Digital Commons Network^™

Rest-Activity Rhythm Phenotypes In Adults With Epilepsy And Intellectual Disability, Nandani Adhyapak, Grace E Cardenas, Mark A Abboud, Vaishnav Krishnan

Faculty, Staff and Students Publications

Objective: Rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe RAR perturbations in intellectually disabled adults with epilepsy ("E + ID"), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function, and/or comorbid psychopathology.

Methods: Caregivers of E + ID subjects provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers …

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Construct And Predictive Validity Of The Kansas City Cardiomyopathy Questionnaire In Adult Congenital Heart Disease, Ryan D Byrne, Ajith P Nair, Stephen J Dolgner, Swati Choudhry, Edward J Hickey, Alexis C Wood, Savitri Fedson, Biykem Bozkurt, Christopher R Broda

Faculty, Staff and Students Publications

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is an Food and Drug Administration-approved health status measure for patients with heart failure (HF) but has not been directly assessed in adult congenital heart disease (ACHD).

Objectives: This study evaluates construct and predictive validity of the KCCQ in ambulatory ACHD patients.

Methods: We performed cross-sectional and prospective cohort studies of ACHD patients who completed the KCCQ to assess construct and predictive validity, respectively. KCCQ scores were compared across ACHD complexity categories, disease characteristics and physiologic failure, and within 2 primary composite outcomes: death or all-cause hospitalization (DH) and death or interventional cardiac …

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Domains Of Housing Instability And Intimate Partner Violence Risk Among U.S. Tenants, Anairany Zapata, Leila G Wood, Annalynn M Galvin, Wenyaw Chan, Timothy A Thomas, Jack Tsai, Heather K Way, Elizabeth J Mueller, Daphne C Hernandez

Faculty, Staff and Student Publications

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. …

No Evidence Of Pitavastatin Effect On Muscle Area Or Density Among People With Hiv, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Michael T Lu, Jana Taron, Marissa R Diggs, Pamela S Douglas, Kathleen V Fitch, Carl J Fichtenbaum, Markella V Zanni, Judith A Aberg, Maria C Rodriguez-Barradas, Katharine Breaux, Rosalba Gomez Morones, Craig A Sponseller, Judith S Currier, Gerald S Bloomfield, Sarah M Chu, Alex B Lu, Carlos D Malvestutto, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Skeletal muscle area (MA) and muscle density (MD) are key determinants of physical function and typically decline with increasing age. Statins have well-known musculoskeletal effects but whether statins impact MA or MD is not well established, especially in the setting of randomized treatment.

Methods: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus MA and MD were assessed among Mechanistic Substudy participants with CT at baseline and month 24.

Results: Of 804 substudy participants, 510 remained on study treatment …

No Evidence Of Pitavastatin Effect On Muscle Area Or Density Among People With Hiv, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Michael T Lu, Jana Taron, Marissa R Diggs, Pamela S Douglas, Kathleen V Fitch, Carl J Fichtenbaum, Markella V Zanni, Judith A Aberg, Maria C Rodriguez-Barradas, Katharine Breaux, Rosalba Gomez Morones, Craig A Sponseller, Judith S Currier, Gerald S Bloomfield, Sarah M Chu, Alex B Lu, Carlos D Malvestutto, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Skeletal muscle area (MA) and muscle density (MD) are key determinants of physical function and typically decline with increasing age. Statins have well-known musculoskeletal effects but whether statins impact MA or MD is not well established, especially in the setting of randomized treatment.

Methods: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus MA and MD were assessed among Mechanistic Substudy participants with CT at baseline and month 24.

Results: Of 804 substudy participants, 510 remained on study treatment …

Acute Respiratory Distress Syndrome In Patients With Lymphopenia: Results From The National Inpatient Sample (2017-2021), Arnav Garyali, Trishna Parikh, Dhruv Kumar, Ishan Gupta, Adishwar Rao, Akriti Agrawal, Sabiha Armin, Rishi Panjala, Rohan Patil, Nikhil Sriram, Sruthi Parthasarathy, Aarohi Parikh, Bindu Akkanti

Faculty, Staff and Student Publications

Background: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population.

Methods: Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017-2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model.

Results: From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered …

Patient-Centered, Theory-Based, Online Intervention To Promote A Physically Active Lifestyle For People With Multiple Sclerosis: Protocol For A Randomized Controlled Trial, Chungyi Chiu, Vaishnavi Sridharan, Mojtaba Khaliji, Md Refat Uz Zaman Sajib, Xiaotian Gao, Kathleen Zackowski

Children’s Nutrition Research Center Staff Publications

Background: People with multiple sclerosis (MS) experience life challenges due to the nature of disease progression. Although an active lifestyle has been shown effective for symptom and relapse management, most people with MS lead a sedentary lifestyle and do not reach the recommended physical activity (PA) guidelines.

Objective: This study aims to test the preliminary efficacy of a codeveloped, online self-management intervention based on the health action process approach (HAPA) adapted for people with MS to cultivate a physically active lifestyle.

Methods: The 8-week intervention program was developed using community-based participatory research based on the HAPA. The program includes increasing …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

Role Of Lipoprotein(A) In Atherosclerotic Cardiovascular Disease In South Asian Individuals, Darshan Patel, Marlys L Koschinsky, Anandita Agarwala, Pradeep Natarajan, Harpreet S Bhatia, Anurag Mehta, Jaideep Patel, Matthew Peters, Shreya Pandya, Usman Sagheer, Raman Puri, Salim S Virani, Dinesh K Kalra

Faculty, Staff and Students Publications

South Asian individuals (SA), representing approximately one quarter of the global population, experience a disproportionately high burden of cardiovascular disease. Some of this increased susceptibility is accounted for by traditional risk factors such as diabetes, hypertension, carbohydrate-rich diets, and rising rates of obesity and metabolic syndrome. However, other previously underappreciated risk factors may also play a crucial role. These include environmental pollution, genetic factors, and Lp(a) (lipoprotein(a)). Various epidemiological and genetic studies support the role of Lp(a) as a causal and independent risk factor for atherosclerotic cardiovascular disease. SA have a higher prevalence of elevated Lp(a) levels (25% have levels …

Exogenous Arginine Differentially Regulates Inflammatory Cytokine And Inducible Nitric Oxide Synthase Expression In Macrophages, Kelsey Stayer, Saliha Pathan, Aalekhya Biswas, Huiqiao Li, Yi Zhu, Fong Wilson Lam, Juan Marini, Sundararajah Thevananther

Faculty, Staff and Students Publications

Immune dysfunction and late mortality from multiorgan failure are hallmarks of severe sepsis. Arginine, a semi-essential amino acid important for protein synthesis, immune response, and circulatory regulation, is deficient in sepsis. However, arginine supplementation in sepsis remains controversial due to the potential to upregulate inducible nitric oxide synthase (iNOS)-mediated excessive nitric oxide (NO) generation in macrophages, leading to vasodilation and hemodynamic catastrophe. Citrulline supplementation has been considered an alternative to replenishing arginine via de novo synthesis, orchestrated by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). However, the functional relevance of the ASS1-ASL pathway in macrophages after endotoxin stimulation is …

The Overlooked Impact Of Background Diet And Adherence In Nutrition Trials, Javier I Ottaviani, Hagen Schroeter, Dennis M Bier, John W Erdman, Howard D Sesso, Joann E Manson, Gunter G C Kuhnle

Children’s Nutrition Research Center Staff Publications

Randomised controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address these challenges. Using flavanols as a model dietary intervention and a set of recently validated flavanol biomarkers, we here investigated the impact of background diet and adherence on the outcomes of a subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS, NCT 02422745). We found that 20% of participants …

The Feasibility Of Passively Tracking Children’S Tv Viewing And Mobile Device Use In Naturalistic Settings, Teresia M O'Connor, Tatyana Garza, Uzair Alam, Anil Kumar Vadathya, Jennette P Moreno, Alicia Beltran, Samah Haidar, Nimah Haidar, Sheryl O Hughes, Debbe Thompson, Salma M A Musaad, Tom Baranowski, Jason A Mendoza, Joseph Young, Akane Sano, Ashok Veeraraghavan

Faculty, Staff and Students Publications

Research on children's technology and digital media (TDM) is hampered by a lack of robust approaches for assessing TDM use. This study assessed the feasibility of passively measuring children's TV screens and mobile devices (TDM) in a naturalistic setting. In the three-day feasibility study, FLASH-TV was set up on one to two TVs the child (5-12 year olds) typically used in the home (n=20). Children's mobile device use was assessed with either the Chronicle App or ScreenTime screenshots. Parents completed three TDM diaries. An exit interview with the parent explored their perceptions of the assessments and the child's TDM use …

The Current And Future Burden Of Long Covid In The United States, Sarah M Bartsch, Kevin L Chin, Ulrich Strych, Danielle C John, Tej D Shah, Maria Elena Bottazzi, Kelly J O'Shea, Mckaylee Robertson, Colleen Weatherwax, Jessie Heneghan, Marie F Martinez, Allan Ciciriello, Sarah Kulkarni, Kavya Velmurugan, Alexis Dibbs, Sheryl A Scannell, Yanhan Shen, Denis Nash, Peter J Hotez, Bruce Y Lee

Faculty, Staff and Students Publications

Background: Long coronavirus disease (COVID), which affects an estimated 44.69-48.04 million people in the United States, is an ongoing public health concern that will persist as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread.

Methods: We developed a computational simulation model representing the clinical course, health effects, and associated costs of a person with long COVID.

Results: Simulations show that the average total cost of a long COVID case can range from $5084-$11 646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of long COVID cases could cost …

Mir-302a/B/D-3p Differentially Expressed During Frontonasal Development Is Sensitive To Retinoic Acid Exposure, Chihiro Iwaya, Akiko Suzuki, Goo Jun, Junichi Iwata

Faculty, Staff and Student Publications

Any failure in frontonasal development can lead to malformations at the middle facial region, such as frontonasal dysplasia, midfacial clefts, and hyper/hypotelorism. Various environmental factors influence morphogenesis through epigenetic regulations, including the action of noncoding microRNAs (miRNAs). However, it remains unclear how miRNAs are involved in the frontonasal development. In our analysis of publicly available miRNA-seq and RNA-seq datasets, we found that miR-28a-5p, miR-302a-3p, miR-302b-3p, and miR-302d-3p were differentially expressed in the frontonasal process during embryonic days 10.5 to 13.5 (E10.5–E13.5) in mice. Overexpression of these miRNAs led to a suppression of cell proliferation in cultured mouse embryonic frontonasal mesenchymal …

Src/Fn1 Pathway Activation Drives Tumor Cell Cluster Formation And Metastasis In Lung Cancer: A Promising Therapeutic Target, Zujun Que, Zhichao Xi, Dan Qi, Rongchen Dai, Yang Li, Mengfan Liu, Bin Luo, Jiajun Liu, Pan Yu, Yun Yang, Erxi Wu, Hongxi Xu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)-particularly clusters-being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical …

Global Diversity Of Soil-Transmitted Helminths Reveals Population-Biased Genetic Variation That Impacts Diagnostic Targets, Marina Papaiakovou, Andrea Waeschenbach, Olumide Ajibola, Sitara Sr Ajjampur, Roy M Anderson, Robin Bailey, Jade Benjamin-Chung, Maria Cambra-Pellejà, Nicolas R Caro, David Chaima, Rubén O Cimino, Piet Cools, Anélsio Cossa, Julia Dunn, Sean Galagan, Javier Gandasegui, Berta Grau-Pujol, Emma L Houlder, Moudachirou Ibikounlé, Timothy P Jenkins, Khumbo Kalua, Eyrun F Kjetland, Alejandro J Krolewiecki, Bruno Levecke, Adrian Jf Luty, Andrew S Macdonald, Inácio Mandomando, Malathi Manuel, Maria Martínez-Valladares, Rojelio Mejia, Zeleke Mekonnen, Augusto Messa, Harriet Mpairwe, Osvaldo Muchisse, Jose Muñoz, Pauline Mwinzi, Valdemiro Novela, Maurice R Odiere, Charfudin Sacoor, Judd L Walson, Steven A Williams, Stefan Witek-Mcmanus, D Timothy J Littlewood, Cinzia Cantacessi, Stephen R Doyle

Faculty, Staff and Students Publications

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We …

Distinct Systemic Impacts Of Aβ42 And Tau Revealed By Whole-Organism Snrna-Seq, Ye-Jin Park, Tzu-Chiao Lu, Tyler Jackson, Lindsey D Goodman, Lindsey Ran, Jiaye Chen, Chung-Yi Liang, Erin Harrison, Christina Ko, Xi Chen, Baiping Wang, Ao-Lin Hsu, Elizabeth Ochoa, Kevin F Bieniek, Shinya Yamamoto, Yi Zhu, Hui Zheng, Yanyan Qi, Hugo J Bellen, Hongjie Li

Faculty, Staff and Students Publications

Both neuronal and peripheral tissues become disrupted in Alzheimer's disease (AD). However, a comprehensive understanding of how AD impacts different tissues across the whole organism is lacking. Using Drosophila, we generated an AD Fly Cell Atlas (AD-FCA) based on whole-organism single-nucleus transcriptomes of 219 cell types from flies expressing AD-associated proteins, either human amyloid-β 42 peptide (Aβ42) or Tau, in neurons. We found that Aβ42 primarily affects the nervous system, including sensory neurons, while Tau induces accelerated aging in peripheral tissues. We identified a neuronal cluster enriched in Aβ42 flies, which has high lactate dehydrogenase (LDH) expression. This LDH-high cluster …

Infantile Pyknocytosis Revisited: Possible Familial Trend In A Study Of 9 Patients, Aileen Y Hu, Amy M Coffey, Jyotinder N Punia, Andrea N Marcogliese, Choladda V Curry, M Tarek Elghetany

Faculty, Staff and Students Publications

Context.—: Infantile pyknocytosis (IP) is an uncommon cause of transient neonatal hemolytic anemia and hyperbilirubinemia occurring in approximately 10% of cases of unexplained neonatal hemolytic anemia.

Objective.—: To study cases of IP with focus on long-term follow-up, perinatal events, and family history.

Design.—: Cases were prospectively identified during review of peripheral blood smears for neonatal hyperbilirubinemia during an 11-year period. Clinical and laboratory parameters, follow-up data, and family history were recorded.

Results.—: Nine cases of IP were identified from the morphologic recognition of pyknocytes and clinical and laboratory evidence of hemolysis, and included 6 males and 3 females. Age at …

Food Noise: Definition, Measurement, And Future Research Directions, Emily J Dhurandhar, Kevin C Maki, Nikhil V Dhurandhar, Theodore K Kyle, Sydney Yurkow, Misty A W Hawkins, Jon Agley, Emily H Ho, Lawrence J Cheskin, Thorkild I A Sørensen, Xi Rita Wang, David B Allison

Children’s Nutrition Research Center Staff Publications

The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail. The increase in public discourse about food noise has highlighted its potential significance, yet a formal clinical definition and method of measurement of …

The Benefits Of Exercise Training In Combination With Weight Loss Therapies, Bryan C Jiang, Dennis T Villareal

Faculty, Staff and Students Publications

The primary treatment for obesity involves calorie restriction (CR) to promote dietary weight loss achieved through interventions including behavioral modification, bariatric surgery, and antiobesity medications. In adults with obesity, CR-induced weight loss enhances physical function and improves quality of life, while also reducing the burden of various obesity-related chronic conditions, including hypertension, diabetes, obstructive sleep apnea, and atherosclerotic heart disease. However, it is also associated with a decline in lean mass and bone mineral density, which increases the risk of sarcopenia and osteoporosis. When performed alongside CR, progressive resistance training (RT) attenuates this loss of lean mass and bone mass, …

Psilocybin Treatment Extends Cellular Lifespan And Improves Survival Of Aged Mice, Kosuke Kato, Jennifer M Kleinhenz, Yoon-Joo Shin, Cristian Coarfa, Ali J Zarrabi, Louise Hecker

Faculty, Staff and Students Publications

Psilocybin, the naturally occurring psychedelic compound produced by hallucinogenic mushrooms, has received attention due to considerable clinical evidence for its therapeutic potential to treat various psychiatric and neurodegenerative indications. However, the underlying molecular mechanisms remain enigmatic, and few studies have explored its systemic impacts. We provide the first experimental evidence that psilocin (the active metabolite of psilocybin) treatment extends cellular lifespan and psilocybin treatment promotes increased longevity in aged mice, suggesting that psilocybin may be a potent geroprotective agent.

Risk Of Pancreatic Cancer In Glycemically Defined New-Onset Diabetes: A Prospective Cohort Study, Suresh T Chari, Bechien Wu, Camden Lopez, Eva Lustigova, Qiaoling Chen, Stephen K Van Den Eeden, Amethyst D Leimpeter, William Fisher, Amy Wood, Ashley S Alexander, John Valenta, Santhi Swaroop Vege, Erin E Carlson, Kari G Rabe, Phil A Hart, Lu Qian, Ying-Qi Zhao, Nadia Yosuf, Lynn Matrisian, Barbara Kenner, Jo Ann Rinaudo, Anirban Maitra, Ziding Feng

Faculty, Staff and Student Publications

Background & aims: The increased 3-year incidence of pancreatic cancer after new-onset diabetes observed in retrospective studies needs prospective validation. It is unknown whether incidence varies by race and ethnicity.

Methods: In a prospective, observational study using active real-time surveillance of electronic health records, we identified 18,838 adults 50 years or older with glycemically defined new-onset diabetes (GNOD). In this interim analysis, we report 3-year Kaplan-Meier estimates of the proportion diagnosed with pancreatic cancer after GNOD (absolute incidence [95% CI]) and associated standardized incidence ratio (SIR) by race and ethnicity, overall 3-year incidence of pancreatic cancer adjusting for racial distribution …

Dopamine Partial Agonists In Pregnancy And Lactation: A Systematic Review, Alexia Koukopoulos, Delfina Janiri, Miriam Milintenda, Sara Barbonetti, Georgios D Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Marianna Mazza, Lucio Rinaldi, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani

Faculty, Staff and Students Publications

Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when …

Human Extravillous Trophoblasts Require Src-2 For Sustained Viability, Migration, And Invasion, Vineet K Maurya, Pooja Popli, Bryan C Nikolai, David M Lonard, Ramakrishna Kommagani, Bert W O'Malley, John P Lydon

Faculty, Staff and Students Publications

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential …

Vigorous Physical Activity As A Potential Environmental Risk Factor In Renal Medullary Carcinoma, Daniel D Shapiro, Sagar S Mukhida, Andrew W Hahn, Ayman Isahaku, Schyler M Turner, Jessica P Cheng, Pankaj K Chauhan, Susan S Thomas, Beei Chan, Zita D Lim, Nizar M Tannir, Maria Chang Swartz, Pavlos Msaouel

Faculty, Staff and Student Publications

Purpose: Renal medullary carcinoma (RMC) is a rare but aggressive kidney cancer affecting young individuals with sickle hemoglobinopathies. Prior retrospective case-control and mouse modeling studies suggest a mechanism linking vigorous intensity physical activity to increased RMC risk in individuals with sickle hemoglobinopathies. This study aimed to prospectively investigate the association between vigorous intensity exercise and RMC.

Materials and methods: This study used a validated questionnaire to prospectively assess reported physical activity in a large cohort of patients with RMC compared to the activity of individuals without RMC. Between 2022 and 2024, patients with RMC (N = 39) were prospectively surveyed …

Testosterone Deficiency And Treatments: Common Misconceptions And Practical Guidance For Patient Care, Mohit Khera, James M Hotaling, Martin Miner

Faculty, Staff and Students Publications

Introduction: Misconceptions about testosterone therapy are prevalent and there is an unmet need for a review of current literature that can be leveraged by physicians to deliver safe and effective care for men with hypogonadism.

Objectives: This review aims to address common misconceptions about testosterone therapy using current literature and synthesize practical guidance for clinicians with patients who are starting testosterone therapy.

Methods: A literature search of PubMed, Embase, CINAHL was carried out to identify associations between testosterone therapy and prostate cancer, cardiovascular risk, and hepatic toxicity; definitions of hypogonadism; and practical guidance for clinician with patients starting testosterone therapy. …

Genome-Wide Association Study For Lung Cancer In 6531 African Americans Reveals New Susceptibility Loci, Jinyoung Byun, Younghun Han, Jiyeon Choi, Ryan Sun, Vikram R Shaw, Catherine Zhu, Xiangjun Xiao, Christine Lusk, Hoda Badr, Hyun-Sung Lee, Hee-Jin Jang, Yafang Li, Hyeyeun Lim, Erping Long, Yanhong Liu, Linda Kachuri, Kyle M Walsh, John K Wiencke, Demetrius Albanes, Stephen Lam, Adonina Tardon, Marian L Neuhouser, Matt J Barnett, Chu Chen, Stig Bojesen, Hermann Brenner, Maria Teresa Landi, Mattias Johansson, Angela Risch, H-Erich Wichmann, Heike Bickeböller, David C Christiani, Gad Rennert, Susanne Arnold, John K Field, Sanjay Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Fiona Taylor, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Alpa Patel, Xihong Lin, Krista A Zanetti, Curtis C Harris, Stephen Chanock, James Mckay, Ann G Schwartz, Rayjean J Hung, Christopher I Amos

Faculty, Staff and Student Publications

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer …