Digital Commons Network^™

Structural And Functional Diversity Of Type Iv Secretion Systems, Melissa R Cruz, Shane Cristy, Shantanu Guha, Giuseppe Buda De Cesare, Elena Evdokimova, Hiram Sanchez, Dominika Borek, Pedro Miramón, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …

Measurement Of Severe Acute Respiratory Syndrome Coronavirus 2 Antigens In Plasma Of Pediatric Patients With Acute Coronavirus Disease 2019 Or Multisystem Inflammatory Syndrome In Children Using An Ultrasensitive And Quantitative Immunoassay, George B Sigal, Tanya Novak, Anu Mathew, Janet Chou, Yubo Zhang, Navaratnam Manjula, Pradeepthi Bathala, Jessica Joe, Nikhil Padmanabhan, Daniel Romero, Gabriella Allegri-Machado, Jill Joerger, Laura L Loftis, Stephanie P Schwartz, Tracie C Walker, Julie C Fitzgerald, Keiko M Tarquinio, Matt S Zinter, Jennifer E Schuster, Natasha B Halasa, Melissa L Cullimore, Aline B Maddux, Mary A Staat, Katherine Irby, Heidi R Flori, Bria M Coates, Hillary Crandall, Shira J Gertz, Adrienne G Randolph, Nira R Pollock, Overcoming Covid-19 Investigators

Center for Medical Ethics and Health Policy Staff Publications

Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery).

Methods: Plasma was collected from inpatients (< 21 years) enrolled across 15 hospitals in 15 US states. Acute COVID-19 patients (n = 36) had a range of disease severity and positive nasopharyngeal SARS-CoV-2 RT-PCR within 24 hours of blood collection. Patients with MIS-C (n = 53) met CDC criteria and tested positive for SARS-CoV-2 (RT-PCR or serology). Controls were patients pre-COVID-19 (n = 67) or within 24 hours of negative RT-PCR (n = 43).

Results: Specificities of N and S assays were 95-97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays …

The Temporal Impulse Response Function In Infantile Nystagmus, Gal Avital, Felicia Kuperwaser, Andrew W Pountain, Keenan A Lacey, Erin E Zwack, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Itai Yanai

Faculty, Staff and Student Publications

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at …

Collaborative Quality Improvement Strategy In Secondary Prevention Of Cardiovascular Disease In India: Findings From A Multi-Stakeholder, Qualitative Study Using Consolidated Framework For Implementation Research (Cfir), Kavita Singh, Mark D. Huffman, Leslie C M Johnson, Nikhil Tandon, Dorairaj Prabhakaran, Emily Mendenhall

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care.

OBJECTIVE: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India.

METHODS: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to …

Preliminary Incidence And Trends Of Infections Caused By Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016-2021, Jennifer P. Collins, Hazel J. Shah, Daniel Lowell Weller, Logan Ray, Kirk Smith, Suzanne Mcguire, Rosalie T. Trevejo, Rachel H. Jervis, Duc J. Vugia, Tamara Rissman, Katie N. Garman, Sarah Lathrop, Bethany Laclair, Michelle M. Boyle, Stic Harris, Joanna Zablotsky Kufel, Robert V. Tauxe, Beau B. Bruce, Erica Billig Rose, Patricia M. Griffin, Daniel C. Payne

Pathology Research and Scholarship

To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts active population-based surveillance for laboratory-diagnosed infections caused by Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia at 10 U.S. sites. This report summarizes preliminary 2021 data and describes changes in annual incidence compared with the average annual incidence for 2016-2018, the reference period for the U.S. Department of Health and Human Services' (HHS) Healthy People 2030 goals for some pathogens (1). During 2021, the incidence of infections caused by Salmonella decreased, incidence of infections caused …

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Robert J Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

Single-Cell Sequencing Reveals Trajectory Of Tumor-Infiltrating Lymphocyte States In Pancreatic Cancer, Aislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara G Hughes, Alexandre Reuben, Shanshan Bai, Min Hu, Tapsi Kumar, Mark W Hurd, Matthew H G Katz, Ching-Wei D Tzeng, Shubham Pant, Milind Javle, David R Fogelman, Anirban Maitra, Cara L Haymaker, Michael P Kim, Nicholas E Navin, Chantale Bernatchez

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical …

Association Between The Affordable Care Act Medicaid Expansion And Receipt Of Cardiac Resynchronization Therapy By Race And Ethnicity, Hunter Mwansa, Ibrahim Barry, Shannon M Knapp, Sula Mazimba, Elizabeth Calhoun, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Background Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in …

Experiences With Prenatal Care Delivery Reported By Black Patients With Low Income And By Health Care Workers In The Us: A Qualitative Study, Alex Friedman Peahl, Michelle H. Moniz, Michele Heisler, Aalap Doshi, Gwendolyn Daniels, Martina T. Caldwell, Vanessa K. Dalton, Ana De Roo, Mary Byrnes

Emergency Medicine Articles

IMPORTANCE: Black pregnant people with low income face inequities in health care access and outcomes in the US, yet their voices have been largely absent from redesigning prenatal care.

OBJECTIVE: To examine patients' and health care workers' experiences with prenatal care delivery in a largely low-income Black population to inform care innovations to improve care coordination, access, quality, and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: For this qualitative study, human-centered design-informed interviews were conducted at prenatal care clinics with 19 low-income Black patients who were currently pregnant or up to 1 year post partum and 19 health care workers (eg, physicians, …

Family Planning, Fertility, And Career Decisions Among Female Oncologists, Anna Lee, Aleksandra Kuczmarska-Haas, Shraddha M Dalwadi, Erin F Gillespie, Michelle S Ludwig, Emma B Holliday, Fumiko Chino

Faculty, Staff and Student Publications

Importance: Female oncologists often spend their childbearing years in training and establishing careers, with many later experiencing fertility issues when starting a family. Physician fertility and family planning are rarely discussed during training. Attitudes among female oncologists regarding family planning are unknown.

Objectives: To understand barriers to family planning as well as the association of fertility treatment with career decisions and to assess experiences of pregnancy-based discrimination among female oncologists.

Design, setting, and participants: In this survey study, a novel 39-item questionnaire was distributed to US female oncologists from May 7 to June 30, 2020, via email and social media …

Synergistic Associations Of Pnpla3 I148m Variant, Alcohol Intake, And Obesity With Risk Of Cirrhosis, Hepatocellular Carcinoma, And Mortality, Hyun-Seok Kim, Xiangjun Xiao, Jinyoung Byun, Goo Jun, Stacia M Desantis, Han Chen, Aaron P Thrift, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Student Publications

IMPORTANCE: Alcohol drinking and obesity are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), but the risk is not uniform among people with these risk factors. Genetic variants, such as I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, may play an important role in modulating cirrhosis and HCC risk.

OBJECTIVE: to investigate the joint associations of the PNPLA3 I148M variant, alcohol intake, and obesity with the risk of cirrhosis, HCC, and liver disease-related mortality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 414 209 participants enrolled in the UK Biobank study from March 2006 …

Current Communication Practices Between Obstetrics And Gynecology Residency Applicants And Program Directors, Helen Kang Morgan, Abigail Ford Winkel, Karen George, Eric Strand, Erika Banks, Fiona Byrne, David Marzano, Maya M Hammoud

2020-Current year OA Pubs

Importance: In order to equitably improve the residency application process, it is essential to understand the problems we need to address.

Objective: To determine how obstetrics and gynecology (OBGYN) applicants and faculty communicate applicants' interest to residency programs, and how program directors report being influenced by these communications.

Design, Setting, and Participants: This survey study was conducted with email surveys of OBGYN application stakeholders in 2022. Included participants were OBGYN applicants, clerkship directors, and residency program directors in medical education associations' email listservs.

Exposures: Surveys sent by the American Association of Medical Colleges, Association of Professors of Gynecology and Obstetrics, …

Considerations For Partnering With Ryan White Case Managers To Create Equitable Opportunities For People With Hiv To Participate In Research, Elizabeth Lockhart, Deanne Turner, Jerome T. Galea, Stephanie L. Marhefka

Center for Health Policy and Health Services Research Articles

Many research studies focus on recruitment from one or few HIV clinics or internet-engaged populations, but this may result in inequitable representation of people with HIV (PWH), across the rural/urban/suburban continuum. Ryan White Case Managers (RWCM) meet regularly with PWH, potentially positioning them as partners in gathering research-related data from diverse groups of low-income, marginalized, PWH. Yet, data collection in partnership with RWCM, particularly over large geographic areas, has been under-explored. We partnered with RWCM and their organizations throughout Florida to administer a 10-item technology use and willingness survey to clients living with HIV; RWCMs provided process-oriented feedback. Among 382 …

Percentage Of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy Vs Placebo In The Treatment Of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial, Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt, Tara Baron, Alyssa A. Forcehimes, Eugene Laska, Sarah E. Mennenga, Kelley O'Donnell, Lindsey T. Owens, Samantha Podrebarac, John Rotrosen, J Scott Tonigan, Lindsay Worth

Family and Community Medicine Research and Scholarship

IMPORTANCE: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.

OBJECTIVE: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.

DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following …

The Situational Contexts And Subjective Effects Of Co-Use Of Electronic Cigarettes And Alcohol Among College Students: An Ecological Momentary Assessment (Ema) Study, James J Yang, Hsien-Chang Lin, Tzung-Shiang Ou, Zhaoxue Tong, Runze Li, Megan E Piper, Anne Buu

Faculty, Staff and Student Publications

INTRODUCTION: Understanding the co-use of e-cigarettes and alcohol, including the situational contexts and subjective effects associated with co-use in real-time is necessary for validating this behavior and informing intervention. Yet, the sparse literature has built upon retrospective data.

METHODS: This study recruited 686 college students who were currently using e-cigarettes from three campuses in the Midwest and South of U.S in Fall 2019-Fall 2021. An on-line survey was conducted to measure e-cigarette use patterns, GPA, e-cigarette and alcohol dependence symptoms, and respiratory symptoms. A 7-day ecological momentary assessment was used to collect real-time data on e-cigarette and alcohol use, situational …

Rumination As A Mediator Of The Association Between Racial Discrimination And Depression Among Black Youth, Donte L Bernard, Colleen A Halliday, Funlola Are, Devin E Banks, Carla Kmett Danielson

Faculty, Staff and Student Publications

BACKGROUND: Racial discrimination constitutes a significant risk factor for depressive symptoms among Black youth. Rumination, a maladaptive self-regulatory stress response, is a notable pathway by which racial discrimination contributes to depressive symptoms among racial/ethnic minority adults. Yet, examinations of the mechanistic nature of rumination in the context of racial discrimination among racial/ethnic minority youth remain limited. The present study investigated rumination as a mediator of the association between racial discrimination and depressive symptoms among Black youth.

METHODS: Data for the current study were drawn from baseline questionnaire responses of community recruited Black pre-and-early adolescents (N = 158, 53% female, M …

Heterozygous Variants In Myh10 Associated With Neurodevelopmental Disorders And Congenital Anomalies With Evidence For Primary Cilia-Dependent Defects In Hedgehog Signaling, Alexander M Holtz, Rachel Vancoillie, Elizabeth A Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J Guillen Sacoto, Yue Si, Ingrid M Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H Sherr, Kimberly A Aldinger, William B Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A Donald, Emily O'Heir, Shade Moody, Katherine H Kim, Barbara K Burton, Grace Yoon, Miguel Del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L Sell, Patricia L Gordon, Jeremy W Prokop, Amel Karaa, Caleb Bupp, Benjamin A Raby

Faculty, Staff and Student Publications

PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis.

RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a …

Comparison Of Brain Nicotine Uptake From Electronic Cigarettes And Combustible Cigarettes, Yantao Zuo, Alexey G Mukhin, Hannah Berg, Janiece D Morgan, Akiva Mintz, Jed E Rose, Kiran Kumar Solingapuram Sai

Faculty, Staff and Student Publications

Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes’ (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.4) and C-cigs, using 11C-nicotine and positron emission tomography (PET). Participants went through two 15-min head scanning sessions during which they inhaled a single puff of E-cig vapor or C-cig smoke containing 11C-nicotine in a randomized order. A full-body scan was …

Cardio-Onco-Metabolism – Metabolic Vulnerabilities In Cancer And The Heart, Anja Karlstaedt, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

Cancer and cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic remodeling is a hallmark of both cancer and the failing heart. Tumors reprogram metabolism to optimize nutrient utilization and meet increased demands for energy provision, biosynthetic pathways, and proliferation. Shared risk factors for cancer and CVDs suggest intersecting mechanisms for disease pathogenesis and progression. In this review, we aim to highlight the role of metabolic remodeling in cancer and its potential to impair cardiac function. Understanding these mechanisms will help us develop biomarkers, better therapies, and identify patients at risk of developing heart disease after surviving cancer.

First-In-Human Phase 1/1b Study To Evaluate Sitravatinib In Patients With Advanced Solid Tumors, Todd Bauer, Byong Chul Cho, Rebecca Heist, Lyudmila Bazhenova, Theresa Werner, Sanjay Goel, Dong-Wan Kim, Douglas Adkins, Richard D Carvajal, Ajjai Alva, Keith Eaton, Judy Wang, Yong Liu, Xiaohong Yan, Jamie Christensen, Saskia Neuteboom, Richard Chao, Shubham Pant

Faculty, Staff and Student Publications

Sitravatinib (MGCD516), a spectrum-selective receptor tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MERTK) and split kinase family receptors, has demonstrated preclinical anti-tumor activity and modulation of tumor microenvironment. This first-in-human phase 1/1b study included sitravatinib dose exploration and anti-tumor activity evaluation in selected patients with advanced solid tumors. Primary objectives included assessment of safety, pharmacokinetics and clinical activity of sitravatinib. Secondary objectives included identifying doses for further investigation and exploring molecular markers for patient selection. In phase 1, 32 patients received 10-200 mg, while phase 1b dose expansion comprised 161 patients (150 mg n = 99, 120 mg n = …

Handling Informative Premature Treatment Or Study Discontinuation For Assessing Between-Group Differences In A Comparative Oncology Trial, Bo Huang, Ryan Sun, Brian Claggett, Lu Tian, Ethan B Ludmir, Lee-Jen Wei

Faculty, Staff and Student Publications

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.

Targeted Inhibition Of Dna-Pkcs, Atm, Atr, Parp, And Rad51 Modulate Response To X Rays And Protons, Scott J Bright, David B Flint, David K J Martinus, Broderick X Turner, Mandira Manandhar, Mariam Ben Kacem, Conor H Mcfadden, Timothy A Yap, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects. In this study we screened the response to X-ray or proton radiation in cell lines treated with DDR inhibitors (DDRis) targeting ATM, ATR, DNA-PKcs, Rad51, …

A Randomized Controlled Trial Evaluating The Effects Of Social Networking On Chronic Disease Management In Rheumatoid Arthritis, Maria A Lopez-Olivo, Jessica T Foreman, Cheuk Leung, Heather Y Lin, Tiffany Westrich-Robertson, Catherine Hofstetter, Jude K A Des Bordes, Anne Lyddiatt, Amye Leong, Irmgard U Willcockson, Susan K Peterson, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVE: Social networking has been shown to improve health outcomes in certain patient populations. While patients with rheumatoid arthritis (RA) increasingly use social networking to communicate with peers, the effects of these interactions are largely unknown.

METHODS: In a randomized controlled trial, we compared RA patients who participated in a social networking group moderated by peer leaders and who had access to a static website offering RA materials with a control group, who only had access to the website. The primary outcomes were patients' RA knowledge, self-efficacy and empowerment. Secondary outcomes included participation in desired health behaviors, and satisfaction with …

Efficacy And Safety Of A Single Dose Of Casirivimab And Imdevimab For The Prevention Of Covid-19 Over An 8-Month Period: A Randomised, Double-Blind, Placebo-Controlled Trial, Gary A Herman, Meagan P O'Brien, Eduardo Forleo-Neto, Neena Sarkar, Flonza Isa, Peijie Hou, Kuo-Chen Chan, Katharine J Bar, Ruanne V Barnabas, Dan H Barouch, Myron S Cohen, Christopher B Hurt, Dale R Burwen, Mary A Marovich, Bret J Musser, John D Davis, Kenneth C Turner, Adnan Mahmood, Andrea T Hooper, Jennifer D Hamilton, Janie Parrino, Danise Subramaniam, Alina Baum, Christos A Kyratsous, A Thomas Dicioccio, Neil Stahl, Ned Braunstein, George D Yancopoulos, David M Weinreich, Covid-19 Phase 3 Prevention Trial Team

Faculty, Staff and Student Publications

BACKGROUND: There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2-8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings.

METHODS: This was a randomised, …

Influence Of Pregabalin Maintenance On Cannabis Effects And Related Behaviors In Daily Cannabis Users, Joshua A Lile, Joseph L Alcorn, Lon R Hays, Thomas H Kelly, William W Stoops, Michael J Wesley, Philip M Westgate

Faculty, Staff and Student Publications

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; …

Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Alexa M Sassin, Grace J Johnson, Alison N Goulding, Kjersti M Aagaard

Faculty, Staff and Students Publications

As rates of Cesarean delivery and common non-communicable disorders (NCDs), such as obesity, metabolic disease, and atopy/asthma, have concomitantly increased in recent decades, investigators have attempted to discern a causal link. One line of research has led to a hypothesis that Cesarean birth disrupts the presumed normal process of colonization of the neonatal microbiome with vaginal microbes, yielding NCDs later in life. However, a direct link between a disrupted microbiota transfer at time of delivery and acute and/or chronic illness in infants born via Cesarean has not been causally established. Microbiota seeding from maternal vaginal or stool sources has been …

Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …