Digital Commons Network^™

The Treatment Of Obesity In The Context Of The Obesity Paradox In Patients With Heart Failure: A Narrative Review, Pamela L. Alebna, Sarah Martey, Anurag Mehta, Carl J. Lavie, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Purpose of review

While excess adiposity is a known risk factor for incident heart failure ( HF), once the condition is established, observational data suggest that increased body mass index (BMI) may confer a survival advantage. This paradox has emphasized the underlying roles of cardiorespiratory fitness (CRF), and body composition, particularly lean mass (LM), in influencing clinical outcomes.

Recent findings

In this review, we explore the multifaceted nature of the obesity paradox in HF, with a focus on emerging anti-obesity incretin-mimetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. These agents …

Longitudinal Changes In Plasma Biomarkers Of Immune Activation, Neuronal Inflammation And Injury In Persons With Hiv Initiating Art, Merle Henderson, Peter Dutey-Magni, Carolina Herrera, Wolfgang Stöhr, Alejandro Arenas-Pinto, Owen Swann, Amanda Heslegrave, Henrik Zetterberg, John Tregoning, Sarah Fidler, François Raffi, Andrea Calcagno, Ab Babiker, Alan Winston

CONRAD Publications

Background

Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual- or triple-antiretroviral therapy (ART) are sparse.

Methods

Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL-6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir-DF/emtricitabine (triple-ART, n = 119) or raltegravir (dual-ART, n = 119) in NEAT-001/ANRS143. Regression models examined associations of baseline and week-96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7-domains) and treatment arm.

Results

In …

A Year In Review On Tuberculosis And Non-Tuberculous Mycobacteria Disease: A 2026 Update For Clinicians And Scientists, Simone Tunesi, Graham Bothamley, Gunar Günther, Yousra Kherabi, Liga Kuksa, Berit Lange, Christoph Lange, Natalie Lorent, Francesca Saluzzo, Martina Sester, Xenia Emilie Sinding Iversen, Marc Tebruegge, Conor Tweed, Anca Vasiliu, Lorenzo Guglielmetti, Tuberculosis Network European Trials Group (Tbnet)

Faculty, Staff and Students Publications

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, while infections from non-tuberculous mycobacteria (NTM) represent a growing public health threat. In its 20th year of activity, the Tuberculosis Network European Trials group (TBnet; www.tbnet.eu) is one of the leading research networks in Europe. In this review, we summarize the main advances in TB and NTM that occurred in 2025.

Methods: We conducted a non-systematic review of articles published in 2025, with a strong emphasis on research with current or potential impact on clinical practice. We also selected the most impactful papers regarding the management of adult …

Definitions Of Arginine Availability: A Critical Metabolic Marker Of Physiological Processes, Mustafa Tosur, Farook Jahoor, Ashok Balasubramanyam

Faculty, Staff and Students Publications

No abstract provided.

Molecular Heterogeneity Of Hpv-Associated Cancers And Strategies To Overcome Treatment Resistance, Sara Rasouli, Weiyi Gong, Raegan Wood, Danyal Daneshdoust, Anam Khan, Rani Mahyoob, Chongwen Cao, Zihao Yu, Nagireddy Putluri, Gennady Shvets, Haichang Li, Bo Zhao, Xuefeng Liu, Jenny Li

Faculty, Staff and Students Publications

Human papillomavirus (HPV) is a major driver of global cancer incidence, responsible for nearly all cervical cancers and a significant proportion of oropharyngeal, anal, and other anogenital cancers. Despite the availability of effective vaccines, HPV-associated cancers persist due to persistent infection, immune evasion, and the virus's ability to integrate into the host genome, contributing to molecular heterogeneity and therapeutic resistance. Here, we summarize molecular heterogeneity and the emerging combined therapeutic strategies. High-risk HPV types, notably HPV16 and HPV18, initiate carcinogenesis through persistent infection of epithelial basal cells and through the actions of the E6 and E7 oncoproteins, which disrupt the …

Sodium Supplementation Algorithm To Promote Growth In Infants Who Are Preterm: Randomized Clinical Trial, Brianna M Liberio, Gregory M Sokol, Hannah Rakow, Kelly Mosesso, Valerie Hole, William W Wong, Shaji K Chacko, Jeffrey L Segar

Faculty, Staff and Students Publications

Objective: Evaluate the effectiveness of an algorithm using urine sodium (Na) concentration to guide dietary Na supplementation compared with standard care to promote growth in infants who are preterm.

Methods: A randomized trial was conducted in 4 neonatal units in Indianapolis, Indiana, involving infants between 250/7 to 296/7 weeks gestation with birthweight > 500 g. Study arms consisted of standard care or use of algorithm beginning at 14 to 17 days postnatal age. The primary outcomes were somatic growth (weight, length, and head circumference) measured by change in Z-score between aged 2 weeks and 36 weeks postmenstrual age (PMA). Secondary outcomes …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …

Mir-302 Regulates Pancreatic Progenitor Pool And Pancreatic Size, Ziyue Z Yang, Caroline G Snider, Ronald J Parchem

Faculty, Staff and Students Publications

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that mir-302 was highly enriched during the earliest stages of pancreatic development. Loss of mir-302 resulted in reduced pancreatic size …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Immune-Mediated Diarrhea And Colitis With Normal Biochemical, Endoscopic And Histologic Findings: A Retrospective Study, Malek Shatila, Sharada Wali, Carolina Colli Cruz, Kei Takigawa, Andres Caleb Urias Rivera, Kian Abdul-Baki, Tanvi Gupta, Elliot Baerman, Linfeng Lu, Irene Jeong-Ah Lee, Raakhi Menon, Hamza Salim, Andrew Sullivan, Varun Vemulapalli, Cristina Natha, Ayesha Khan, Krishnavathana Varatharajalu, Stephane Champiat, Kerry L Reynolds, Lucy B Kennedy, Katy Tsai, Anusha Shirwaiker Thomas, Yinghong Wang

Faculty, Staff and Students Publications

Background: Immune-mediated diarrhea and colitis (IMDC) due to checkpoint inhibition infrequently presents with normal stool biomarkers and no endoscopic or histologic evidence of inflammation. Little is known about the treatment needs and outcomes of this subset of patients. We aimed to describe this entity and clarify the role of immunosuppressive treatments in its management.

Method: This was a single-center, retrospective study of patients treated with immune checkpoint inhibitors who developed clinical symptoms of IMDC, with no evidence of inflammation based on fecal calprotectin or endoscopic/histologic evaluation, between January 2010 and February 2024.

Results: Of 1151 patients with IMDC, 131 (11.4%) …

A Comparative Analysis Of The Sport Mental Health Assessment Tool (Smhat-1) Between Paediatric And Adult Olympic And Paralympic Athletes, Ashley N Triplett, Travis Anderson, Eric G Post, Jessica Bartley, Jeffrey S Shilt, Eric L Dugan, Amber Donaldson, Jonathan Finnoff, William M Adams

Faculty, Staff and Students Publications

Objective: To determine if paediatric athletes exhibit differences in positive screenings on the Sport Mental Health Assessment Tool (SMHAT-1) compared with adults.

Methods: Team USA Olympic and Paralympic paediatric athletes ≤21 years (n=589; 58.8% female; age=19.5±1.7 years) completed the SMHAT-1 between January 2021 and September 2024. A comparative sample of Team USA adult athletes (n=493, 54.2% female; age=27.3±4.9 years) matched for sex and sport was randomly sampled, and the percentage of athletes with a positive screening on each questionnaire was calculated. χ2 analysis compared the proportion of positive screenings between paediatric and adult samples. Piecewise linear regression assessed the association …

A Strategy To Identify Biliary Atresia Efficiently: A Perspective From A Texas Center, Sanjiv Harpavat, Tebyan A Rabbani, Ashley M Upton, Sridevi Devaraj, Jose A Hernandez, Benjamin L Shneider

Faculty, Staff and Students Publications

Infants with biliary atresia are often diagnosed after 60 days of life because the disease is difficult to detect in its early stages. However, infants treated before 30-45 days of life have the best long-term outcomes. To help accelerate the biliary atresia diagnosis, we have developed a streamlined strategy that involves two sequential tests: (1) direct or conjugated bilirubin measurements and (2) a feeding abdominal ultrasound exam. In this review, the strategy is shared to encourage others to provide feedback as well as to consider incorporating portions into their own clinical workflows.

Esophageal Myotomy And Risk Of Esophageal Cancer And Mortality In Achalasia: Real-World Cohort Study, Fouad Jaber, Mohamad Ali Ibrahim, Mohammed Jaber, Youssef Soliman, Mai A Khalaf, Tara Keihanian, Fares Ayoub, Mohamed O Othman, Salmaan Jawaid

Faculty, Staff and Students Publications

Background and study aims: Achalasia is associated with increased risk of esophageal cancer, particularly squamous cell carcinoma. Although esophageal myotomy improves dysphagia, its impact on cancer risk and mortality remains unclear.

Patients and methods: We conducted a retrospective cohort study using the TriNetX research network, including adults (≥ 18 years) with achalasia confirmed by esophageal manometry. Patients were categorized based on treatment of those undergoing esophageal myotomy (peroral endoscopic myotomy [POEM] or laparoscopic Heller myotomy [LHM]) and those managed without myotomy. Patients with prior esophagectomy or malignancies associated with increased esophageal cancer risk were excluded. The primary outcome was incident …

Findings And Recommendations From The State Of The Art (Sota) Conference On Nursing Research To Improve Veteran Outcomes, Amelia E Schlak, Sarah Krein, Laura A Petersen, David Atkins, Catherine Battaglia, Elizabeth Burkhart, Renee Colsch, Marguerite Daus, Heather Gilmartin, Nipa Kamdar, Melissa Knox, Ann Kutney-Lee, Christine M Olney, Kathryn Rugen, Tracy Weistreich, Sheila Cox Sullivan, On Behalf The Nursing Sota Planning Committee

Faculty, Staff and Students Publications

The Veterans Health Administration (VHA), the largest employer of nurses in the United States, has more than 120,000 nursing personnel providing care to over 9 million Veterans across diverse settings. Despite nursing's central role in delivering and sustaining care, research on strengthening the nursing workforce and optimizing nursing practice has remained underdeveloped in VHA. To address this gap, VHA's Office of Research and Development, in partnership with the Office of Nursing Services, convened a State of the Art (SOTA) conference in November 2023 focused on nursing. The Nursing SOTA brought together nurses, researchers, operational leaders, and other stakeholders to review …

Hypothyroidism Is Associated With Higher Healthcare Utilisation And Higher Need For Blood Transfusion After Primary Total Knee Arthroplasty (Tka) In Patients With Osteoarthritis: A National Inpatient Sample Analysis, Sumanth R Chandrupatla, Kranti C Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

Purpose: To examine the association of hypothyroidism with primary total knee arthroplasty (TKA) outcomes in adults with primary underlying diagnosis of osteoarthritis (OA).

Methods: We identified a prospective cohort of patients in the 2016-2020 national inpatient sample (NIS) that received primary TKA with an underlying diagnosis of OA, identified using International Classification of Diseases, Tenth Revision, Common Modification (ICD-10-CM) and Procedure Coding System (ICD-10-PCS) codes in the primary procedure and diagnosis positions, respectively. We performed multivariable-adjusted regression analyses for healthcare utilisation (length of hospital stay, hospital charges and discharge destination) and clinical outcomes (blood transfusion; prosthetic fracture, dislocation or infection; …

Comparing Rotational Thromboelastometry And Standard Coagulation Assays For Predicting Intraoperative Bleeding In Pediatric Liver Transplantation, Kirby Deshotels, Trung Nguyen, Jun Teruya, Muhammed Umair M Mian, Kelby Fuller, Sanjiv Harpavat, Anna Banc-Husu, Amir Navaei, John Goss, Moreshwar Desai, Arun Saini

Faculty, Staff and Students Publications

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear.

Methods: In this single-center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen-based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …

Dynamic Progression Of Ectopic Lymphoid Structure Formation In Lacrimal Glands Of A Sjögren’S Disease Murine Model, Sara Abdelhamid, Alison V Ramirez, Emre Aksan, Elizaveta A Demianova, Cintia S De Paiva, Maria C Edman, J Andrew Mackay, Sarah F Hamm-Alvarez

Faculty, Staff and Students Publications

Background: Sjögren's Disease (SjD) is a chronic autoimmune condition characterized by lymphocytic infiltration of lacrimal glands (LG) and salivary glands (SG). In SG, these immune structures have properties of ectopic lymphoid structures (ELS) and appear to play a critical role in disease pathology. While the presence of ELS in patients' SG biopsies is linked to disease severity, their presence and composition in LG has not been well characterized.

Methods: The properties and time course of apparent ELS development in LG from the male non-obese diabetes free (NOR) sub-strain of the Non-Obese Diabetic (NOD) mice was investigated at stages encompassing early …

Limosilactobacillus Reuteri Alleviates Proinflammatory T-Cell-Mediated Liver Injury And Transcriptomic Changes In Immunocompromised Mice, Ana Fadhel Alvarez, Zheng Yin, Beanna Okeugo, Alexander Banerjee, Meng Luo, Christopher M Taylor, Salomea Giorgberidze, Vaishali Harne, Rambabu Majji, Melissa N Munroe, Ji Ho Suh, Stephen T C Wong, Kang Ho Kim, Hari Krishna Yalamanchili, Suhair Al Salihi, Jon Marc Rhoads, Yuying Liu

Children’s Nutrition Research Center Staff Publications

Background: A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication.

Methods: To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Insulinemic And Inflammatory Dietary Patterns And Colorectal Cancer Risk: A Dietary Data Harmonization Study Of One Million Participants In The Consortium Of Metabolomics Studies (Comets), Ni Shi, Rachel Hoobler, Rhea Harewood, Amanda E Toland, Demetrius Albanes, Emmanouil Bouras, Marc J Gunter, Linda M Liao, Steven C Moore, Fulvio Ricceri, Jerome I Rotter, Rashmi Sinha, Rachael Stolzenberg-Solomon, Anne Tjønneland, Alexis C Wood, Danxia Yu, Mary C Playdon, Fred K Tabung

Children’s Nutrition Research Center Staff Publications

Background: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established.

Objectives: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk.

Methods: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and …

Evolving Burden Of Metabolic Dysfunction-Associated Steatotic Liver Disease And Its Complications In A Us Nationwide Healthcare System, Basim Ali, Ronald Samuel, Jennifer R Kramer, Liang Li, Xian Yu, Yumei Cao, Roxanne Desiderio, George Cholankeril, Steven M Asch, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. Measuring the burden of cirrhosis and its complications in people with MASLD is important to inform health care delivery.

Methods: We aimed to quantify the changes in the burden of MASLD-related cirrhosis and hepatocellular carcinoma (HCC) in a nationwide U.S. healthcare system. We used data from the Veterans Health Administration to examine temporal trends between 2010 and 2021 in the annual incidence and prevalence of cirrhosis and HCC in a large cohort of patients with MASLD, and to compare them to those in patients with hepatitis C …

Imagining Genomics And Population Health In 2050: Anticipating Future Research, Policy, And Governance Needs, Bartha Maria Knoppers, Yann Joly, Ma Apos N H Zawati, Habiba Alsafar, Jeffrey C Barrett, Laura Blackburn, Brian Hon-Yin Chung, Martina C Cornel, Edward S Dove, David Glazer, Calvin Wai-Loon Ho, Muin J Khoury, Anna C F Lewis, Anneke Lucassen, Peter F R Mills, Colin Mitchell, Nicola Mulder, Ainsley J Newson, Anthony Ng, Paul D P Pharoah, Vasiliki Rahimzadeh, Megan C Roberts, Saskia C Sanderson, Jeffrey M Skopek, Ron Zimmern, Eric M Meslin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Updates In The Management Of Peanut Allergy, S Shahzad Mustafa, Aikaterini Anagnostou, Matthew Greenhawt

Faculty, Staff and Students Publications

Peanut allergy is a significant rising public health problem affecting both children and adults. Early peanut introduction has been adopted in multiple westernized nations as a preventative strategic measure to reduce the risk of developing peanut allergy, although implementation faces barriers. Multiple therapies to treat peanut allergy have been developed, including oral immunotherapy and omalizumab as approved treatments to provide protection against reactions from accidental exposure and reduce the risk of anaphylaxis, offering options beyond strict avoidance. Strategies in the developmental pipeline include epicutaneous immunotherapy and sublingual immunotherapy. The future is bright for individuals with peanut allergy, as these breakthroughs …

The Structure Of The Native Cardiac Crossbridge In The Rigor State, Cristina M. Risi, Tyler Nguyen, Betty Belknap, Howard D. White, Jose R. Pinto, Prescott B. Chase, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Cardiac contraction is driven by double-headed myosin cycling on cardiac thin filaments, where troponin-tropomyosin regulates myosin access to actin. Prior high-resolution structural studies used a single-headed myosin bound to bare actin, thereby limiting insight into coordination between myosin heads and the influence of troponin-tropomyosin on actomyosin interactions. Here, we report a high-resolution structure of the native cardiac rigor cross-bridge formed by heavy meromyosin bound to the thin filament. We show that direct communication between the two bound heads, uneven interactions between the heads and tropomyosin, and spatial constraints imposed by troponin govern myosin placement along the thin filament. Additionally, the …

Deep Reinforcement Learning–Driven Multi-Omics Integration For Constructing Gtage: A Novel Aging Clock From Igg N-Glycome And Blood Transcriptome, Yao Xia, Syed Mohammed Shamsul Islam, Xingang Li, Abdul Baten, Xuerui Tan, Wei Wang

Research outputs 2022 to 2026

Previous studies have demonstrated that the immunoglobulin G (IgG) N-glycome and transcriptome are potential biochemical signatures of chronological and biological ages, and several aging clocks have been developed. By integrating the IgG N-glycome and transcriptome, we propose a novel aging clock, gtAge. We developed a deep reinforcement learning-based multiomics integration method called AlphaSnake. The results showed that AlphaSnake achieved a predicted coefficient of determination (R²) value of 0.853, outperforming the concatenation-based integration method (R² = 0.820). The gtAge estimated by AlphaSnake explained up to 85.3% of the variance in chronological age, which was higher than that in …

Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer’s disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial–SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most …

Meta-Analysis Of Dna Methylation Aging Signatures In 17 Human Tissues, Macsue Jacques, Kirsten Seale, Sarah Voisin, Anna Lysenko, Robin Grolaux, Bernadette Jones-Freeman, Severine Lamon, Mandhri Abeysooriya, Itamar Levinger, Carlie Bauer, Adam P. Sharples, Aino Heikkinen, Elina Sillanpaa, Miina Ollikainen, Cassandra Smith, James R. Broatch, Navabeh Zarekookandeh, Linn Gillberg, Ida Blom, Jesse R. Poganik, Mahdi Moqri, Vadim N. Gladyshev, Matthew Taper, Cassandra Malecki, Sean Lal, Nathalie Saurat, Steve Horvath, Andrew Teschendorff, Nir Eynon

Research outputs 2022 to 2026

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD⁺ metabolism, supporting NAD⁺ as a potential therapeutic target in …

Empowering Through Structured Boundaries: An Integral Model For Fostering Balanced Eating And Nutritional Well-Being, Citrine Elatrash, Colleen Macke, Jenna Shi, Theresa Wilson, Sarah H Elsea, Stephanie Sisley

Faculty, Staff and Students Publications

Purpose: Treating obesity in complex disorders requires individualized health management plans. Effective obesity management in the Smith-Magenis syndrome (SMS) population has multiple inherent barriers related to their cognitive impairments, anxiety, behavioral disturbances, and sleep disorders. However, to date, no research exists related to strategies caregivers successfully employ to help individuals with SMS manage their food intake and mitigate associated behaviors.

Methods: We performed a qualitative thematic analysis of group interviews from 23 caregivers representing 21 individuals with SMS. Hybrid thematic analysis revealed that successful strategies employed by caregivers in this unique population revolved around a global theme of Empowering Through …