Digital Commons Network^™

Estradiol Mediates Colonic Epithelial Protection In Aged Mice After Stroke And Is Associated With Shifts In The Gut Microbiome, Juneyoung Lee, Pedram Peesh, Victoria Quaicoe, Chunfeng Tan, Anik Banerjee, Patrick Mooz, Bhanu P Ganesh, Joseph Petrosino, Robert M Bryan, Louise D Mccullough, Venugopal Reddy Venna

Faculty, Staff and Student Publications

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young …

Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma, Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford

Faculty, Staff and Student Publications

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can …

A Heritable Iron Memory Enables Decision-Making In Escherichia Coli, Souvik Bhattacharyya, Nabin Bhattarai, Dylan M Pfannenstiel, Brady Wilkins, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This “iron” memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with …

Precision Recruitment And Engagement Of Individuals At Risk For Diabetes And Hypertension In Clinical Trials (Predhict): A Randomized Trial For An E-Persuasive Mobile Application To Inform Decision Making About Clinical Trials, Azizi Seixas, Shannique Richards, Jesse Q Moore, Chigozirim Izeogu, Laronda A Hollimon, Peng Jin, Girardin Jean-Louis

Faculty, Staff and Student Publications

The primary objective of this randomized trial was to test the effectiveness of the PREDHiCT digital application, which provides educational and supportive navigation to increase willingness to participate in a future clinical trial. The second objective was to test whether PREDHiCT increased clinical trial literacy or enhanced psychological facilitators of clinical trial participation, such as altruism. To test these two objectives, we conducted a 1-month remote decentralized trial with 100 participants who either have a personal or family history of cardiometabolic health conditions, such as hypertension, diabetes, and obesity. Results indicated significant changes in altruism (mean: -2.94 vs. 0.83;

Hyperleptinemia Contributes To Antipsychotic Drug-Associated Obesity And Metabolic Disorders, Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Joel K Elmquist, Olivia Osborn, Chen Liu, Philipp E Scherer

Faculty, Staff and Students Publications

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly …

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong

Faculty, Staff and Students Publications

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, …

Prediagnostic Selenium Status, Selenoprotein Gene Variants And Association With Breast Cancer Risk In A European Cohort Study, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Veronika Fedirko, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst, Guri Skeie, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Sandra M Colorado Yohar, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Alicia K Heath, Laure Dossus

Faculty, Staff and Student Publications

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional …

The Role Of Vitamin D In Patients With Inflammatory Bowel Disease Treated With Vedolizumab, Bincy P Abraham, Christopher Fan, Theresa Thurston, Joshua Moskow, Hoda M Malaty

Faculty, Staff and Students Publications

BACKGROUND: Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD.

METHODS: We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis …

Safety And Immunogenicity Of Etvax®, An Oral Inactivated Vaccine Against Enterotoxigenic Escherichia Coli Diarrhoea: A Double-Blinded, Randomized, Placebo-Controlled Trial Amongst Finnish Travellers To Benin, West Africa, Anu Kantele, Marianna Riekkinen, T Sakari Jokiranta, Sari H Pakkanen, Jukka-Pekka Pietilä, Anu Patjas, Mari Eriksson, Tamim Khawaja, Peter Klemets, Kati Marttinen, Heli Siikamäki, Anna Lundgren, Jan Holmgren, Agneta Lissmats, Nils Carlin, Ann-Mari Svennerholm

Faculty and Staff Publications

Background: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.

Methods: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 …

Revisiting The Use Of Normal Saline For Peritoneal Washing In Ovarian Cancer, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing …

Pmca Screening Of Retropharyngeal Lymph Nodes In White-Tailed Deer And Comparisons With Elisa And Ihc, Rebeca Benavente, J Hunter Reed, Mitch Lockwood, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervids. CWD diagnosis is conducted through enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in retropharyngeal lymph nodes. Unfortunately, these techniques have limited sensitivity against the biomarker (CWD-prions). Two in vitro prion amplification techniques, real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have shown promise in detecting CWD-prions in tissues and bodily fluids. Recent studies have demonstrated that RT-QuIC yields similar results compared to ELISA and IHC. Here, we analyzed 1003 retropharyngeal lymph nodes (RPLNs) from Texas white-tailed deer. PMCA detected CWD at a higher rate compared to ELISA/IHC, identified …

Identification Of Cdk1, Pbk, And Chek1 As An Oncogenic Signature In Glioblastoma: A Bioinformatics Approach To Repurpose Dapagliflozin As A Therapeutic Agent, Harold A Chinyama, Li Wei, Ntlotlang Mokgautsi, Bashir Lawal, Alexander T H Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor whose median survival is less than 15 months. The current treatment regimen comprising surgical resectioning, chemotherapy with Temozolomide (TMZ), and adjuvant radiotherapy does not achieve total patient cure. Stem cells' presence and GBM tumor heterogeneity increase their resistance to TMZ, hence the poor overall survival of patients. A dysregulated cell cycle in glioblastoma enhances the rapid progression of GBM by evading senescence or apoptosis through an over-expression of cyclin-dependent kinases and other protein kinases that are the cell cycle's main regulatory proteins. Herein, we identified and validated the …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Identification Of Exosome Protein Panels As Predictive Biomarkers For Non-Small Cell Lung Cancer, Bin Luo, Zujun Que, Xinyi Lu, Dan Qi, Zhi Qiao, Yun Yang, Fangfang Qian, Yi Jiang, Yan Li, Ronghu Ke, Xiaoyun Shen, Hua Xiao, Hegen Li, Erxi Wu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.

Methods: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.

Results: …

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

Faculty, Staff and Student Publications

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …

The Importance Of A Healthy Microbiome In Pregnancy And Infancy And Microbiota Treatment To Reverse Dysbiosis For Improved Health, Herbert L Dupont, Madeleine Mary Hines Salge

Faculty, Staff and Student Publications

BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during …

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

Correlations Between Mental Health, Physical Activity, And Body Composition In American College Students After The Covid-19 Pandemic Lockdown, Luis Torres, Manuela C Caciula, Alin S Tomoiaga, Carmen Gugu-Gramatopol

Faculty, Staff and Student Publications

Restrictions associated with the COVID-19 pandemic had forced American college students to significantly reduce their daily energy expenditure and increase their sedentary behaviors, thus presumably increasing mental health symptoms, decreasing physical activity levels, and enhancing the promotion of unhealthy eating habits. This study aimed to explore the correlations between mental health symptoms, physical activity levels, and body composition in college students in the years following the pandemic, focusing on the lingering effects of lockdown measures. American college students completed pre-existing, well-validated surveys for both mental health (Hospital Anxiety and Depression Scale) and physical activity (International Physical Activity Questionnaire—Long Form). Body …

A Novel Machine-Learning Framework Based On A Hierarchy Of Dispute Models For The Identification Of Fish Species Using Multi-Mode Spectroscopy, Mitchell Sueker, Amirreza Daghighi, Alireza Akhbardeh, Nicholas Mackinnon, Gregory Bearman, Insuck Baek, Chansong Hwang, Jianwei Qin, Amanda M Tabb, Jiahleen B Roungchun, Rosalee S Hellberg, Fartash Vasefi, Moon Kim, Kouhyar Tavakolian, Hossein Kashani Zadeh

Faculty, Staff and Student Publications

Seafood mislabeling rates of approximately 20% have been reported globally. Traditional methods for fish species identification, such as DNA analysis and polymerase chain reaction (PCR), are expensive and time-consuming, and require skilled technicians and specialized equipment. The combination of spectroscopy and machine learning presents a promising approach to overcome these challenges. In our study, we took a comprehensive approach by considering a total of 43 different fish species and employing three modes of spectroscopy: fluorescence (Fluor), and reflectance in the visible near-infrared (VNIR) and short-wave near-infrared (SWIR). To achieve higher accuracies, we developed a novel machine-learning framework, where groups of …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …

A Qualitative Study On Parenting Practices To Sustain Adolescent Health Behaviors In American Indian Families, Christine Hodgson, Dylan Decker, Teresia M O'Connor, Melanie Hingle, Francine C Gachupin

Children’s Nutrition Research Center Staff Publications

American Indian (AI) adolescents who practice healthy behaviors of sleep, nutrition, physical activity, and limited screen time can lower their lifetime risk of diet-sensitive disease. Little is known about how AI parenting practices influence the health behaviors of youth. The objective of this qualitative study was to explore how a group of AI parents of youths at risk of disease influenced their youth’s health behaviors after a family intervention. A secondary objective was to understand the role of AI parents in supporting and sustaining health behavior change in their youths following the intervention. Semi-structured in-depth interviews were conducted with AI …

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …

Associations Between Rest-Activity Rhythms And Liver Function Tests: The Us National Health And Nutrition Examination Survey, 2011-2014, Chris Ho Ching Yeung, Cici Bauer, Qian Xiao

Faculty, Staff and Student Publications

Liver functions are regulated by the circadian rhythm; however, whether a weakened circadian rhythm is associated with impaired liver function is unclear. This study aims to investigate the association of characteristics of rest-activity rhythms with abnormal levels of biomarkers of liver function. Data were obtained from the National Health and Nutrition Examination Survey 2011-2014. Seven rest-activity rhythm parameters were derived from 24 h actigraphy data using the extended cosine model and non-parametric methods. Multiple logistic regression and multiple linear regression models were used to assess the associations between rest-activity rhythm parameters and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase …

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

The Prognostic Role Of Platelet-To-Lymphocyte Ratio In Acute Coronary Syndromes: A Systematic Review And Meta-Analysis, Michal Pruc, Frank William Peacock, Zubaid Rafique, Damian Swieczkowski, Krzysztof Kurek, Monika Tomaszewska, Burak Katipoglu, Maciej Koselak, Basar Cander, Lukasz Szarpak

Faculty, Staff and Students Publications

This study aimed to investigate the potential prognostic role of the platelet-to-lymphocyte (PLR) ratio in patients presenting with suspected acute coronary syndromes (ACS). A systematic search of PubMed Central, Scopus, EMBASE, and the Cochrane Library from conception through 20 August 2023 was conducted. We used odds ratios (OR) as the effect measure with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with a 95% CI for continuous data. If I2 was less than 50% or the p value of the Q tests was less than 0.05, a random synthesis analysis was conducted. Otherwise, a fixed pooled meta-analysis …

Conformational Ensemble-Dependent Lipid Recognition And Segregation By Prenylated Intrinsically Disordered Regions In Small Gtpases, Mussie K Araya, Alemayehu A Gorfe

Faculty, Staff and Student Publications

We studied diverse prenylated intrinsically disordered regions (PIDRs) of Ras and Rho family small GTPases using long timescale atomistic molecular dynamics simulations in an asymmetric model membrane of phosphatidylcholine (PC) and phosphatidylserine (PS) lipids. Here we show that conformational plasticity is a key determinant of lipid sorting by polybasic PIDRs and provide evidence for lipid sorting based on both headgroup and acyl chain structures. We further show that conformational ensemble-based lipid recognition is generalizable to all polybasic PIDRs, and that the sequence outside the polybasic domain (PBD) modulates the conformational plasticity, bilayer adsorption, and interactions of PIDRs with membrane lipids. …

Tfeb And Tfe3 Control Glucose Homeostasis By Regulating Insulin Gene Expression, Adrien Pasquier, Nunzia Pastore, Luca D'Orsi, Rita Colonna, Alessandra Esposito, Veronica Maffia, Rossella De Cegli, Margherita Mutarelli, Susanna Ambrosio, Gennaro Tufano, Antonio Grimaldi, Marcella Cesana, Davide Cacchiarelli, Nathalie Delalleau, Gennaro Napolitano, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

To fulfill their function, pancreatic beta cells require precise nutrient-sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene …

Diverse Clinical Manifestations And Challenges Of Mucormycosis: Insights From Serial Cases, Marisa C Nielsen, Filipe M Cerqueira, Sri Bharathi Kavuri, Caitlin M Raymond, Aeman Muneeb, Andrzej S Kudlicki, Shafaq Tariq, Mingru Liu, Andrew L Routh, Suimin Qiu, Ping Ren

Faculty, Staff and Student Publications

Background: Regulation of mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in aging and nutrition. For example, caloric restriction reduces mTORC1 signaling and extends lifespan, whereas nutrient abundance and obesity increase mTORC1 signaling and reduce lifespan. Skeletal muscle-specific knockout (KO) of DEP domain-containing 5 protein (DEPDC5) results in constitutively active mTORC1 signaling, muscle hypertrophy and an increase in mitochondrial respiratory capacity. The metabolic profile of skeletal muscle, in the setting of hyperactive mTORC1 signaling, is not well known.

Objectives: To determine the metabolomic and lipidomic signature in skeletal muscle from female and male wild-type (WT) and DEPDC5 …