Digital Commons Network^™

International Normative Charts For Twin Weight, Length, And Head Circumference At Birth, By Gestational Age And Sex: The Twin Neonatal Cross-Sectional Study Of The Intergrowth-21st Project, Francesca Giuliani, Sonia Deantoni, Enrico Bertino, Yasmin A. Jaffer, Manorama Purwar, Fernando C. Barros, Leila Cheikh Ismail, Wu Qingqing, Ilaria Stura, Maria Carvalho

Obstetrics and Gynaecology, East Africa

Assessing the size of twins at birth using charts developed for singletons may over diagnose small for gestational age in this sub-population. The study aimed to produce international, twin-specific, newborn size normative charts by gestational age and sex. This longitudinal observational study in eight geographically diverse settings prospectively collected data between May 2009 and August 2013 from healthy pregnant women and their newborn twins. The participants were enrolled as part of the INTERGROWTH-21st study, and recruited based on World Health Organization recommendations for evaluation of anthropometric measures. All the women met, in addition to the underlying population characteristics of low …

Mapping Social Determinants Of Health Data In Sub-Saharan Africa: A Scoping Review Protocol, Felix Anyiam, Jessica Gjonaj, Ngeresa Osango, Richard Mugo, Peace Aber, Jasmit Shah, Judith Mangeni, Rajesh Vedanthan, Joseph Hogan, Ann Mwangi

Internal Medicine, East Africa

Introduction Research has increasingly underscored the impact of factors such as socioeconomic status, education, healthcare access, housing and environmental conditions in shaping population health outcomes. These factors, collectively called social determinants of health (SDOH), provide crucial context for understanding drivers of health outcomes. In sub-Saharan Africa (SSA), the study of SDOH is critical due to the region’s unique sociocultural and economic conditions. Understanding how SDOH interacts with health systems and capturing SDOH in data is crucial for informing modelling efforts and policies improving population health more effectively. This scoping review aims to map the types of data used to capture …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

13 C-Spirulina Gastric Emptying Breath Test Normative Values In Healthy Children: A Multicenter Study With Comparison To Symptomatic Children, Katja Karrento, Bruno P Chumpitazi, Liyun Zhang, Pippa Simpson, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Diagnosing pediatric gastroparesis presents a significant challenge due to lack of normative data in children. We aimed to determine normative values for gastric emptying using the nonradioactive 13 C-Spirulina gastric emptying breath test ( 13 C-GEBT) in a large cohort of healthy children (HC) and examine differences compared to children with gastroparesis-like symptoms (GLS).

Methods: A total of 301 HC ages 7-18 years completed the 13 C-GEBT with 10 different breath samples × 4 hours. 13 CO 2 excretion rate (kPCD) was determined by change in 13 CO 2 / 12 CO 2 . Outcome variables included: kPCD at …

Participant Retention In A Prospective Multicenter Cohort Of Participants With Pancreatitis And Factors Associated With Attrition, Radmila Choate, Jun Xu, Jeffrey J Easler, Samuel Han, Anna E Phillips, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Liang Li, Darwin L Conwell, Dhiraj Yadav

Faculty, Staff and Students Publications

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP).

Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Secondary Prophylaxis Of Variceal Hemorrhage In Biliary Atresia-Analysis Of Prospective Multicenter Studies, Lee M Bass, Kieran Hawthorne, John C Magee, Benjamin L Shneider, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

No abstract provided.

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Internet-Delivered Cognitive-Behavioral Intervention For Pain In Pediatric Acute Recurrent And Chronic Pancreatitis: A Multicenter Randomized Controlled Trial, Tonya M Palermo, Rui Li, Chuan Zhou, Homer Aalfs, Gretchen Cress, Mark Lowe, Maisam Abu-El-Haija, Ankur Chugh, Elissa M Downs, Douglas S Fishman, Alvin Jay Freeman, Matthew J Giefer, Tanja Y Gonska, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Robert Adam Noel, Emily R Perito, Fuchenchu Wang, Ying Yuan, Yuhua Zheng, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Abdominal pain is common and associated with high disease burden and health care costs in pediatric acute recurrent (ARP) and chronic pancreatitis (CP). Despite the effectiveness of psychological interventions in other abdominal pain populations, studies have not evaluated these interventions for pediatric pancreatitis pain. We evaluated the feasibility, acceptability, and preliminary efficacy of internet-delivered cognitive-behavioral therapy (CBT) for reducing pancreatitis-related abdominal pain and improving pain interference, anxiety, depression, activity limitations, and health-related quality of life.

Methods: We enrolled 90 adolescents (ages 10-19, 63% female) with ARP or CP and their parents into this randomized placebo-controlled multicenter trial from 15 …

The Hidden Link Between Endometriosis And Obesity: A State-Of-The-Art Review, Shefali N Desai, Christina C Reed, Yamely Mendez, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Endometriosis remains an under-researched disease with a wide range of symptoms. Endometriosis reduces a woman's quality of life and professional productivity, yet its exact causes, risk factors, and treatment have yet to be elucidated. Body mass index and endometriosis have been observed to be inversely related; however, this relationship may only be a correlation rather than a causation. Obesity may play a role in the inflammation and cell proliferation associated with endometriosis through the complex signaling pathways of adipokines. A literature review was done on endometriosis and obesity to gain insight and synthesize knowledge about opportunities to improve endometriosis care, …

Utilization Of Intensive Care Interventions In Critically Ill Patients With Candidemia Versus Bacteremia: A Multicenter Retrospective Cohort Study, Mary North Jones, Masayuki Nigo, Stefano Casarin, James Kurian, Aarjav Sanghvi, Enshuo Hsu, Stephen L Jones, Ashton Connor, David B Corry, Cesar A Arias, Max W Adelman

Faculty, Staff and Students Publications

Objectives: Candida species are one of the most common causes of ICU-onset bloodstream infection (BSI). Yet, there is no robust guidance on when to initiate empiric antifungals for ICU patients suspected of BSI. We compared patients with ICU-onset candidemia vs. ICU-onset bacteremia to determine which patients may benefit from empiric antifungals.

Design: We compared characteristics between patients with bacteremia vs. candidemia at time of culture. We determined risk factors for death and constructed a multivariable regression to determine if candidemia is an independent risk factor for death.

Setting/patients: We included ICU patients from a hospital system in Houston, Texas (n …

Unusual Endoscopic Remission In An Anti-Tumor Necrosis Factor Refractory Case Of Severe Ulcerative Colitis During Upadacitinib Therapy, Carine A Halaby, Charlotte F Kim, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Evaluation Of Large Language Models As Decision Support Tools For Head And Neck Cancer Management: A Blinded Multidisciplinary Simulation Study, Sholem Hack, Ron J. Karni, Antonino Maniaci, Christopher E. Fundakowski, Luca Castellani, Fabiola Incandela, Remo Accorona, Miguel Mayo-Yanez, Martina Violati, Lorenzo Giannini, Niccolo' Mevio, Alberto Maria Saibene

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.

METHODS: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.

RESULTS: LLM outputs showed close alignment with expert recommendations. RAG-based …

Investigating The Risk Factors Affecting The Control Of Diabetes And Hypertension In The Refugees Living In Egypt, Noura Seada

Theses and Dissertations

Introduction: Non-Communicable Diseases (NCDs) account for 74% of global deaths, with high prevalence of Diabetes and Hypertension worldwide. Egypt hosts over 1 million registered refugees and asylum seekers, often lacking inclusion in social protection or insurance schemes. This study aimed to assess the factors affecting the control of Type 2 Diabetes (T2D) and Hypertension (HTN) among Syrian and Sudanese refugees in Egypt, focusing on healthcare access, sociodemographic characteristics, lifestyle, and health behaviours.

Methods: This study employed a cross-sectional design using a self-administered questionnaire and BMI measurement. Data were collected from 246 refugees diagnosed with type T2D and/or HTN in the …

Preoperative Malnutrition Is Associated With Increased Postoperative Complications Following Lumbar Fusion: A Propensity-Matched Analysis, Ali Mehaidli, Muaaz Wajahath, Jad Lawand, Omar Abdalla, Lorenzo Deveza, Noah Hodson, Ryan J Berger, Kevin Taliaferro

Faculty, Staff and Students Publications

Background: Lumbar fusion (LF) is a common surgical intervention for degenerative spinal conditions but carries significant short- and long-term risks. Preoperative malnutrition, characterized by low serum albumin or leukocyte counts, impairs wound healing and increases susceptibility to infection, yet its influence on LF outcomes remains underexplored. This study evaluates the association between preoperative malnutrition and long-term postoperative outcomes following LF.

Methods: Adult patients undergoing LF between 2003 and 2023 were identified in the TriNetX US Collaborative Network. Malnutrition was defined as serum albumin < 3.5 g/dL or leukocyte count < 1,500/mm3 within 1 year preoperatively. A 1:1 propensity score match was performed for demographics, comorbidities, surgical approach, and body mass index (BMI), yielding two cohorts (n=20,693 each). Ninety-day and 5‑year postoperative outcomes were compared using hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Malnourished patients experienced significantly higher 90‑day rates of transfusion (8.4% vs. 4.5%; HR 1.87, 95% CI: …

Unlocking Hope: Mirtazapine's Promise In Obsessive-Compulsive Disorder Treatment, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are first-line treatments for OCD, a significant proportion of patients remain refractory to these interventions. Mirtazapine, an atypical antidepressant with unique pharmacological properties, has emerged as a potential adjunctive therapy for treatment-resistant OCD. This review synthesizes existing evidence regarding the efficacy and safety profile of mirtazapine in OCD management. We analyze clinical trials, observational studies, and case reports, distinguishing high- vs. low-quality evidence, and discuss mechanisms underlying mirtazapine's therapeutic effects. Additionally, …

Clinical Outcomes Of Patients Hospitalized For Conventional Pacemaker Implantation With Protein-Energy Malnutrition, Phuuwadith Wattanachayakul, Pojsakorn Danpanichkul, Chalothorn Wannaphut, Hamza Tahir, John Malin, Thanathip Suenghataiphorn, Kanokphong Suparan, Aman Amanullah

Einstein Health Papers

INTRODUCTION: The impact of protein-energy malnutrition (PEM) on patients hospitalized for conventional pacemaker implantation remains poorly understood.

METHODS: We utilized the 2020 U.S. National Inpatient Sample (NIS) database to evaluate the impact of PEM on the in-hospital outcomes of patients who underwent conventional pacemaker implantation. Patients aged 18 and older were identified by ICD-10 CM and PCS codes. Multivariable survey logistic and linear regression analyses were employed to examine in-hospital outcomes, including in-patient mortality, system-based outcomes, and post-procedural complications.

RESULTS: A total of 108 020 patients were identified with 4315 (3.99%) diagnosed with PEM. The mean age of the cohort …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …

Race And Patient-Physician Communication On Blood Pressure Management: Helping Improve Care, Samar A. Nasser, Ashley Pender, Ayan Ali, Kardie Tobb, Keith C. Ferdinand

Division of Cardiology Faculty Papers

PURPOSE OF REVIEW: To provide an overview of the relationship of race and ethnicity and patient-physician/clinician communication on blood pressure management.

RECENT FINDINGS: The suboptimal interactions experienced by patients from underrepresented racial and ethnic populations may be improved by enriching relationships among clinicians, population health scientists, policymakers, and community members/leaders. Current care communication and policies for managing hypertension appear to be insufficient. Implementing and disseminating effective strategies to efficiently improve the quality of hypertension care and recognize social determinants of health among minoritized populations is intertwined with enhanced communication.

SUMMARY: Approaches such as self-affirmation—encouraging patients to reflect on their strengths …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Tead-Independent Mechanisms Of Yap Function In Cardiomyocyte Cell Cycle Reentry, Bing Xie, Jeffrey Steimle, Vaibhav Deshmukh, Lin Liu, Chang-Ru Tsai, Todd R Heallen, Wyatt Paltzer, Yuka Morikawa, Fansen Meng, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA …