Medical Sciences Commons^™

Global Trends And Forecast Of Cardiovascular Diseases, Cancer, And Shared Risk Factors: Insights From The Gbd 2021, Chieh Y Koo, Bryan Chong, Jayanth Jayabaskaran, Srinithy Nagarajan, Silingga M Jauhari, Yiming Chen, Li L Tan, Anurag Mehta, Muhammad S Khan, Mark Muthiah, Derek Hausenloy, A M Richards, Dennis T Ko, Christian D Mallen, Eric A Secemsky, Mark Y Chan, Paaladinesh Thavendiranathan, Nicholas W S Chew, Mamas A Mamas

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) and cancer share multiple risk factors and are the leading causes of morbidity and death worldwide. This study aims to examine historical and projected trends of the combined CVD-cancer global estimates and their shared risk factors.

Methods: Death and disability-adjusted life years (DALYs) associated with CVDs, cancers, and their risk factors were obtained from the GBD (Global Burden of Disease) 2021 study. Historical estimates from 1990 to 2021 and forecast data from 2025 to 2050 were examined across age groups, regions, sociodemographic index, and sex.

Results: In 2021, CVD-cancer resulted in age-standardized DALY rates of 8009 …

Timing And Mode Of Death Following Treatment Of Neonatal Symptomatic Tetralogy Of Fallot, Sara M Trucco, Yun Zhang, Andrew C Glatz, Michael L O'Byrne, Christopher J Petit, Athar M Qureshi, Jeffrey D Zampi, Shabana Shahanavaz, George T Nicholson, Allen Ligon, Jennifer C Romano, Shiraz A Maskatia, Jeffery J Meadows, Christopher Mascio, Jay Patel, Kathryn Stack, Asaad G Beshish, Mark Law, Sarosh P Batlivala, Jeannette Wong-Siegel, Kristal Hock, Sarah Speed, Hala Khan, Disha Goel, Courtney Mccracken, Bryan H Goldstein

Faculty, Staff and Students Publications

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, using a staged or primary repair strategy. Postprocedural mortality risk within this group is considerable. The mode of death and associated factors have been inadequately defined in early childhood mortality following treatment of sTOF. This study aims to describe the timing, cause, and associated risk factors of postprocedural death in infants with sTOF.

Methods: Neonates with sTOF who had an initial intervention from 2005 to 2017 at 9 centers of the Congenital Cardiac Research Collaborative were reviewed. Among nonsurvivors, details regarding timing, cause of death, and last …

Disparate Leukemia Mutations Converge On Nuclear Phase-Separated Condensates, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting …

Serum Response Factor Is Essential For Endometrial Function And Prevention Of Inflammatory Fibrosis, Ryan M Marquardt, Sara A Grimm, San-Pin Wu, Peter F Lais, Shu-Yun Li, Xin Xu, Erin Smithberger, David Cunefare, Charan Ganta, David Olson, Eunhee M Jeong, Jae-Wook Jeong, Bruce A Lessey, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Pregnancy requires a supportive uterine environment facilitated by steroid hormone–regulated differentiation of endometrial stromal fibroblasts into decidual cells and tight control of inflammation. Serum response factor (SRF) is a widely expressed transcription factor essential for mesenchymal cell growth and differentiation with noted roles in hormonal regulation of muscle tissues but little characterization in reproductive organs. Here, we reveal that endometrial SRF is dysregulated in human endometriosis and is critical for female reproductive success in mice through regulation of endometrial stromal and epithelial cells. Immunohistochemical analysis identified decreased endometrial SRF expression in infertile endometriosis patient tissues. RNAi-based SRF knockdown in human …

Assessing The Impact Of A Semi-Structured Intraoperative Anaesthesia Handoff Cognitive Aid On Surgical Patient Outcomes: Study Protocol For A Cluster Randomised Trial, Aubrey Samost-Williams, Charles E Green, Lillian S Kao, Srikanth Sridhar, Daniel I Sessler, Alparslan Turan, Eric J Thomas

Faculty, Staff and Student Publications

Introduction: Intraoperative anaesthesia handoffs represent a risk point in the care of surgical patients. Although often necessary to prevent fatigue, improve vigilance and optimise operational efficiency, critical information can be lost, potentially leading to postoperative complications. Structured handoffs can increase the transfer of knowledge during intraoperative anaesthesia handoffs, improving their quality. We therefore propose to test the primary hypothesis that a semi-structured intraoperative anaesthesia handoff cognitive aid reduces the number of serious 30-day complications in surgical patients.

Methods and analysis: We will enrol adults having non-cardiac surgery who are scheduled to have an intraoperative anaesthesia handoff for operational reasons. We …

Therapeutic Potential Of Prmt1 As A Critical Survival Dependency Target In Multiple Myeloma, Tabish Hussain, Sharad Awasthi, Farid Shahid, S Stephen Yi, Nidhi Sahni, C Marcelo Aldaz

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a neoplasm of antibody-producing plasma cells and is the second most prevalent hematological malignancy worldwide. Development of drug resistance and disease relapse significantly impede the success of MM treatment, highlighting the critical need to discover novel therapeutic targets. In a custom CRISPR/Cas9 screen targeting 197 DNA damage response-related genes, Protein Arginine N-Methyltransferase 1 (PRMT1) emerged as a top hit, revealing it as a potential therapeutic vulnerability and survival dependency in MM cells. PRMT1, a major Type I PRMT enzyme, catalyzes the asymmetric transfer of methyl groups to arginine residues, influencing gene transcription and protein function through …

Effects Of Combining Traditional East Asian And Conventional Western Medicine On Acute Stroke Outcomes, Dong-Seok Gwak, Jong-Sik Lee, Dawid Schellingerhout, Jinyong Chung, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Hee-Joon Bae, Mikyung Kim, Dong-Jun Choi, Dong-Eog Kim

Faculty, Staff and Student Publications

Background: Traditional East Asian medicine (TM) is widely used in Korea and other East Asian countries. However, the effects of TM treatment on acute ischemic stroke (AIS) outcomes remain unclear, as previous studies lacked a sufficient sample size, a consecutive series design, or a prospective outcome capture approach. We aimed to investigate whether combining TM with conventional Western medicine (CM) treatments (C+TM) leads to better outcomes after AIS, relative to CM treatment alone.

Methods: We retrospectively analyzed 2157 consecutive patients with AIS from a prospectively collected registry (2011-2021) at our center and compared the CM and C+TM groups in terms …

Pregnancy Outcomes In Women With Heritable Thoracic Aortic Disease: Data From The Eorp Esc Registry Of Pregnancy And Cardiac Disease (Ropac) Iii, Puck N J Peters, Johanna A Van Der Zande, Julie De Backer, Guillaume Jondeau, Osama Ahmad, Marjorie Richardson, Francesca M Comoglio, Heleen Van Der Zwaan, Siddharth K Prakash, Christina Christersson, Karishma P Ramlakhan, Roger Hall, Mark R Johnson, Jolien W Roos-Hesselink, Ropac Investigators

Faculty, Staff and Student Publications

Aims: The risk of pregnancy in women with heritable thoracic aortic disease (HTAD) is estimated to be high, but supporting data are scarce. The aim of this study is to prospectively investigate pregnancy outcomes to improve patient management and care.

Methods and results: The Registry of Pregnancy and Cardiac disease (ROPAC) III is a prospective global registry including pregnant women with known aortic pathology between 2018 and 2023. Cardiac, obstetric and fetal outcomes, beta-blocker use, and the impact of breastfeeding were investigated. Additionally, changes in aortic diameters were assessed. In total, 176 pregnancies in 170 women (mean age 32 years, …

Elucidating The Relationship Between Water Quality And Antibiotic Resistance Of Rainwater Microbes Across Western Humboldt County, Theo P. Murphy, Eve Wendley, Justice Laskowski, Tyler Paredes

Humboldt Journal of Microbiology

Limited studies have been conducted regarding the fecal contamination and microbial dispersal through rainwater, with no known studies investigating the potential connection between antibiotic resistant microbes and water quality in rainwater. This study seeks to identify the presence of a correlation between water quality and incidence of antibiotic resistance in rainwater microbes. We hypothesize that there will be a correlation between these two variables. We additionally anticipate a high incidence of fecal contamination across rural and urban collection sites alike, with fecal contamination being more prevalent in rural areas than urban locals. To determine water quality, we measured the concentration …

Accidental Daily Dosing: Severe Methotrexate Toxicity In A Patient With Rheumatoid Arthritis, Sidra Memon, Kavitha Vemuri, Syed Uzair Mahmood, Darshit Patel

Advances in Clinical Medical Research and Healthcare Delivery

This case highlights a crucial complication of oral methotrexate therapy: toxicity due to dosing errors. A patient’s daily dosing regimen, instead of the intended weekly schedule, led to a significantly excessive cumulative dose of methotrexate over a short period, resulting in severe hematologic and mucosal toxicity. This underscores the importance of clear patient education and vigilant prescription practices to prevent such errors.

Giant Cell Arteritis After Mrna Covid Vaccines: Concerning Or A False Alarm?-A Retrospective Cohort Study, Syed M. F. Zabiullah, Rutwik Pradeep Sharma, Roshan Subedi, Viqarunnisa Faaiza Zahid, Yasir Loai, Sarathlal Mannumbethlal, Aatifa Aatifa

Advances in Clinical Medical Research and Healthcare Delivery

Background: The coronavirus disease (COVID-19) pandemic led to the first large-scale rapid deployment of novel messenger RNA (mRNA) vaccines. Although the effectiveness and safety of these vaccines were rigorously studied, post-vaccination adverse events such as giant cell arteritis (GCA) continue to be reported. More than two hundred and sixty three cases of new-onset GCA occurring after mRNA vaccine administration are listed in the Vaccine Adverse Events Reporting System as of October 2024. We aimed to explore the incidence of GCA after mRNA vaccines among patients in our health system and study their characteristics and outcomes.

Methods: We conducted a …

Intranasal Delivery Of Extracellular Vesicles Derived From Human Bone Marrow Mesenchymal Stem Cells Dampens Neuroinflammation And Ameliorates Motor Deficits In A Mouse Model Of Cortical Stroke, Saviana Antonella Barbati, Chiara D'Amelio, Chiara Feroleto, Marta Morotti, Ida Nifo Sarrapochiello, Francesca Natale, Domenica Donatella Li Puma, Yolanda Gomez-Galvez, Elena Blanco-Suarez, Lorraine Iacovitti, Lucia Leone, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi

Department of Neuroscience Faculty Papers

Early treatment of ischemic stroke can significantly reduce disability and mortality rates. Stem cell-derived extracellular vesicles (EVs) have shown potential as therapeutics for neurological disorders. This study explored whether intranasal administration of EVs from human bone marrow mesenchymal stem cells (BM-MSCs) enhances forelimb motor function recovery in a mouse model of motor cortex stroke and investigated their mechanism of action, focusing on neuroinflammation. C57BL/6JRj mice received EV treatment of 0.1 × 10⁹ EVs per dose per day, 48 h post-stroke and twice weekly for four weeks. EV-treated mice showed significant improvement in forelimb deficits, as evaluated using a series …

Intouch Week Of November 3, 2025, New York Medical College

InTouch

• NYMC Expands Recreational Facilities with New Multi-Sport Courts
• October 22 is Proclaimed New York Medical College Day
• BioInc@NYMC Welcomes Applied Biological Laboratories
• A Legacy of Giving: Endowed Scholarships at NYMC
• TCDM Students Present at the Academy of Laser Dentistry Annual Conference
• TCDM Walks for Wishes
• Alumni Spotlight: Odaelys Pollard, Ph.D. '15, Champions STEM and Empowers Future Scientists

Genomic Profiling Of Intraocular Leiomyomas Reveals Recurrent Copy Number Alterations, Vivian Tang, Yubai Chou, Cuyan Demirkesen, Michele M. Bloomer, Joseph B. Crawford, Ahmet M. Sarici, Carol L. Shields, Ralph C. Eagle Jr., Codrin E. Iacob, Walter P. Devine, Tatyana Milman, Melike Pekmezci

Wills Eye Hospital Papers

PURPOSE: Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

METHODS: We identified eight patients diagnosed with intraocular leiomyoma and performed targeted next-generation sequencing, whole transcriptome RNA sequencing, and chromosomal copy number analysis on those with …

Human Kallikrein 2: A Novel Lineage-Specific Surface Target In Prostate Cancer, Fei Shen, Ryan Smith, Theresa Mcdevitt, Krista Menard, Shaozhou Tian, Gerald Chu, Ruchi Chaudhary, Jennifer Mccann, Halley Oyer, Sherry C. Wang, Steven Max, Peter Francis, William K. Kelly, Charles G. Drake

Kimmel Cancer Center Faculty Papers

PURPOSE: Targeted therapies for metastatic prostate cancer are limited, highlighting the need for novel drug targets and mechanisms of action (MoA). Human kallikrein 2 (KLK2) is a prostate-specific antigen expressed across the prostate cancer disease continuum. However, it was not recognized as a therapeutic target for prostate cancer in the past due to limited evidence of its cell surface expression. In this study, we systematically characterized KLK2 expression in prostate cancer, confirmed its cell surface expression, and demonstrated the preclinical efficacy of three KLK2-targeting therapeutics with distinct MoA.

EXPERIMENTAL DESIGN: The KLK2 expression profile in different stages of prostate cancer …

A Clinical Practice Guideline For The Management Of Pregnancy Alloimmunized To Red Blood Cell Antigens\, Kenneth J Moise, Kara B Markham, Philip C Spinella, Molly R Sherwood, Karen A Robinson, Lisa M Wilson, Jay Malone, Jimmy Espinoza, Donna Dizon-Townson, Laura Mercer, Russell Miller, Leonardo Pereira, Anthony Sciscione, Alireza A Shamshirsaz, Kathryn Shanahan, Saul Snowise, Thomas Trevett, Juan M González Vélez, Bethany Weathersby

Faculty, Staff and Student Publications

Importance: Red blood cell alloimmunization is typically associated with the transplacental transfer of incompatible fetal red blood cells into maternal circulation. Subsequent pregnancies can be affected by fetal anemia, hydrops fetalis, and perinatal death. Most cases of Rhesus D (RhD) alloimmunization due to pregnancy can be prevented by the proper administration of Rhesus immune globulin. However, an emerging practice of using low-titer, O, RhD-positive whole blood (LTOWB) in cases of life-threatening hemorrhage has the potential to increase the exposure of the female population to a new source of incompatible red blood cells.

Objective: To establish recommendations for the management of …

A Multi-National Cross-Sectional Exploration Of Rehabilitation Services For Children And Young People Following Brain Injury In Low And Middle Income Countries, Mark A Linden, Leigh Schrieff-Brown, Linda Ewing-Cobbs, R A Leonard, Rajendra Prasad, Juan Carlos Arango-Lasprilla, Sandra Strazzer, Lucia Braga, Consuelo Reyes Payeras, Kim C Davis, Lisa Kalungwana-Mambwe, Flavia Dorrego, Mathilde Chevignard

Faculty, Staff and Student Publications

Background: Brain injury (BI) is the largest cause of mortality and morbidity among children and can lead to significant cognitive, social, emotional and behavioural deficits. There has been an absence of research examining the availability of rehabilitation services for affected children and young people in low and middle income countries (LMICs). This study therefore investigated current rehabilitation provision in LMICs for children and young people with BI.

Methods: An online survey was developed which collected data on funding support for rehabilitation, causes of BI and access to services. The survey was distributed to healthcare professionals known to members of the …

Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. This study evaluated the individual and combined effects of ethanol, sugars, and saturated/monounsaturated fats on hepatocyte lipid metabolism, oxidative stress, and mitochondrial function using a 3D human HepaRG spheroid model. HepaRG spheroids were treated with ethanol (50 mm), sugar (glucose and fructose), and fatty acids alone or in combination for 10 d. The combination of ethanol (E) and metabolic (sugar and fat, SF) stressors (ESF) synergistically increased triglyceride content …

Developing Optogenetic Approaches To Study Ca2+ Signaling Processes, Tatsuki Nonomura, Xiaoxuan Liu, Megan Chiu, Zhi Tan, Tien-Hung Lan, Yubin Zhou

Faculty, Staff and Students Publications

Calcium ions (Ca2+) are essential second messengers intimately implicated in a variety of biological processes, ranging from short-term events such as muscle contraction to long-term effects like gene expression. Dysregulated Ca2+ signaling can disrupt cellular function and contribute to the development of various human diseases, including developmental, neurological, immunoinflammatory, metabolic, and cardiovascular disorders. To study the mechanisms and biological consequences of Ca2+ signaling, optogenetic approaches have proven invaluable, as they offer exceptional spatiotemporal resolution compared to traditional methods. Recent progress in non-opsin-based optogenetics, particularly those engineered from Ca2+ release–activated Ca2+ (CRAC) channels, has substantially advanced our understanding of Ca2+ signaling …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

Integrative Proteogenomics And Forward Genetics Reveal A Novel Mitotic Vulnerability In Triple-Negative Breast Cancer, Nicholas J Neill, Shankha Satpathy, Karsten Krug, Jitendra K Meena, Nivetha Ramesh Babu, Cheyenne Calderon, Desmon Reed, Marcus J Weber, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Meenakshi Anurag, Kimberly R Holloway, Chen Huang, Suhas Vasaikar, Maria F Cardenas, Beom-Jun Kim, Doug W Chan, Shayan C Avanessian, Siddhartha Tyagi, Mayra Orellana, Sufeng Mao, Heyuan Li, Fade Gong, Sarah J Kurley, Kristen L Meerbrey, Calla M Olson, Amritha Nair, Tingting Sun, Hsiang-Ching Chung, Elizabeth A Bowling, Jarey H Wang, Pengju Zhang, Peng Xiao, Duxiao Yang, Fabio Stossi, Mei-Yin C Polley, Alexander B Saltzman, Filip Mundt, D R Mani, Michael A Gillette, Susan G Hilsenbeck, George Miles, Carolina Gutierrez, C Kent Osborne, Charles Y Lin, Nathanael S Gray, Jinpeng Sun, David A Wheeler, Charles M Perou, Anna Malovannaya, Michael T Lewis, Bing Zhang, Matthew J Ellis, Steven A Carr, Thomas F Westbrook

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent …

Therapeutic Radiation Drives Leptomeningeal Dissemination Of Medulloblastoma Through An Innate Immune Process, Carolina Nör, Kaitlin Kharas, Alex Rasnitsyn, Maria C Vladoiu, Nam Woo Cho, Jacob S Young, Felipe Nör, Ncedile Mankahla, Joonas Haapasalo, Kristiina Nordfors, Sara Rapic, Patryk Skowron, Raúl A Suárez, Alexander T Bahcheli, Oliver Ocsenas, Xin Chen, Shahrzad Bahrampour, Ali Momin, Lakshmikirupa Sundaresan, Winnie Ong, Liam D Hendrikse, Namal Abeysundara, Kyle Juraschka, Michelle Ly, Jonelle G Pallota, Tajana Douglas, Ning Huang, Hao Wang, Esta Mak, Lei Qin, Jessica Liu, Lily Shen, Betty Luu, Alex Manno, Sachin A Kumar, Laura K Donovan, Vernon Fong, Cory Richman, Craig Daniels, Livia Garzia, Jeremy N Rich, Cynthia Hawkins, Xiaochong Wu, Ralph Dacosta, Jüri Reimand, Xi Huang, Vijay Ramaswamy, David R Raleigh, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the most important source of morbidity and mortality for medulloblastoma patients. Radiation of the entire brain is highly effective in the treatment and/or prevention of medulloblastoma leptomeningeal metastases. Infants treated on clinical trials with focal tumor radiation recur metastatically, whereas infants treated with only chemotherapy relapse locally. In murine medulloblastoma model systems, provision of a single dose of radiation to the tumor drives leptomeningeal dissemination. An inflammatory response after radiation-induced tumor cell death recruits a variety of immune cells. Inflammation opens the local blood-brain barrier, allowing intravasation of medulloblastoma cells. Experimental induction of inflammation with lipopolysaccharide drives …

Burden Of Central Nervous System Cancer In The United States, 1990-2021, Hyun Jin Han, Yun Seo Kim, Seoyeon Park, Jae Il Shin, Min Seo Kim, Ju Hyung Moon, Yong Bae Kim, Hazim S Ababneh, Ahmed Abu-Zaid, Demelash Areda, Santhosh Arul, Ahmed Y Azzam, Mainak Bardhan, Mohammad Amin Bayat Tork, Babak Behnam, Gokce Belge Bilgin, Prarthna V Bhardwaj, Soumitra S Bhuyan, Nima Broomand Lomer, Meng Xuan Chen, Suma Sri Chennapragada, Xiaochen Dai, Frances E Dean, Sindhura Deekonda, Xueting Ding, Ojas Prakashbhai Doshi, Abdel Rahman E'Mar, Muhammed Elhadi, Jawad Fares, Patrick Fazeli, James L Fisher, Maryam Fotouhi, Ali Gholamrezanezhad, Fidelia Ida, Chidozie Declan Iwu, Mohamed Jalloh, Chinmay T Jani, Rizwan Kalani, Samuel Berchi Kankam, Foad Kazemi, Ariz Keshwani, Atulya Aman Khosla, Stephen S Lim, Riffat Mehboob, Tomislav Mestrovic, Ali H Mokdad, Christopher J L Murray, Gurudatta Naik, Zuhair S Natto, Dang Nguyen, Fred Nugen, Atakan Orscelik, Romil R Parikh, Louise Penberthy, Richard G Pestell, Disha Prabhu, Jagadeesh Puvvula, Shakthi Kumaran Ramasamy, Cameron John Sabet, Austin E Schumacher, Yigit Can Senol, Sunder Sham, Samendra P Sherchan, Gizeaddis Lamesgin Simegn, Jasvinder A Singh, Ranjan Solanki, Bahadar S Srichawla, Jabeen Taiba, Manoj Tanwar, Mike Tuffour Amirikah, Anjul Verma, Ismaeel Yunusa, David X Zheng, Dong Keon Yon, Keun Young Park

Faculty, Staff and Students Publications

Importance: Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States.

Objective: To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI).

Design, setting, and participants: This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Acute Myeloid Leukemia Drives Atrial Fibrillation Through Tnfα Signaling Activation, Ninad Oak, Jose Alberto Navarro-Garcia, Minhua Li, Mara R Turkieltaub Paredes, Satadru K Lahiri, Bharat K Kantharia, Daisuke Nakada, Xander H T Wehrens, Mohit M Hulsurkar

Faculty, Staff and Students Publications

No abstract provided.

An Annotated Biobank Of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve And Longitudinal Samples During Neoadjuvant Chemotherapy, Amanda L Rinkenbaugh, Yuan Qi, Shirong Cai, Jiansu Shao, Faiza Baameur Hancock, Sabrina L Jeter-Jones, Xiaomei Zhang, Emily Powell, Lei Huo, Rosanna Lau, Chunxiao Fu, Rebekah Gould, Petra Den Hollander, Elizabeth E Ravenberg, Jason B White, Gaiane M Rauch, Banu Arun, Clinton Yam, Alastair M Thompson, Gloria V Echeverria, Stacy L Moulder, W Fraser Symmans, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing …

Early Ctdna Dynamics Inform First-Line Therapy In Patients With Extensive-Stage Small Cell Lung Cancer, Carmela Ciardullo, Luis Tobalina, T Hedley Carr, Philip Szekeres, Silvija Kraljevic, Lauren Averett Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis despite initial treatment responses. This study evaluates ctDNA for monitoring disease and assessing the efficacy of first-line therapy in patients with extensive-stage SCLC (1L ES-SCLC).

Experimental design: In the TAZMAN trial, 31 patients with 1L ES-SCLC received standard treatment with durvalumab and etoposide plus carboplatin or cisplatin. We analyzed 228 plasma samples from 27 of 31 patients using a liquid biopsy approach to detect somatic mutations and copy-number aberrations, while also accounting for clonal hematopoiesis mutations.

Results: Baseline ctDNA analysis detected somatic alterations in 96.3% of …

Preclinical Fluorescence-Guided Imaging Leveraging Surrounding Sentinel Tumor Microenvironment Identifies High-Risk Premalignant Pancreatic Lesions, Shilpa Sharma, Xiaoxia Wen, Jianbo Wang, Beibei Huang, Denise A Hernandez, Cong-Dat Pham, Zhiwen Liu, Susanne Je-Han Lin, Aiko Yamaguchi, Dimitra K Georgiou, Ryan P Coll, H Charles Manning

Faculty, Staff and Student Publications

Purpose: Because surgery is the only potential cure for pancreatic cancer, high-risk premalignant pancreatic lesions often evade detection by palpation or white-light visualization, increasing the risk of recurrence. We asked whether near-infrared fluorescence imaging of tumor-associated inflammation could identify high-risk premalignant lesions, leveraging the tumor microenvironment as a sentinel of local disease and, thus, enhance surgery outcomes.

Experimental design: Fluorescence-guided surgery was performed on genetically engineered mice [Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KSC)] at discrete stages of disease progression, histologically confirmed high-risk, premalignant lesions in postnatal mice to locally advanced pancreatic tumors in adults, using the imaging agent V-1520, a translocator protein …

Genetic Contribution To Treatment-Related Dyslipidemia In Adult Survivors Of Childhood Cancer: Findings From The Ccss, Sjlife, And Dccss-Later Cohorts, Melissa Bolier, Vincent G Pluimakers, Linda Broer, Sebastian J C M M Neggers, Demi T C De Winter, Fan Wang, Jessica L Baedke, André G Uitterlinden, Kateryna Petrykey, Leontien C M Kremer, Jacqueline J Loonen, Marloes Louwerens, Heleen J Van Der Pal, E Lieke A M Feijen, Kevin C Oeffinger, Rebecca M Howell, Eric J Chow, Wendy M Leisenring, Maria Monica M Gramatges, Lindsay M Morton, Leslie L Robison, Melissa M Hudson, Kirsten K Ness, Yadav Sapkota, Gregory T Armstrong, Smita Bhatia, Yutaka Yasui, Marry M Van Den Heuvel-Eibrink

Faculty, Staff and Student Publications

Background: Dyslipidemia can occur as a long-term side effect of childhood cancer treatment. The difference in prevalence among children receiving comparable treatment suggests a role for genetic variation. We conducted the first genome-wide association study on dyslipidemia in a large childhood cancer survivor cohort, using three additional cohorts for replication.

Methods: Discovery analysis was performed in the original Childhood Cancer Survivor Study (CCSS) cohort (N = 4,332). Replication analyses were carried out in the CCSS expansion (N = 2,212), St. Jude Lifetime (N = 2,829), and Dutch Childhood Cancer Survivor Study (DCCSS-LATER) (N = 1,814) cohorts. In the CCSS cohorts, …

Proteomic Perspectives On Kras-Driven Cancers And Emerging Therapeutic Approaches, Ramesh Karki, Ru Chen, Sheng Pan

Faculty, Staff and Student Publications

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS …