Medicine and Health Sciences Commons^™

Bowel Emergencies In Patients With Cancer, Hannah Hughes, Ankush Jajodia, Philippe Soyer, Vincent Mellnick, Michael N Patlas

2020-Current year OA Pubs

Cancer is the second most common cause of death worldwide. Bowel emergencies in patients with cancer are becoming increasingly more prevalent due to advances in cancer therapy and longer overall patient survival. When these patients present acutely, they are often frail and may have pre-existing co-morbidities. This article discusses the imaging features of bowel emergencies commonly encountered in oncological patients in clinical practice. These include chemotherapy related colitis, neutropenia enterocolitis and typhlitis, toxic megacolon, bowel perforation, malignant bowel obstruction and gastrointestinal haemorrhage. The radiologist plays a key role in identifying these oncological emergencies and guiding further management.

Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the …

Beta-Blockers After Pci For Stable Coronary Artery Disease And Preserved Left Ventricular Ejection Fraction, Safi U Khan, Usman Ali Akbar, Muhammad Shahzeb Khan, Kershaw V Patel, Amna Nadeem, Samarth Thakkar, Hassaan B Arshad, Salim S Virani, Khurram Nasir, Sachin S Goel, Alpesh R Shah, William Zoghbi, Neal S Kleiman

Faculty, Staff and Students Publications

Background: Limited data exist on the long-term impact of beta-blocker therapy after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF).

Objectives: The aim of the study was to evaluate the effects of early beta-blocker initiation vs no initiation following PCI in patients with stable CAD and preserved LVEF.

Methods: This retrospective cohort study employed target trial emulation and incident user design, utilizing the TriNetx database (2009-2024). Early beta-blocker initiation (within days 1 and 7) was compared with no initiation using 1:1 greedy propensity score matching. The outcomes included all-cause …

Testosterone Modulation Of Muscle Transcriptomic Profile During Lifestyle Therapy In Older Men With Obesity And Hypogonadism, Viola Viola, Tagari Samanta, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Ngoc Ho Lam Nguyen, Georgia Colleluori, Yoann Barnouin, Nicola Napoli, Clifford Qualls, Benny Abraham Kaipparettu, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Testosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight-loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.

Objective: To investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high-risk older population.

Methods: Among 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently < 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26-week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.

Results: Despite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (-2% vs. -4%, respectively; p = …

Sustainable Solutions To The Continuous Threat Of Antimicrobial Resistance, Brad Spellberg, David N Gilbert, Michael Baym, Gonzalo Bearman, Tom Boyles, Arturo Casadevall, Graeme N Forrest, Sarah Freling, Bassam Ghanem, Fergus Hamilton, Brian Luna, Jessica Moore, Daniel M Musher, Travis B Nielsen, Priya Nori, Matthew C Phillips, Liise-Anne Pirofski, Andrew F Shorr, Steven Y C Tong, Todd C Lee, Emily G Mcdonald

Faculty, Staff and Students Publications

To combat antimicrobial resistance (AMR), advocates have called for passage of the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act in the United States, which would appropriate $6 billion in new taxpayer-funded subsidies for antibiotic development. However, the number of antibiotics in clinical development, and US Food and Drug Administration approvals of new antibiotics, have already markedly increased in the last 15 years. Thus, instead of focusing on more economic subsidies, we recommend reducing selective pressure driving AMR by (1) establishing pay-for-performance mechanisms that disincentivize overprescribing of antibiotics, (2) focusing existing research and development funding on strategies that decrease …

Oral Anticoagulant Initiation In Patients With Kidney Failure On Hemodialysis Newly Diagnosed With Atrial Fibrillation (2007-2020): An Observational Study Of Trends And Disparities, Wolfgang C Winkelmayer, Austin Hu, Pascale Khairallah, Medha Airy, Kevin F Erickson, Tara I Chang, Jingbo Niu

Faculty, Staff and Students Publications

Rationale & objective: Atrial fibrillation (AF) is common in patients with kidney failure on hemodialysis (HD), but few patients receive oral anticoagulant (OAC) treatment. Availability of direct-target OACs starting in 2010 may have induced greater OAC initiation, but this has not been systematically studied.

Study design: Retrospective cohort study.

Setting & participants: Using Medicare fee-for-service billing claims (2006-2020), we identified previously OAC-naïve HD patients newly-diagnosed with AF between January 1, 2007, and October 1, 2020.

Exposures: Calendar year; race/ethnicity.

Outcomes: OAC initiation within 90 days from AF diagnosis (any; specific agent).

Analytical approach: We estimated initiation risk ratios for each …

Disease Activity Of Rheumatoid Arthritis And Kidney Function Decline: A Large Prospective Registry Study, Sho Fukui, Wolfgang C Winkelmayer, Sara K Tedeschi, Javier Marrugo, Hongshu Guan, Leslie Harrold, Heather J Litman, Tomohiro Shinozaki, Daniel H Solomon

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is a common comorbidity of rheumatoid arthritis (RA). The association of longitudinal RA disease activity with long-term kidney function has remained uncertain.

Method: We analysed a multicentre prospective RA registry in the USA from 2001 to 2022. The exposure was updated time-averaged Clinical Disease Activity Index (TA-CDAI) categories from study enrolment. The primary outcome was a longitudinal estimated glomerular filtration rate (eGFR) change. Secondary outcomes included developments of CKD stage G3a (eGFR< 60 mL/min/1.73 m2) and stage G3b (eGFR< 45 mL/min/1.73 m2). Results were adjusted for relevant time-fixed and time-varying covariates.

Results: 31 129 patients (median age: 58.0 years, female: 76.3%, median eGFR: 90.7 mL/min/1.73 m2) contributed 234 973 visits and 146 778 person-years …

Intercostal Nerve Cryoablation In Lung Transplantation: A Single-Center, Propensity Score-Matched Analysis, Marcelo Salan-Gomez, Ramiro Fernandez, Ethan D'Silva, Belia Camarena, Emma Hills, Andres Leon, Syed B Peer, Abdussalam Elsenousi, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Background: Achieving adequate pain control after lung transplantation is an essential milestone in a patient's recovery. We compared postoperative opioid use, clinical outcomes, and respiratory function in lung transplant recipients treated with intercostal nerve cryoablation (INC) compared to those receiving standard pain management.

Methods: We reviewed all adult lung transplants performed at our center between January 2016 and December 2022. We excluded cases performed through median sternotomy and patients with prior thoracotomies, multiorgan transplants, and redo transplants. We performed a propensity score-matched analysis, comparing patients who received INC versus those who received standard pain management. The primary outcome was cumulative …

A Staged Approach To Resecting A Large Rectal Polyp Using Endoscopic Mucosal Resection And Trans-Anal Endoscopic Microsurgery: A Case Report, Bhavna A Guduguntla, Jared Yee, Paul E Wise, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Large rectal adenomatous polyps are not uncommon. Proctectomy sparing interventions are favored when feasible. We present a case of a 62-year-old woman, who presented with diarrhea for several years. Colonoscopy revealed a very large 60 mm rectal polyp, biopsied as tubulovillous adenoma. This was successfully resected using a staged approach with endoscopic mucosal resection and trans-anal endoscopic microsurgery. Endoscopic mucosal resection removed 70% of the lesion with central scarred not amenable to resection but amenable to transanal excision. Pathology demonstrated tubulovillous adenoma with negative margins. Flexible sigmoidoscopy at 6-month follow-up revealed well healed scar without recurrence or residual disease. This …

Nuclear Egfr In Breast Cancer Suppresses Nk Cell Recruitment And Cytotoxicity, Angelica Escoto, Ryan Hecksel, Chance Parkinson, Sara Crane, Benjamin Atwell, Shyanne King, Daniela Ortiz Chavez, Alison Jannuzi, Barbara Sands, Benjamin G Bitler, Todd A Fehniger, Andrew L Paek, Megha Padi, Joyce Schroeder

2020-Current year OA Pubs

Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. The epidermal growth factor receptor (EGFR) is a potent oncogene that can activate survival, migration, and proliferation pathways, and clinical data suggests it may also play an immunomodulating role in cancers. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain. Using a novel peptide therapeutic (cSNX1.3) that inhibits retrograde trafficking of EGFR and an EGFR nuclear localization mutant, we discovered that nEGFR suppresses NK cell recruitment and cytotoxicity. RNA-Seq …

Triacylglycerol Mobilization Underpins Mitochondrial Stress Recovery, Zakery N Baker, Yunyun Zhu, Rachel M Guerra, Andrew J Smith, Aline Arra, Lia R Serrano, Katherine A Overmyer, Shankar Mukherji, Elizabeth A Craig, Joshua J Coon, David J Pagliarini

2020-Current year OA Pubs

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response. In particular, acyl chains from these stores were liberated by triacylglycerol lipases and used to fuel biosynthesis of the quintessential mitochondrial membrane lipid cardiolipin to support new mitochondrial …

Unprecedented Female Mutation Bias In The Aye-Aye, A Highly Unusual Lemur From Madagascar, Richard J Wang, Yadira Peña-García, Muthuswamy Raveendran, R Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D Yoder, Joe H Simmons, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality-without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to …

Historical Demography And Species Distribution Models Shed Light On Speciation In Primates Of Northeast India, Mihir Trivedi, Kunal Arekar, Shivakumara Manu, Lukas F K Kuderna, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet, Govindhaswamy Umapathy

Faculty, Staff and Students Publications

Past climate change is one of the important factors influencing primate speciation. Populations of various species could have risen or declined in response to these climatic fluctuations. Northeast India harbors a rich diversity of primates, where such fluctuations can be implicated. Recent advances in climate modeling as well as genomic data analysis has paved the way for understanding how species accumulate at a particular geographic region. We utilized these methods to explore the primate diversity in this unique region in relation to past climate change. To ascertain the population level changes, we inferred the demographic history of nine species of …

Hospice Patients In The Emergency Department: Challenging High-Risk Encounters With Unanswered Questions And Unquestioned Answers, Jason K Bowman, Joan M Teno, Kei Ouchi

Faculty, Staff and Students Publications

No abstract provided.

The Efficacy Of Complementary And Alternative Medicines In Medical Dermatology: A Comprehensive Review, Promise Ufomadu, Bartley Joseph Gill, Ida Orengo, Theodore Rosen, Ikue Shimizu

Faculty, Staff and Students Publications

Background: In recent years, there has been a widespread patient use of complementary and alternative medicines (CAMs) for dermatological application, despite few RCT-level studies on these supplements. This creates a barrier for dermatologists and others in counseling patients who may be using or might be tempted to use these CAM agents. This review investigates various CAM modalities used by patients for medical dermatology, exploring their efficacy and toxicity profiles.

Methods: A comprehensive review was performed on the effectiveness of several CAMs utilized in medical dermatology by patients. A literature search was conducted using PubMed, Embase, Google Scholar, Web of Science, …

Improving Outcomes Of Depression Through Implementation Of Depression Screenings At A College Health Center, Shelby Leigh Hanigan

Electronic Theses and Dissertations

Depression is a common phenomenon. Depression and suicidality are a problem on university campuses. This quality improvement Doctor of Nursing project aimed to establish the importance of routine depression screenings within a college health clinic. The purpose of this project was to determine if implementing routine depression screenings at a university health clinic will or will not increase the number of counseling referrals when compared to the absence of depression screenings in place within an identified timeframe. This protocol screened for depression in college-aged students and suggested care to those students who screened positive. It also led an interprofessional team …

Kras Mutations In Cancer: Understanding Signaling Pathways To Immune Regulation And The Potential Of Immunotherapy, Priyanka Uniyal, Vivek Kumar Kashyap, Tapan Behl, Deepak Parashar, Ravi Rawat

School of Medicine Publications

The Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation is one of the most prevailing mutations in various tumors and is difficult to cure. Long-term proliferation in carcinogenesis is primarily initiated by oncogenic KRAS-downstream signaling. Recent research suggests that it also activates the autocrine effect and interplays the tumor microenvironment (TME). Here, we discuss the emerging research, including KRAS mutations to immune evasion in TME, which induce immunological modulation that promotes tumor development. This review gives an overview of the existing knowledge of the underlying connection between KRAS mutations and tumor immune modulation. It also addresses the mechanisms to reduce …

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers, Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Methods: Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene …

Ethical Governance For Genomic Data Science In The Cloud, Vasiliki Rahimzadeh, Sarah C Nelson, Adrian Thorogood, Jonathan Lawson, Stephanie M Fullerton

Center for Medical Ethics and Health Policy Staff Publications

Cloud platforms offer distinct advantages, but questions remain about how to ethically and efficiently manage human genomic data in the cloud. Data governance needs to be adapted to ensure transparency and security for research participants, as well as equitable and sustainable access for researchers.

Resilience And Coping: A Qualitative Analysis Of Cognitive And Behavioral Factors In Adults With Osteogenesis Imperfecta, Hannah E Cho, Whitney S Shepherd, Gianna M Colombo, Andrew D Wiese, W Conor Rork, Kristin M Kostick, Dianne Nguyen, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Justin H Qian, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI).

Materials and methods: Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI.

Results: Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping …

Synaptic Alterations In Pyramidal Cells Following Genetic Manipulation Of Neuronal Excitability In Monkey Prefrontal Cortex, Guillermo Gonzalez-Burgos, Takeaki Miyamae, Yosuke Nishihata, Olga L Krimer, Kirsten Wade, Kenneth N Fish, Dominique Arion, Zhao-Lin Cai, Mingshan Xue, William R Stauffer, David A Lewis

Duncan NRI Faculty and Staff Publications

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

Mid-Life Anti-Inflammatory Metabolites Are Inversely Associated With Long-Term Cardiovascular Disease Events, Anum Saeed, Chris Mckennan, Jiaxuan Duan, Yueh-Ning Yang, Kevin E Kip, David Finegold, Michael Vu, Justin Swanson, Oscar L Lopez, Ann Cohen, Mark Mapstone, Bing Yu, Christie M Ballantyne, Steven E Reis

Faculty, Staff and Student Publications

BACKGROUND: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

METHODS: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes …

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Association Between Maternal Stress And Child Sleep Quality: A Nationwide Echo Prospective Cohort Study, Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique Lebourgeois, Kaja Z Lewinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz

Children’s Nutrition Research Center Staff Publications

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures.

Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association.

Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression …

Gout Versus Pseudogout In The Medically Underserved Rio Grande Valley, Blake Martin, Fernando Cisneros, Kristina Vatcheva, Michael Sander

School of Medicine Publications

Background

Gout and pseudogout are inflammatory joint conditions, with gout being one of the most prevalent etiologies of chronic inflammatory arthritis in the United States. The patient population in the Rio Grande Valley (RGV) has a distinct demographic profile that warrants the exploration of various health conditions. The primary objective of this study was to expand the knowledge of orthopedics and determine if there were demographic disparities between gout and pseudogout in this community. We hypothesized that there would be demographic disparities between gout and pseudogout depending on age, sex, and ethnicity.

Methods

This was a retrospective chart review, and …

Hear Ye, Hear Ye, Camaraderie For All, Michelle C. Dziurgot

The Journal of the Michigan Dental Association

The 2025 Michigan Dental Association Annual Session returns to Detroit from April 23-26, 2025, at the Renaissance Center. This premier event offers continuing education (CE) courses, social gatherings, and keynote speakers. Attendees can earn up to 18 CE credits across specialized tracks, including leadership, new dentists, and dental business professionals. Featured events include the MDA Foundation Sparkling Smiles Celebration, a Women’s Leadership Event, and keynotes by Hoan Do and Sean Astin. With networking, entertainment, and professional growth opportunities, this event is a must for the dental community.

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

A Statistical Framework For Multi-Trait Rare Variant Analysis In Large-Scale Whole-Genome Sequencing Studies, Xihao Li, Han Chen, Margaret Sunitha Selvaraj, Eric Van Buren, Hufeng Zhou, Yuxuan Wang, Ryan Sun, Zachary R Mccaw, Zhi Yu, Min-Zhi Jiang, Daniel Dicorpo, Sheila M Gaynor, Rounak Dey, Donna K Arnett, Emelia J Benjamin, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, April P Carson, Jenna C Carlson, Nathalie Chami, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Myriam Fornage, Nora Franceschini, Barry I Freedman, Charles Gu, Nancy L Heard-Costa, Jiang He, Lifang Hou, Yi-Jen Hung, Marguerite R Irvin, Robert C Kaplan, Sharon L R Kardia, Tanika N Kelly, Iain Konigsberg, Charles Kooperberg, Brian G Kral, Changwei Li, Yun Li, Honghuang Lin, Ching-Ti Liu, Ruth J F Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alexander P Reiner, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Hemant K Tiwari, Ramachandran S Vasan, Satupa'itea Viali, Zhe Wang, Jennifer Wessel, Lisa R Yanek, Bing Yu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Josée Dupuis, James B Meigs, Paul L Auer, Laura M Raffield, Alisa K Manning, Kenneth M Rice, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Zilin Li, Zhonghua Liu, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple …

Serotonin Neurons Integrate Gaba And Dopamine Inputs To Regulate Meal Initiation, Kristine M Conde, Hueyzhong Wong, Shuzheng Fang, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Hailan Liu, Na Yin, Jonathan C Bean, Junying Han, Megan E Burt, Sanika V Jossy, Yongjie Yang, Qingchun Tong, Benjamin R Arenkiel, Chunmei Wang, Yang He, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays a role in meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger. Additionally, …

Leptin Receptor Neurons In The Dorsomedial Hypothalamus Require Distinct Neuronal Subsets For Thermogenesis And Weight Loss, Marie Francois, Laura Kaiser, Yanlin He, Yong Xu, J Michael Salbaum, Sangho Yu, Christopher D Morrison, Hans-Rudolf Berthoud, Heike Münzberg

Children’s Nutrition Research Center Staff Publications

The dorsomedial hypothalamus (DMH) receives inputs from the preoptic area (POA), where ambient temperature mediates physiological adaptations of energy expenditure and food intake. Warm-activated POA neurons suppress energy expenditure via brown adipose tissue (BAT) projecting neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA). Our earlier work identified leptin receptor (Lepr)-expressing, BAT-projecting dDMH/DHA neurons that mediate metabolic leptin effects. Yet, the neurotransmitter (glutamate or GABA) used by dDMH/DHALepr neurons remains unexplored and was investigated in this study using mice. We report that dDMH/DHALepr neurons represent equally glutamatergic and GABAergic neurons. Surprisingly, chemogenetic activation of glutamatergic and/or GABAergic dDMH/DHA neurons were capable …