Digital Commons Network^™

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related …

Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A. Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …

Randomized Controlled Trial Of A Novel Lifestyle Intervention Used With Or Without Meal Replacements In Work Sites, Sai Krupa Das, Rachel E Silver, Taylor A Vail, Meghan K Chin, Caroline M Blanchard, Stephanie L Dickinson, Xiwei Chen, Lisa Ceglia, Edward Saltzman, David B Allison, Susan B Roberts

Children’s Nutrition Research Center Staff Publications

Objective: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting.

Methods: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees …

Age And Racial Disparities In The Utilization Of Anticancer, Antihypertension, And Anti-Diabetes Therapies, And In Mortality In A Large Population-Based Cohort Of Older Women With Breast Cancer, Xianglin L Du, Lulu Song

Faculty, Staff and Student Publications

OBJECTIVE: This study examined the receipt of therapies for cancer, hypertension, and diabetes in association with age and racial disparities in mortality among women with breast cancer.

METHODS: This study identified 92,829 women diagnosed with breast cancer at age ≥ 65 years in 2007-2015 with follow-up to 2016 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database.

RESULTS: There were substantial age and racial disparities in the prevalence of hypertension and diabetes, which was higher in women ≥ 75 (86.3% and 32.0%) than younger women 65-74 (72.8% and 29.3%), and the highest in Black women (91.1% and 49.1%), followed …

Racial And Ethnic Disparities In Early-Onset Colorectal Cancer Survival, Timothy A Zaki, Peter S Liang, Folasade P May, Caitlin C Murphy

Faculty, Staff and Student Publications

BACKGROUND: Young adults diagnosed with colorectal cancer (CRC) comprise a growing, yet understudied, patient population. We estimated 5-year relative survival of early-onset CRC and examined disparities in survival by race-ethnicity in a population-based sample.

METHODS: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries to identify patients diagnosed with early-onset CRC (20-49 years of age) between January 1, 1992, and December 31, 2013. For each racial-ethnic group, we estimated 5-year relative survival, overall and by sex, tumor site, and stage at diagnosis. to illustrate temporal trends, we compared 5-year relative survival in 1992-2002 vs …

Relationships Between Urinary Metals And Diabetes Traits Among Mexican Americans In Starr County, Texas, Usa, Margaret C Weiss, Yu-Hsuan Shih, Molly Scannell Bryan, Brian P Jackson, David Aguilar, Craig L Hanis, Maria Argos, Robert M Sargis

Faculty, Staff and Student Publications

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of …

Reduced Spag17 Expression In Systemic Sclerosis Triggers Myofibroblast Transition And Drives Fibrosis, Paulene Sapao, Elisha D O Roberson, Bo Shi, Shervin Assassi, Brian Skaug, Fred Lee, Alexandra Naba, Bethany E Perez White, Carlos Córdova-Fletes, Pei-Suen Tsou, Amr H Sawalha, Johann E Gudjonsson, Feiyang Ma, Priyanka Verma, Dibyendu Bhattacharyya, Mary Carns, Jerome F Strauss, Delphine Sicard, Daniel J Tschumperlin, Melissa I Champer, Paul J Campagnola, Maria E Teves, John Varga

Faculty, Staff and Student Publications

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased …

Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong

Faculty, Staff and Student Publications

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today's obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year.

METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction …

Cross-Sectional And Prospective Associations Of Rest-Activity Rhythms With Body Mass Index In Older Men: A Novel Analysis Using Harmonic Hidden Markov Models, Brian Heckler, Miryoung Lee, Katie Stone, Cici Bauer, Qian Xiao

Faculty, Staff and Student Publications

Growing evidence supports a role for rest-activity rhythms (RARs) in metabolic health. Epidemiological studies in adolescents and young adults showed that RAR characteristics consistent with weakened rhythmicity were associated with obesity. However, studies in older adults are lacking. The objective of this study was to examine the cross-sectional and prospective associations between RAR and obesity in older men using the Harmonic Hidden Markov Model (HHMM), a novel analytical approach with several advantages over conventional methods for characterizing RAR. The analysis included nearly 3,000 participants in the Osteoporotic Fractures in Men study with 5-day 24-h actigraphy data. The strength of RAR …

Antibody Therapies For The Treatment Of Acute Myeloid Leukemia: Exploring Current And Emerging Therapeutic Targets, Joshua W Morse, Margarita Rios, John Ye, Adan Rios, Cheng Cheng Zhang, Naval G Daver, Courtney D Dinardo, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

INTRODUCTION: Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients.

AREAS COVERED: In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each …

Optimizing Teaching Effectiveness In Dental Education For A New Generation Of Learners, Christopher J Walinski, Joe C Ontiveros, Fei Liu, Geralyn Crain, Saynur Vardar-Sengul

Faculty, Staff and Student Publications

Purpose: Today's dental students, Generation Z (Gen Z), are said to learn differently than those of previous generations. As generations of dental students vary, our teaching styles must keep up with unique and changing groups of individuals.

Methods: This article discusses learner-focused teaching methods including techniques that address the characteristics of Gen Z learners. Blended learning methods that combine online media with traditional face-to-face sessions, team-based learning, and a flipped classroom format have previously been suggested as ways to increase learning effectiveness and student satisfaction.

Results: In this paper, the characteristics and preferences of Gen Z students are described along …

Sexual Behaviors And Human Papillomavirus Vaccination In A Heterosexually Active Adult Population At Increased Risk For Hiv Infection, Trisha L Amboree, Paige P Wermuth, Jane R Montealegre, Kayo Fujimoto, Osaro Mgbere, Charles Darkoh

Faculty, Staff and Student Publications

Human papillomavirus (HPV) is the most common sexually acquired infection in the US. Vaccination is effective against infection with high-risk HPV strains, yet HPV vaccine coverage is lower in the US than the national target. This study aimed to determine the relationship between sexual behaviors and HPV vaccination in a heterosexually active population at increased risk for HIV infection. Data from 380 participants aged 18-45 years obtained from the National HIV Behavioral Surveillance system increased risk heterosexuals cycle 5 (2019) in Houston, Texas, was analyzed. RDS-Analyst was used to generate population-based descriptive statistics. Modified Poisson regression models clustered on recruitment …

Ampk Regulates Homeostasis Of Invasion And Viability In Trophoblasts By Redirecting Glucose Metabolism: Implications For Pre-Eclampsia, Ping Xu, Yangxi Zheng, Jiujiang Liao, Mingyu Hu, Yike Yang, Baozhen Zhang, Mark D Kilby, Huijia Fu, Yamin Liu, Fumei Zhang, Liling Xiong, Xiyao Liu, Huili Jin, Yue Wu, Jiayu Huang, Tingli Han, Li Wen, Rufei Gao, Yong Fu, Xiujun Fan, Hongbo Qi, Philip N Baker, Chao Tong

Faculty, Staff and Student Publications

Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS). Trophoblast-specific AMPKα1-deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle-delivered A769662. Trophoblast glucose uptake was measured by 2-NBDG and 2-deoxy-d-[

Adjuvant 5-Fluorouracil/Leucovorin, Capecitabine, And Oxaliplatin-Related Regimens For Stage Ii/Iii Colon Cancer Patients 66 Years Or Older, Emily Jones, Zhigang Duan, Thinh T Nguyen, Sharon H Giordano, Hui Zhao

Faculty, Staff and Student Publications

Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FU/LV), capecitabine, and adding oxaliplatin to 5-FU/LV or capecitabine (FLOX/OX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used …

Superficial Low-Grade Fibromyxoid Sarcoma, Shira Ronen, Jennifer S Ko, Brian P Rubin, Scott E Kilpatrick, Wei-Lien Wang, Alexander J Lazar, John R Goldblum, Steven D Billings

Faculty, Staff and Student Publications

Background: Low-grade fibromyxoid sarcoma (LGFMS) typically involves deep soft tissue (beneath the fascia) of the proximal extremities and trunk. Long-term follow-up has shown a high rate of local recurrence, metastasis, and death. To the best of our knowledge, there is only one previous large series focusing on superficial LGFMS suggesting superficial tumors are disproportionately more common in children and may have a better prognosis. Our study's primary goals are to confirm these findings and increase general awareness that LGFMS may arise in superficial soft tissue.

Methods: We retrieved our cases of superficial LGFMS diagnosed between 2008 and 2020. Available slides …

The Influence Of Posttraumatic Stress Disorder Treatment On Anxiety Sensitivity: Impact Of Prolonged Exposure, Sertraline, And Their Combination, Matthew T Luciano, Sonya B Norman, Carolyn B Allard, Ron Acierno, Naomi M Simon, Kristin L Szuhany, Amanda W Baker, Murray B Stein, Brian Martis, Peter W Tuerk, Sheila A M Rauch, Progress Study Team

Faculty, Staff and Student Publications

Trauma-informed beliefs often decrease during posttraumatic stress disorder (PTSD) treatment. This may also extend to anxiety sensitivity (AS), defined as a fear of anxiety-related sensations and beliefs that anxiety is dangerous and/or intolerable. However, little is known about how AS changes during exposure-based and psychopharmacological PTSD treatments. Further, high AS may be a risk factor for diminished PTSD symptom improvement and increased treatment dropout. To better understand how AS impacts and is impacted by PTSD treatment, we conducted a secondary analysis of a randomized clinical trial with a sample of 223 veterans (87.0% male, 57.5% White) with PTSD from four …

Base Editing Correction Of Hypertrophic Cardiomyopathy In Human Cardiomyocytes And Humanized Mice, Andreas C Chai, Miao Cui, Francesco Chemello, Hui Li, Kenian Chen, Wei Tan, Ayhan Atmanli, John R Mcanally, Yu Zhang, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N Olson

Faculty, Staff and Student Publications

The most common form of genetic heart disease is hypertrophic cardiomyopathy (HCM), which is caused by variants in cardiac sarcomeric genes and leads to abnormal heart muscle thickening. Complications of HCM include heart failure, arrhythmia and sudden cardiac death. The dominant-negative c.1208G>A (p.R403Q) pathogenic variant (PV) in β-myosin (MYH7) is a common and well-studied PV that leads to increased cardiac contractility and HCM onset. In this study we identify an adenine base editor and single-guide RNA system that can efficiently correct this human PV with minimal bystander editing and off-target editing at selected sites. We show that delivery of …

Pkr Induces Tgf-Β And Limits Oncolytic Immune Therapy, Bangxing Hong, Upasana Sahu, Matthew P Mullarkey, Evan Hong, Guangsheng Pei, Yuanqing Yan, Yoshihiro Otani, Yeshavanth Banasavadi-Siddegowda, Huihui Fan, Zhongming Zhao, Jianhua Yu, Michael A Caligiuri, Balveen Kaur

Faculty, Staff and Student Publications

BACKGROUND: Mammalian cells have developed multiple intracellular mechanisms to defend against viral infections. These include RNA-activated protein kinase (PKR), cyclic GMP-AMP synthase and stimulation of interferon genes (cGAS-STING) and toll-like receptor-myeloid differentiation primary response 88 (TLR-MyD88). Among these, we identified that PKR presents the most formidable barrier to oncolytic herpes simplex virus (oHSV) replication in vitro.

METHODS: To elucidate the impact of PKR on host responses to oncolytic therapy, we generated a novel oncolytic virus (oHSV-shPKR) which disables tumor intrinsic PKR signaling in infected tumor cells.

RESULTS: As anticipated, oHSV-shPKR resulted in suppression of innate antiviral immunity and improves virus …

Phase Ii Trial Of Weekly Erlotinib Dosing To Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis, N Jewel Samadder, Nathan Foster, Ryan P Mcmurray, Carol A Burke, Elena Stoffel, Priyanka Kanth, Rohit Das, Marcia Cruz-Correa, E Vilar, Gautam Mankaney, Navtej Buttar, Selvi Thirumurthi, Danielle K Turgeon, Michael Sossenheimer, Michelle Westover, Ellen Richmond, Asad Umar, Gary Della'zanna, Luz M Rodriguez, Eva Szabo, David Zahrieh, Paul J Limburg

Faculty, Staff and Student Publications

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Design, setting and participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres.

Exposures: Participants self-administered 350 mg of erlotinib …

Recruitment In Acute Stroke Trials: Challenges And Potential Solutions, Joseph P Broderick, Yasmin N Aziz, Opeolu M Adeoye, James C Grotta, Andrew M Naidech, Andrew D Barreto, Colin P Derdeyn, Heidi J Sucharew, Jordan J Elm, Pooja Khatri

Faculty, Staff and Student Publications

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of …

Mitochondria-Containing Extracellular Vesicles (Ev) Reduce Mouse Brain Infarct Sizes And Ev/Hsp27 Protect Ischemic Brain Endothelial Cultures, Kandarp M Dave, Donna B Stolz, Venugopal R Venna, Victoria A Quaicoe, Michael E Maniskas, Michael John Reynolds, Riyan Babidhan, Duncan X Dobbins, Maura N Farinelli, Abigail Sullivan, Tarun N Bhatia, Hannah Yankello, Rohan Reddy, Younsoo Bae, Rehana K Leak, Sruti S Shiva, Louise D Mccullough, Devika S Manickam

Faculty, Staff and Student Publications

Ischemic stroke causes brain endothelial cell (BEC) death and damages tight junction integrity of the blood-brain barrier (BBB). We harnessed the innate mitochondrial load of BEC-derived extracellular vesicles (EVs) and utilized mixtures of EV/exogenous 27 kDa heat shock protein (HSP27) as a one-two punch strategy to increase BEC survival (via EV mitochondria) and preserve their tight junction integrity (via HSP27 effects). We demonstrated that the medium-to-large (m/lEV) but not small EVs (sEV) transferred their mitochondrial load, that subsequently colocalized with the mitochondrial network of the recipient primary human BECs. Recipient BECs treated with m/lEVs showed increased relative ATP levels and …

Assessment Of Symptom, Disability, And Financial Trajectories In Patients Hospitalized For Covid-19 At 6 Months, Andrew J Admon, Theodore J Iwashyna, Lee A Kamphuis, Stephanie J Gundel, Sarina K Sahetya, Ithan D Peltan, Steven Y Chang, Jin H Han, Kelly C Vranas, Kirby P Mayer, Aluko A Hope, Sarah E Jolley, Ellen Caldwell, Max L Monahan, Katrina Hauschildt, Samuel M Brown, Neil R Aggarwal, B Taylor Thompson, Catherine L Hough

Faculty, Staff and Student Publications

IMPORTANCE: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited.

OBJECTIVE: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization.

DESIGN, SETTING, AND PARTICIPANTS: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization …

American Radium Society (Ars) Appropriate Use Criteria (Auc) For Extrahepatic Cholangiocarcinoma, Leila T Tchelebi, Krishan R Jethwa, Anna T Levy, Christopher J Anker, Timothy Kennedy, Elliot Grodstein, Christopher L Hallemeier, Salma K Jabbour, Ed Kim, Rachit Kumar, Percy Lee, William Small, Vonetta M Williams, Navesh Sharma, Suzanne Russo

Faculty, Staff and Student Publications

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic …

Hyaluronan In The Pathogenesis Of Acute And Post-Acute Covid-19 Infection, Henry W Barnes, Sally Demirdjian, Naomi L Haddock, Gernot Kaber, Hunter A Martinez, Nadine Nagy, Harry Karmouty-Quintana, Paul L Bollyky

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. …

Retrospective Evaluation Of The Role Of Gemcitabine-Docetaxel In Well-Differentiated And Dedifferentiated Liposarcoma, Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei-Lien Wang, Jeffrey M Cloutier, Elise F Nassif, Emily Z Keung, Christina L Roland, Barry Feig, Dejka Araujo, Robert S Benjamin, Anthony P Conley, John A Livingston, Joseph Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah

Faculty, Staff and Student Publications

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS.

METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups.

RESULTS: Sixty-five WDLPS/DDLPS patients …

Automatic Diagnosis Of Late-Life Depression By 3d Convolutional Neural Networks And Cross-Sample Entropy Analysis From Resting-State Fmri, Chemin Lin, Shwu-Hua Lee, Chih-Mao Huang, Guan-Yen Chen, Wei Chang, Ho-Ling Liu, Shu-Hang Ng, Tatia Mei-Chun Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Resting-state fMRI has been widely used in investigating the pathophysiology of late-life depression (LLD). Unlike the conventional linear approach, cross-sample entropy (CSE) analysis shows the nonlinear property in fMRI signals between brain regions. Moreover, recent advances in deep learning, such as convolutional neural networks (CNNs), provide a timely application for understanding LLD. Accurate and prompt diagnosis is essential in LLD; hence, this study aimed to combine CNN and CSE analysis to discriminate LLD patients and non-depressed comparison older adults based on brain resting-state fMRI signals. Seventy-seven older adults, including 49 patients and 28 comparison older adults, were included for fMRI …

Clinical Features Associated With Outcomes And Biomarker Analysis Of Dabrafenib Plus Trametinib Treatment In Patients With Braf-Mutant Melanoma Brain Metastases, James S Wilmott, Hussein Tawbi, Johnathan A Engh, Nduka M Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A Vergara, Hansol Lee, Peter A Johansson, Peter M Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H Butterfield, Richard A Scolyer, John M Kirkwood, Georgina V Long, Michael A Davies

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).

PATIENTS AND METHODS: Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate …

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, Fuu-Jen Tsai

Faculty, Staff and Student Publications

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The …