilitating patient access to and engagement with care services and can improve health outcomes. Important gaps in understanding which outreach approaches effectively reach and engage low-income primary care patients with tobacco cessation support remain. We propose that using an outreach strategy focused on patients who were not assisted during a recent primary care visit will greatly improve the delivery of tobacco cessation support to patients. We examine two outreach strategies: a predominately person-based outreach navigator (ON) vs. a technology-based interactive patient portal (IPP). Patients that are not offered assistance during a primary care visit will be randomized into 3 groups: ON vs. IPP vs. usual care / no outreach group (NOC). Both implementation strategies will use an evidence-based approach to communicate the importance of cessation counseling and tobacco cessation medications for an effective quit strategy, offer patient choice among options, and facilitate referrals to tobacco cessation counseling and orders for medications using EHR tools. This study aims to: 1. Implement a tobacco treatment outreach intervention with ON vs. IPP vs. NOC to compare rates and  correlates of receipt of cessation counseling and tobacco cessation medication orders. 2. Evaluate the effectiveness of ON vs. IPP vs. NOC on tobacco quit status. 3. Estimate and compare the costs and cost-effectiveness of ON vs. IPP. These aims will be accomplished with a three-arm randomized trial with 6000 patients (randomization ratio of 1:1:1) from 10 community-based clinics. EHR data and patient surveys will be used to assess the effect of the ON vs. IPP vs. NOC on patient reach and effectiveness outcomes and whether the approaches work equitably across important subgroups of patients. We will also assess the cost to implement and conduct each outreach approach and conduct cost-effectiveness analyses. For each Aim, qualitative methods will complement the hypothesis testing analyses to better inform observed differences in outcomes of the approaches. This study is well aligned with NIDA priorities and fills a critical knowledge gap of identifying effective and scalable strategies to improve tobacco cessation assistance among low-income primary care patients.

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Dissemination of the Education in Palliative and End-of-life Care–Pediatrics (EPEC-Pediatrics) Train-the-Trainer Curriculum: Phase 2

# data[].attributes.abstract
Most children living with advanced cancer experience highly distressing symptoms, and many do not have access to subspecialist pediatric palliative care (PPC) services or clinicians trained in primary palliative care. Despite the call from national organizations for the integration of palliative care for patients with cancer, a lack of high-quality PPC education persists as a barrier to PPC implementation. From 2012-2017 the investigators of the current proposal developed and disseminated the most comprehensive PPC curriculum worldwide to date: Education in Palliative and End-of-Life Care (EPEC)-Pediatrics (NIH/NCI grant #R25 CA151000-01). The 24-module curriculum is designed to teach clinicians how to teach and advance PPC concepts. The primary target audience was pediatric oncology prescribing clinicians. The curriculum is delivered through combined online learning and face-to-face conferences. When the COVID-19 pandemic emerged, an online training platform was created, enabling remote worldwide participation. Forty conferences have been held to date, training 1,992 clinicians from 122 countries. Most participants have reported improvement in PPC knowledge, attitudes, and skills, and advancements in patient care for children with cancer and serious illnesses. Further dissemination has been achieved through five publications and dozens of academic presentations. The primary goal of this project is to improve EPEC-Pediatrics accessibility and inclusivity by targeting participants from US pediatric oncology programs outside of large tertiary centers, including non-prescribing interprofessional clinicians (e.g. social workers). The project will also address disparities in PPC education by adding faculty from underrepresented communities, such as infants. Further, the curriculum will be updated to ensure content is current and inclusive, reflecting the needs of all children with cancer and families, including those with special needs. Specific aims are to: 1) Disseminate the EPEC-Pediatrics curriculum through five annual EPEC-Pediatrics Train-the-Trainer conferences in previously geographically underrepresented areas of the US (e.g., Southern region). 2) Update and expand the existing EPEC-Pediatrics curriculum and dissemination project by: a) Seeking guidance from an interprofessional group of clinical experts (e.g., bereaved parents) to improve curriculum content and ensure it includes equitable and inclusive content; b) Strengthening the psychosocial-spiritual curriculum content through emphasis of care for special populations (e.g., infants with cancer); and c) Designing a learning pathway for non-prescribing clinicians. Successful adaptation and dissemination of a more holistic EPEC-Pediatrics curriculum will promote transfer of PPC best practices to underserved communities, ultimately changing clinician behavior and improving care for children with cancer and their families.

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United States National Institutes of Health

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2025 Liquid Crystals Gordon Research Conference and Gordon Research Seminar

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National Institute of Biomedical Imaging and Bioengineering (NIBIB)

# data[].attributes.abstract
Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. SUMMARY Significance, timeliness and rationale. NIBIB’s mission is to transform through engineering the understanding of disease and its prevention, detection, diagnosis, and treatment. Life would not be possible without liquid crystalline (LC) order. The most celebrated example is the unique combination of flexibility and confining ability of cell membranes which is possible because lipids cooperatively aggregate into a lamellar LC phase in water. Many viruses, e.g., SARS-CoV-2, are enveloped in a lipid membrane and they may employ LC order for packing their nucleic acid cargo. Non-biological LCs have turned out to be sensitive in detecting and reporting on the presence of pathogens and toxins, making them highly interesting for autonomous bio-/chemosensors. LC formation is thus an integral component of what keeps us healthy, and they are emerging as a powerful tool for detecting disease agents. Although this connection is long known, it has until now been researched only marginally, constituting an under-explored opportunity in addressing societal needs. Today, the international LC research community is undergoing a rebirth, fully embracing these aspects. Interdisciplinary crossovers where LC science meets biological, life and pharmaceutical sciences, and engineering and materials science, play a groundbreaking role in leveraging the opportunities. Additional impact on the core fields of the NIH-NIBIB mission comes from, e.g., the exploration of LC elastomers in soft actuators or implants in the human body. Objective. Gordon Research Conference (GRC) and Gordon Research Seminar (GRS) in Liquid Crystals, 2025: “Uniting disciplines for global challenges: Liquid crystals as active and learning materials” to take place July 6-11th 2025 (GRS July 5-6, 2025) at the Southern New Hampshire University, Manchester, NH, US. The joint meetings will bring together US and international researchers at the forefront of today’s vibrant LC science, spanning its full breadth and connecting academia, industry and military labs, early career and established researchers, and harnessing every opportunity to promote scientific discussions and encourage collaboration between speakers, discussing leaders and participants. Approach. 23 prominent speakers have confirmed our invitations to present unpublished cutting-edge research. Our goal is to promote the participation of students, postdocs, and scholars at an early stage of their careers. We seek to promote scientific discussion among all participants who will fuel the future of Liquid Crystal Science in biomedical and biotechnology applications. Academic speakers are complemented by 2 industry and 2 military research lab speakers. Additionally, 5 speaker slots will be given to outstanding scientists selected from submitted poster abstracts. To further strengthen the voice of young researchers, the GRC is preceded by the GRS, catering only to students and post-docs and providing mentoring and career advice. During the GRC, young scientists will be given priority in all scientific discussions.

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National Institute of Biomedical Imaging and Bioengineering

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United States National Institutes of Health