Medicine and Health Sciences Commons^™

Brief Report: Hepatitis B Vaccination Histories In Persons With Hiv Needing Revaccination, Minhee Kang, Triin Umbleja, Anchalee Avihingsanon, Sandra W Cardoso, Josphat Kosgei, Karen J Vigil, Ta Thi Dieu Ngan, Unoda Chakalisa, Stephanie Caruso, Kenneth E Sherman, Kristen M Marks

Faculty, Staff and Student Publications

Introduction: Past studies of hepatitis B vaccines in people with HIV (PWH) have shown mixed results about improving responses with increases in dose or dose frequency, leading to inconsistent guidelines and practice. We examined vaccine series completion and revaccinations in PWH lacking a seroprotective response.

Methods: Hepatitis B vaccination histories were evaluated as a retrospective study in 561 participants of A5379 trial (NCT04193189). Individuals in 41 sites in Africa, Asia, South America, and the United States qualified for the trial with antibody titers below the seroprotective level (< 10 mIU/mL) despite past hepatitis B vaccinations. The primary measure of interest was the number of vaccines in the past vaccination records.

Results: Of the 1098 trial candidates, 561 (51%) did not …

Quantitative Muscle Magnetic Resonance Imaging Demonstrates Resolution Of Muscle Edema In Refractory Dermatomyositis: A Post Hoc Analysis Of A Proof-Of-Concept Clinical Trial Of Tofacitinib, Mona Dabiri, Anshula Nallapati, Marwin Groener, Patrick Debs, Jemima Albayda, Eleni Tiniakou, Lisa Christopher-Stine, Laura Fayad, Julie J Paik

Faculty, Staff and Student Publications

Objective: To evaluate changes in muscle edema using short-tau inversion recovery (STIR) imaging and quantitative diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping in patients with refractory dermatomyositis (DM) treated with tofacitinib.

Methods: This post hoc imaging analysis included patients from a 12-week, open-label trial of tofacitinib 11 mg daily in refractory DM. Bilateral thigh magnetic resonance imaging was obtained at baseline and week 12 using standardized STIR, T1-weighted, and DWI sequences. Muscle edema (ME) and fascial edema were assessed qualitatively on STIR imaging. ADC values were measured in muscles demonstrating baseline STIR hyperintensity using three nonoverlapping regions of …

Race To Mitigate Aortic Dissection: Exercise, Pde5a, And The Dissecting Aorta, Siddharth K Prakash

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Rapid Infusers On The Hemostatic Potential Of Cryoprecipitate Products, Connor D Purvis, Samantha Redden, Andrew Jacobson, Yao-Wei Wang, Julie Campbell, Jessica Cardenas, Jan-Michael Van Gent, Bryan A Cotton

Faculty, Staff and Student Publications

Background: In cases of massive transfusion, intravenous access can be limited. Additionally, delivering different products through separate lines and infusion methods adds unnecessary steps. RBC, plasma, and whole blood (WB) are delivered via rapid infusers; cryoprecipitate (CRYO) is infused through separate access and is not approved with these devices.

Study design and methods: We examined the impact of different transfusion methods on hemostatic performance and factor activity using two available CRYO products. Ten bags of CRYO, ten bags pathogen-reduced CRYO (Intercept® Fibrinogen Complex, IFC), and 20 units of WB were obtained. Each CRYO bag was infused with one unit of …

Estrogen As A Therapeutic Agent: Targeting Endotheliopathy And Coagulopathy In Trauma, Niruktha Raghavan, Mira Patel, Bryan A Cotton, Julia Coleman, Donald Jenkins

Faculty, Staff and Student Publications

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products …

Declaring Futility After Traumatic Injury And The Burden Of Failure On The Surgeon, Jan-Michael Van Gent, Bryan A Cotton

Faculty, Staff and Student Publications

In this edition of the THOR supplement in Transfusion, there are two articles that deal with resuscitation futility and transfusion. In one article, Yazer et al. delve into the details of the studies outlined in this editorial and summarize the literature on the topic of transfusion and futility. The second article by Dr. Jay Malone discusses the ethical issues surrounding massive transfusion and resuscitation. Taken together, these articles address the clinical and ethical issues surrounding this very emotive and difficult topic.

Risk-Stratified Transitional Care And Cardiovascular Hospitalizations By Sex: A Secondary Analysis Of A Randomized Clinical Trial., Douglas S Lee, Chang Nancy Wang, Peter C Austin, Sharon E Straus, Michael E Farkouh, Alice Chong, Monica Taljaard, Stephanie Poon, Stuart Smith, Robert S Mckelvie, Robert M Iwanochko, Andrea Macdougall, Esam Elbarasi, Peter M Cram, Jiming Fang, Clare L Atzema, Jacob A Udell, Paula A Rochon, Michael J Schull, Susanna Mak, Heather J Ross

Heart and Vascular Articles

IMPORTANCE: Female patients with heart failure (HF) are older and more often present with preserved left ventricular ejection fraction (LVEF), whereas male patients present with more ischemic disease. Despite these differences, an emergency department-based acute HF strategy may be equally applicable to both sexes.

OBJECTIVE: To determine whether the strategy for acute HF management in the Comparison of Outcomes and Access to Care for Heart Failure (COACH) trial differed by sex.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the multicenter COACH stepped-wedge, cluster-randomized clinical trial included 10 acute care hospitals in Ontario, Canada. Data were collected from January …

Rethinking Mixed Dka-Hhs: An Extreme Presentation Of Hyperosmolar Hyperglycemic State, Sajith Silva, Umair Malik, Amin Pasha, Sujata Kambhatla

Conference Presentation Abstracts

Introduction: The American Diabetes Association (ADA) recognizes diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) as life-threatening hyperglycemic emergencies that can overlap clinically; approximately 10% of presentations are described as mixed DKA–HHS. Because current guidelines do not define a single “mixed” category, overlap is best understood as concurrent fulfillment of key elements of both syndromes: DKA-type anion-gap metabolic acidosis with ketonemia or ketonuria, together with HHS-type severe hyperglycemia, hyperosmolality, and dehydration. We report an extreme HHS presentation (glucose >2,100 mg/dL) with limited DKA overlap. Case Description: A 34-year-old woman with longstanding type 1 diabetes mellitus managed with an insulin pump, …

A Rare Price Of Pain Control: Methemoglobinemia From A Lidocaine Patch, Sushmita Mantravadi, Kesava Mankikanta Achuta, Aaron Goyal, Amin Pasha, Abed L. Dabaja

Conference Presentation Abstracts

Introduction The overall prevalence of methemoglobinemia is around 0.035%. Methemoglobinemia is a rare but potentially life-threatening complication of local anesthetic use. While all patients are at risk, those with cardiac or pulmonary compromise are more susceptible to developing clinical manifestations. We report a case of acquired methemoglobinemia following topical lidocaine patch application for post-operative pain management in an elderly patient. Case Presentation 84-year-old male with a past medical history of aortic stenosis status post Transcatheter aortic valve replacement, Coronary artery disease, gastrointestinal bleed due to colon polyps, obstructive sleep apnea, chronic kidney disease, trigeminal neuralgia, obesity, essential hypertension, chronic atrial …

Neurointerventional Advances In 2025, Amol Mehta, Sunil A Sheth, Ashutosh P Jadhav

Faculty, Staff and Student Publications

No abstract provided.

Antidepressant-Like Effects Of Extinction Learning As An Animal Model Of Behavioral Therapy, Jing Liu, Sarah E Bulin, David A Morilak

Faculty, Staff and Student Publications

Exposure-based behavioral therapy, the most effective treatment for posttraumatic stress disorder (PTSD), also reduces depressive symptoms. However, neurobiological mechanisms underlying the beneficial effects of exposure-based behavioral therapy on depression remain unknown. Our lab has established fear extinction as a rat model of exposure therapy to investigate the mechanisms underlying its therapeutic behavioral effects in chronically stressed rats. In this study, we demonstrated that extinction learning reduced immobility in the forced-swim test and reversed chronic stress-induced reduction in sucrose preference. Chemogenetic inactivation of pyramidal neurons in the ventral medial prefrontal cortex (vmPFC) prevented these antidepressant-like effects of extinction. Extinction learning enhanced …

Creating Space For New Ideas And Advancing Gender Equity In Physical Activity And Health Research: Reflections On The Nature Portfolio Physical Activity Series, Andrea Ramírez Varela, Deborah Salvo, Pedro C Hallal, Erica Hinckson

Faculty, Staff and Student Publications

No abstract provided.

Computational Modeling Meets 3d Bioprinting: Emerging Synergies In Cardiovascular Disease Modeling, Tanmay Mukherjee, Mehdi Salar Amoli, Sarah Rezapourdamanab, Lama Rita El Shammas, Martin L Tomov, Emilio A Mendiola, Vahid Serpooshan, Reza Avazmohammadi

Faculty, Staff and Student Publications

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, underscoring the need for improved strategies in diagnosis, treatment, and disease modeling. Traditional in vitro models often fall short in replicating human CV physiology, prompting efforts to advance cardiac tissue engineering and computational modeling. Among these, three-dimensional (3D) bioprinting has emerged as a transformative tool, enabling the creation of biomimetic CV constructs that more faithfully replicate native tissue structure and function. However, challenges persist in achieving appropriate mechanical properties and long-term performance of engineered CV constructs. Computational modeling offers powerful solutions to assist with these challenges, providing predictive insights into …

Are Drains After Trauma Splenectomy Associated With Organ Space Surgical Site Infections?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Seokhun Kim, William D Rieger, Renee W Green, Gabrielle E Hatton, Lillian S Kao

Faculty, Staff and Student Publications

Introduction: Left upper quadrant (LUQ) drain use after trauma splenectomy varies, with minimal existing data to guide practice. We aimed to investigate the association of LUQ drains with organ space surgical site infection (OS-SSI) after splenectomy. We hypothesized that LUQ drains after trauma splenectomy are associated with increased odds of OS-SSI.

Patients and methods: A retrospective study of adult blunt trauma patients who underwent splenectomy from 7/2018 to 6/2024 was performed. We excluded patients who survived < 5 days after operation, and those with an intraoperatively identified pancreatic injury. Demographics, surgical details, and drain information were abstracted from the medical record. Inverse probability of treatment weighting (IPTW) was used to balance variables between patients who did and did not receive an LUQ drain after splenectomy. Multivariable logistic regression with IPTW was performed to estimate the association of LUQ drains with OS-SSI.

Results: Of 179 patients, 68% (n = 121) were male, the median age was 38 years (interquartile range 28, 55), and 27% (n = …

An Assessment Of Green Plasma: The In Vitro Hemostatic Superiority Of A Currently Discarded Blood Product, Samantha C Redden, David J Sun, Yao-Wei W Wang, Elizabeth Hartwell, Jessica C Cardenas, Scott D Olson, Bryan A Cotton

Faculty, Staff and Student Publications

Introduction: Recent studies have linked trauma patient outcomes to the plasma donor's sex, with premenopausal females associated with improved survival and lower organ failure. Currently, green-colored plasma (due to oral contraceptive use) is removed from the donor pool. We set out to evaluate the hemostatic potential of green plasma.

Study design & methods: We obtained 90 units of plasma from our regional blood center: 30 units of visible green plasma and 60 units of standard-color plasma divided between male and female donors. We collected clinical data such as age, sex, ethnicity, and number of pregnancies. We then assessed the hemostatic …

Associations Between Source-Specific Nitrate And Nitrite Intakes And Metabolic Dysfunction-Associated Steatotic Liver Disease In Two Prospective Cohorts, Nicola P. Bondonno, Pratik Pokharel, Benjamin H. Parmenter, Liezhou Zhong, Dorit W. Erichsen, Jörg Schullehner, Kirsten Frederiksen, Cecilie Kyrø, Peter Fjeldstad Hendriksen, Jonathan M. Hodgson, Torben Sigsgaard, Christina C. Dahm, Anne Tjønneland, Alysha S. Thompson, Tilman Kühn, Aedín Cassidy, Anja Olsen, Catherine P. Bondonno

Research outputs 2022 to 2026

SummaryBackground and AimsDietary nitrate and nitrite may have source-dependent effects on liver health: plant-sourced nitrate may confer hepatoprotective benefits via its conversion to nitric oxide, whereas nitrate and nitrite from animal foods, processed meats, or contaminated drinking water may promote liver injury via their conversion to N-nitrosamines. We aimed to examine associations between source-specific nitrate and nitrite intakes and incident metabolic dysfunction-associated steatotic liver disease (MASLD) in two large cohorts. Secondary aims were to assess associations with liver MRI biomarkers and to evaluate whether nitric oxide-pathway gene variants modify associations with plant-sourced nitrate/nitrite.MethodsWe analysed 53,854 participants from the Danish Diet, …

Beyond The First Bout: Adaptations To Repeated Injuries Across Physiological And Pathological Conditions, Cory W. Baumann, Christopher P. Ingalls, Kazunori Nosaka, Jarrod A. Call

Research outputs 2022 to 2026

Skeletal muscle exhibits remarkable plasticity following injury, yet most research has focused on responses to a single bout of eccentric contractions. This review addresses adaptations to repeated eccentric contraction–induced injuries across physiological and pathological conditions, with emphasis on insights from preclinical rodent models. In healthy muscle, the repeated bout effect (RBE) reduces strength loss and accelerates recovery after subsequent bouts. However, these adaptations are highly condition dependent. Aging can attenuate the RBE, while dystrophic muscle remains vulnerable to repeated injury despite compensatory remodeling. Other factors, including but not limited to, chronic alcohol intake and malignant hyperthermia can influence these responses, …

Digital Decoding Of The Multidimensional Pain Experience In People Living With Dementia, Kreshnik Hoti, Ipsit V. Vahia, Paola Chivers, Jeffery David Hughes

Research outputs 2022 to 2026

Background: Understanding how pain manifests in people living with dementia can facilitate pain management but evidence from large real-world studies is limited. Through digitally compiled large number of pain assessments, we explore how behavioural indicators manifest across all widely used domains of pain assessment. Methods: This is a population based observational study with data from aged care homes across Australia, New Zealand and the United Kingdom. Pain assessments were conducted over a period of 5.3 years in 89 230 residents living with advanced dementia. The primary outcome was to determine pain indicator occurrence across pain levels and explore their predictive …

Transitioning To Adolescent And Young Adult Or Adult Cancer Survivorship Care: A Systematic Review Of Contemporary Guidelines And Trials, Darren Haywood, Hammersley, Ursula Sansom-Daly, Jordana Mcloone, Evan Dauer, Helen Wilding, Nicolas H. Hart, Thomas Walwyn

Research outputs 2022 to 2026

Background: Health service transitions of child, adolescent, and young adult cancer survivors between paediatric and adult cancer care services are pervasively fragmented, resulting in poor coordination, reduced satisfaction, and adverse outcomes for cancer survivors and significant others (e.g., caregivers and family members). Numerous trials and clinical guidelines have been developed to support care transitions, but their convergence, divergence, and methodological quality remain unclear. To advance clinical practice and quality research about care transitions, a synthesis of trials and guidelines on child, adolescent, and young adult care transition across age-appropriate cancer services is required to inform future research, practice, guideline, and …

Diacylglycerol Kinase Eta As A Novel Target In Nras Mutant Melanoma, Haley P. Wilson, Casey D. Stefanski, Signe Caksa, Glenn L. Mersky, Scott D. Varney, Jelan I. Haj, Dan A. Erkes, Timothy J. Purwin, Vivian Chua, Andrew E. Aplin

Research outputs 2022 to 2026

NRAS mutations occur in 10%–30% of cutaneous melanomas and are associated with high tumor mutational burden. Mutant NRAS signaling drives aberrant cell growth and proliferation, in part, through activation of the RAF–MEK-ERK1/2 kinase pathway; however, targeted therapies to this pathway have limited effectiveness in patients with NRAS mutant melanoma. The role of other targetable signaling pathways in NRAS mutant melanoma is poorly characterized. Here, we demonstrated that one isoform of diacylglycerol kinase, diacylglycerol kinase eta (DGKη), a lipid signaling regulator, was highly expressed in NRAS mutant melanoma patient samples. Knockdown of DGKH in NRAS mutant melanoma cell lines resulted in …

Circulating Sphingomyelins Correlate With Plasma T-Tau In Cognitively Unimpaired Older Adults At Risk Of Developing Alzheimer's Disease, Tahmida Sharmin, James D. Doecke, Pratishtha Chatterjee, Steve Pedrini, Hamid R. Sohrabi, Nicholas J. Ashton, Henrik Zetterberg, Manohar L. Garg, Kaj Blennow, Ralph N. Martins

Research outputs 2022 to 2026

Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total-tau (T-tau) remain valuable in indicating AD-related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non-invasive detection and treatment approaches. This cross-sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid-β (Aβ) status through positron …

A High-Throughput Assay For Monitoring And Quantifying Amyloid-Β Accumulation And Clearance In Alzheimer's Disease Cell Models, Ajish Ariyath, Fraulein Denise Arigo, Anna Fyfe, W. M.A.D.Binosha Fernando, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Amyloidogenic proteins, such as amyloid-β (Aβ), self-assemble into cross-β fibrils whose accumulation is central to Alzheimer's disease (AD). Measuring Aβ aggregation and clearance in living cells remains challenging using current cell-based assays, which are often low-throughput or not suited for real-time monitoring. This study aimed to (1) develop a robust, quantitative, and scalable fluorescence-based assay using Amytracker to monitor Aβ accumulation and clearance in an Aβ-producing neuronal cell model, and (2) validate its utility for mechanistic studies and therapeutic screening. We established a plate-based fluorescence assay using Amytracker in MC65 neuronal AD model expressing the Amyloid precursor protein C-terminal fragment …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …

Racial, Ethnic, And Neighborhood Disparities In Acute Kidney Injury In Pediatric Acute Leukemia, Wendy C Bravo, Yimei Li, Tamara P Miller, Kelly Getz, Lusha Cao, Edward Krause, Mark Ramos, Judy Lee, Maria Monica Gramatges, Karen R Rabin, Michael Scheurer, Richard Aplenc, Michelle Denburg

Faculty, Staff and Students Publications

Introduction: We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML).

Methods: Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first …

Interplay Between Genetic Ancestry, Self-Reported Race And Ethnicity, And Clinical Factors In Pediatric Acute Lymphoblastic Leukemia: A Redial Consortium Report, Pragati Kore, Jennifer M Geris, Maria Leon-Camarena, Maria I Castellanos, Olga A Taylor, Veronica Garcia-Morales, Austin L Brown, Pagna Sok, Jeremy M Schraw, Van Huynh, Kathleen F Ludwig, Laura J Klesse, Sandi L Pruitt, Amy E Hughes, Kevin Tien, Kenneth M Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Maria M Gramatges, Elizabeth G Atkinson, Philip J Lupo, Michael E Scheurer, Karen R Rabin

Faculty, Staff and Students Publications

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children, and its incidence and outcomes vary by race and ethnicity.

Methods: The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium has assembled a cohort of patients < 25 years at diagnosis to examine genetic and neighborhood-level factors influencing ALL. As the cohort is ongoing, for this report, we examined sociodemographic and cytogenetic factors that might be associated with ALL outcome disparities.

Results: Among 2,512 patients diagnosed between 2005 and 2020, we observed distinct patterns of genetic ancestry and residential characteristics across self-reported race and ethnicity. Latino children, who comprised 55.3% of the cohort, had a mean Amerindigenous ancestry proportion of 50.9%, whereas non-Latino White children exhibited a predominantly European ancestry (mean = 78%). Neighborhood-level analysis revealed significant socioeconomic and geographic differences by …

Maternal Fish Intake In The Year Prior To Conception And Birth Defects, National Birth Defects Prevention Study, 1997-2011, Dorothy Kim Waller, Zeyu Miao, Renata H Benjamin, Richard Finnell, Nithya Lakshmi Mohan Dass, Eirini Nestoridi, Marcia C De Oliveira Otto, Julie Peterson, Tunu Ramadhani, Mark A Canfield

Faculty, Staff and Students Publications

Background: Epidemiologic data on the association between maternal fish intake and birth defects are sparse. Our objective was to assess associations between maternal fish intake and 52 different birth defects, most of which have not been assessed previously.

Methods: Using logistic regression, data was analyzed for 29,242 mothers of infants with birth defects and 10,973 mothers of control infants who participated in the National Birth Defects Prevention Study (NBDPS) and delivered between 1997 and 2011. We focused on associations between mothers who reported high fish intake of 2 or more servings of fish per week for the year prior to …

A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al.

2020-Current year OA Pubs

UNLABELLED: The NRF2 transcription factor is constitutively active in cancer, in which it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2 dependency and resistance to chemotherapy/radiotherapy (RT). In this study, we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the Kelch-like ECH-associated protein 1 (KEAP1)-cullin3 (CUL3) ubiquitin-ligase complex. VVD-065 specifically and covalently engages Cys151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported Cys151-directed compounds decrease KEAP1-CUL3 interactions …

Computational Fluid Dynamics-Based Risk Stratification Of Modified Blalock-Taussig-Thomas Shunt Thrombogenicity, Yi Qiao, Ethan Penn, Jacob Miller, Scott Bugenhagen, Ram Rohatgi, Kelsey Mercer, Blaire Kulp, Jinli Wang, Pirooz Eghtesady, Guy M Genin, Edon J Rabinowitz, David Bark

2020-Current year OA Pubs

BACKGROUND: The modified Blalock-Taussig-Thomas shunt (mBTTS) is a critical palliative procedure for infants with single-ventricle physiology, but thrombosis-related occlusion affects 8% to 12% of infants and carries nearly 50% mortality. Meanwhile, existing antithrombotic strategies fail to address the hemodynamic factors driving thrombosis, highlighting the need for a deeper understanding of flow dynamics in shunt failure.

OBJECTIVES: This study aims to identify how mBTTS geometry influences hemodynamics and thrombosis risk, providing quantitative guidance for surgical planning and shunt design optimization.

METHODS: We used patient-specific imaging data to test 54 idealized mBTTS configurations, systematically varying key geometric factors: pulmonary artery diameter, shunt …

Plasma Proteins Associated With Psychosocial Factors And Heart Disease: The Jackson Heart Study, Sara N O'Brien, Madeline G Gillman, Michael D Green, Daniel E Cruz, James S Floyd, Susan Hankinson, Daniel H Katz, Xiaojuan Liu, Michelle C Odden, Bruce M Psaty, Alexander P Reiner, Jerome I Rotter, Stephen S Rich, Robert E Gerszten, Amil Shah, Mario Sims, Usman A Tahir, Lesley F Tinker, Alexis C Wood, Bing Yu, Anthony S Zannas, Laura M Raffield, Láshauntá M Glover

Faculty, Staff and Students Publications

Background: Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

Methods: JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies …

Ixodid And Flea Infestations And Associated Bacteria On Two Sympatric Felid Species In South Texas, Allan T Showler, Hilary Swarts, Maya Murry, Alisa Nelson, Alexander R Kneubehl, Sarah M Gunter

Faculty, Staff and Students Publications

Ixodid ticks and fleas parasitize wild felids and can transmit pathogens of veterinary and public health concern. We identified ixodid and flea species collected from sympatric South Texas bobcats, L. rufus, and ocelots, L. pardalis. Greater diversities of ixodids were found on both felids than in previous reports, with seven species in three genera on L. rufus and six species in three genera on L. pardalis. We report first findings of tropical horse tick, Dermacentor nitens, on L. rufus in Texas, and Ixodes keiransi on both felids in Texas. Although false cayenne tick, Amblyomma tenellum, nymphs were the most abundant …