Digital Commons Network^™

Oxytocin Dosing During Trial Of Labor After Cesarean To Minimize The Risk Of Uterine Rupture: A Systematic Review And Meta-Analysis, Pierpaolo Nicolì, Moti Gulersen, Jordan Beacham, Hila Hochler, Alessandra Familiari, Anna Locatelli, Cynthia Abraham, Ettore Cicinelli, Amerigo Vitagliano, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Oxytocin remains the mainstay for induction and for the management of labor arrest during trial of labor after cesarean (TOLAC). Therefore, the clinical question should be not whether to use oxytocin, but how to optimize its administration. This meta-analysis aimed to assess which oxytocin protocol, in terms of initial dose, amount of increase, timing to next increase, and maximum dose, may minimize the risk of uterine rupture (UR) during TOLAC.

DATA SOURCES: PubMed, Embase and Clinicaltrials.gov were searched up to September 21, 2024.

STUDY ELIGIBILITY CRITERIA: Randomized and nonrandomized studies evaluating the association between induction and/or augmentation with oxytocin …

Investigation On The Effects Of Hypoxia-Mimicking Agents In Cancer Progression And Oxidative Stress In Hepatocellular Carcinoma, June Wong Xin Ni

Student Works (2020-2029)

Hypoxia, or oxygen deprivation, is a common pathological feature found in hepatocellular carcinoma (HCC). Hypoxia-inducible factor (HIF) is the master transcription factor of oxygen homeostasis, eliciting a wide range of cellular adaptive responses to either enhance oxygen delivery or reduce oxygen consumption. HIF is primarily regulated by two types of oxygen sensors, the prolyl hydroxylase domain-containing proteins (PHDs) and factor-inhibiting HIF (FIH). In tumours, HIF functions as a double-edged sword whereby it could either promote or hinder tumour progression. This is mainly contributed by the pleiotropic nature of hypoxia and tumour heterogeneity. Recently, there is a growing interest in the …

Accelerated Molecular Aging In Neighborhood Poverty: A Racial/Ethnic Comparison, Jennifer Robinette, Jennifer Smith

Psychology Faculty Articles and Research

In the US, racial/ethnic health disparities are undeniable and partially stem from residing in low SES neighborhoods. Associations between neighborhood SES and health may have some underlying molecular mechanisms reflected in the epigenome. Yet, neighborhood characteristics are not always experienced the same way for all residents, and questions remain regarding whether those most exposed to low SES neighborhoods build greater resilience to, or embody greater harmful and cumulative outcomes from, such neighborhoods. The present study tested the hypothesis that greater neighborhood poverty would relate to accelerated epigenetic aging on the Horvath, Hannum, PhenoAge, and GrimAge clocks, and that these associations …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

Novel Physical And Biological Applications Of Carbon Ion Radiotherapy, Danushka Seneviratne, Prapannajeet Biswal, Sunil Krishnan

The Brown Foundation: Institute of Molecular Medicine

Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it is expected to improve the therapeutic ratio of radiation treatments and enhance treatment outcomes in traditionally radiation-resistant tumor histologies. Despite these unique properties, much remains to be understood regarding the clinical use of CIRT before its full potential can be realized. In this review, we summarize the distinct advantages of CIRT with regard to its physical and …

The Concise Guide To Pharmacology 2025/26: Catalytic Receptors, Stephen P. H. Alexander, Doriano Fabbro, Chloe J. Peach, Alasdair J. Gibb, Eamonn Kelly, Alistair A. Mathie, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Christopher Southan, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Laura Kilpatrick, Doris Koesling, Michaela Kuhn, Birgit Leitinger, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H. H. W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

Work-Related Musculoskeletal Disorders: Epidemiology, Risk Factors, Socioeconomic Impact And Prevention - A Narrative Review, Swarna Radhakrishnan, Harini Ramendran, Priyanga Thirunavukkarasu

Digital Journal of Clinical Medicine

Abstract

Work-related musculoskeletal disorders (WMSDs) represent one of the most pervasive and costly occupational health challenges worldwide. Affecting muscles, tendons, ligaments, nerves, joints, and supporting blood vessels, these conditions arise from a complex interplay of physical, psychosocial, organizational, and individual risk factors present across diverse work environments. From factory floors and construction sites to offices and healthcare settings, WMSDs contribute substantially to pain, disability, reduced productivity, absenteeism, and diminished quality of life. This narrative review synthesizes existing literature on the epidemiology, pathophysiology, risk factors, and socioeconomic impact of WMSDs, with particular attention to high-risk occupational sectors. It further discusses prevention …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Jessica N Vincent, Joy M Schmitz, Scott D Lane

Faculty, Staff and Student Publications

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the …

Exploring The Role Of Astrocyte System Xc– In Excitatory/Inhibitory Balance, Samantha Olivia Sutton

Theses - ALL

Astrocytes play a central role in maintaining excitatory/inhibitory (E/I) balance in the central nervous system by supporting intracellular glutathione (GSH) synthesis and regulating extracellular glutamate. System xc– (Sxc–), an obligate cystine/glutamate antiporter encoded by SLC7a11, couples the import of L-cystine with the export of L-glutamate. It is highly expressed throughout the cortex, hippocampus, striatum, and cerebellum, where its activity provides cystine—the rate-limiting substrate for cysteine-dependent GSH production—and contributes to ambient glutamatergic tone. Although global loss of Sxc– alters seizure threshold and redox homeostasis, whether these effects arise specifically from the loss of astrocytic Sxc– has remained unresolved. This thesis examined …

Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju

Faculty, Staff and Student Publications

No abstract provided.

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie

Faculty, Staff and Student Publications

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7-14 days of age, designated "transitional ages," as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang

Faculty, Staff and Students Publications

Determining tumor-specificity of MHC-bound peptides is crucial for cancer immunotherapy development, yet current methods struggle with class II peptides and non-reference sequences. We introduce PepQueryMHC, an ultra-fast tool that integrates MHC-bound peptide sequences with translated RNA-seq reads for efficient tumor antigen prioritization. We demonstrate its versatility in prioritizing class I and II tumor antigens, mapping the cellular origins of presented peptides, and resolving uncertainties surrounding the prevalence of proteasome-spliced peptides.

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …

Global Prevalence Of Hyperhomocysteinemia Among Adults With Hypertension: A Narrative Review, Wangkheimayum Ashalata Devi Phd Scholar, Dr. Melita Sheilini Associate Professor, Dr. Rinchen Doma Bhutia Assistant Professor, Corresponding Author: Dr.Melita Sheilini, Associate Professor,Department Of Medical-Surgical Nursing, Manipal College Of Nursing, Manipal Academy Of Higher Education, Manipal, Udupi District, Karnataka, India.Contact Number- 8095976561. Email Id: [email protected]

Manipal Journal of Nursing and Health Sciences

Background: Elevated blood homocysteine (Hcy) levels are a hallmark of hyperhomocysteinemia (HHcy), a metabolic disorder that is known to be a risk factor for cardiovascular illnesses. It greatly raises the risk of vascular problems when combined with hypertension (HTN). However, there are few statistics on the prevalence of HHcy in individuals with HTN. Objective: The present review aims to estimate the global prevalence of HHcy among adults with HTN and to highlight regional disparities, associated risk factors, and implications for clinical practice. Method: The comprehensive literature search was conducted using the PubMed and Google Scholar search engines. Studies published in …

Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin

The Brown Foundation: Institute of Molecular Medicine

Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.

Results: A total of 3158 subjects in 1043 …

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …

Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu

Faculty, Staff and Student Publications

Background: Epithelial cell adhesion molecule (EpCAM) is a pleotropic transmembrane glycoprotein comprising an extracellular domain (EpEX), a single transmembrane domain, and an intracellular domain (EpICD). For several types of cancer, high EpCAM expression is associated with tumor progression, metastasis, immune evasion, and overall poor prognosis. A rare but aggressive form of thyroid cancer, anaplastic thyroid cancer (ATC), has a mean survival time of only 3–6 months after diagnosis.

Methods: The levels of EpEX and EpICD cleavage in clinical patient samples was evaluated by using tissue microarray. Capture enzyme-linked immunosorbent assay (ELISA) was conducted to explore the of shedding EpEX and …

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …

Multiple Sclerosis: An Ethnically Diverse Disease With Worldwide Equity Challenges Accessing Care, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) affects approximately 2.9 million people in the world, exerting a significant economic and societal burden. The disease is increasingly identified among populations considered as uncommonly affected. MS is reported in all regions of the World Health Organization (WHO) member states in Africa, the Americas, South-East Asia, Europe, the Eastern Mediterranean and the Western Pacific, affecting all ethnicities while exhibiting substantially variable prevalences. Countries with high MS prevalence and some with moderate frequencies generally have economically better structured healthcare systems. Nevertheless, health disparities in these countries are accentuated by suboptimal accessibility of care for their minorities, immigrants and …