Digital Commons Network^™

Acute Kidney Injury Is Associated With Elevated Urinary Endotrophin, Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir M Parikh

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. Although serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI, nor has ETP been evaluated in a pediatric population. Urine samples were collected from a tertiary children's hospital. Medical records were reviewed, and patients who met criteria were sorted into three categories:

In Silico Assessment Of Cellular Damage From Lu-177, Ac-225, And Pb-212 Therapeutic Radionuclides, Konstantinos P Chatzipapas, Konstantinos Papachristou, Dimitris Visvikis, Sebastien Incerti, John D Hazle, George C Kagadis

Faculty, Staff and Student Publications

Background: Targeted radionuclide therapy (TRT) has emerged as a unique and effective treatment modality for cancer. Monte Carlo simulations have greatly advanced investigations into radiation-caused DNA damage, including the complexity of this damage.

Purpose: This study aimed to evaluate DNA damage induced by high-linear energy transfer therapeutic radionuclides used in TRT, specifically 225Ac, 177Lu, and 212Pb, using Geant4-DNA Monte Carlo simulations.

Methods: The Geant4-DNA toolkit, incorporating the "molecularDNA" example, was employed to simulate radiation interactions within a human fibroblast cell model featuring a fractal chromatin fiber geometry within an ellipsoidal nucleus. Three source geometries (membrane, cytoplasm, nucleus) were modeled to …

An Analysis Of How Autistic Burnout Relates To Posttraumatic Stress In Autistic Adults, Antonio F Pagán, Madeline J Bruce, Juliana L Vanderburg, Grace Sattem, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

This study investigated the relationship between autistic burnout and posttraumatic stress symptoms (PTSS) in trauma-exposed autistic adults without intellectual disability (n = 91). Cross-sectional relationships between autistic burnout (measured by the ABSI), PTSS (PCL-5), depression (PHQ-9), and anxiety (GAD-7) were assessed using Pearson correlations. To examine the distinctiveness of autistic burnout from posttraumatic stress, an exploratory factor analysis was conducted on ABSI and PCL-5 data. A strong correlation was found between autistic burnout and PTSS (r = .70, p < .001), an exploratory factor analysis suggested shared underlying factors. These findings indicate a close relationship between autistic burnout and …

Analysis Of Content Related To Retrograde Cricopharyngeal Dysfunction On Tiktok: Opportunities For Patient Education And Advocacy, Aidan Wright, Nathaniel Hunter, Vivian Jin, Andrew Tritter

Faculty, Staff and Student Publications

Objective: TikTok has experienced exponential growth as a social media platform, with over 1 billion active users. Concurrently, retrograde cricopharyngeal dysfunction (RCPD) has seen a surge in awareness among patients and on social media. Our objective was to characterize the most popular RCPD-related content on TikTok.

Methods: The top 50 videos associated with the following hashtags were analyzed: "RCPD," "noburp," "retrograde cricopharyngeal dysfunction," and "noburpsyndrome." Recorded metrics included views, likes, and comments, along with information regarding the creator's identity, gender, geographical location, and the video's purpose.

Results: One hundred and three videos were included in the final analysis, with a …

Delayed Presentation Of A Retained Colonic Segment In A Child With Intestinal Failure On Teduglutide, Rachel C Bordelon, Sarah J Varalla, Varaha S Tammisetti, Mohamed M Shahin, Amanda Tchakarov, Essam Imseis, Allison L Speer

Faculty, Staff and Student Publications

Teduglutide is a glucagon-like peptide 2 (GLP-2) analogue that was approved by the United States Food and Drug Administration for the treatment of pediatric (>1 year) intestinal failure due to short bowel syndrome in 2019. GLP-2 analogues promote rapid intestinal adaptation, increasing the absorptive capacity of residual intestine after surgical resection to aid the achievement of enteral autonomy or reduce parenteral nutrition requirements. Despite relatively few reported side effects, there is a theoretical risk of proliferative complications. Here we present an intriguing case of a pediatric patient found to have a decade-long retained, discontinuous segment of colon from a …

The Mythology Of Polymyositis, Suur Biliciler, Tahseen Mozaffar

Faculty, Staff and Student Publications

Polymyositis (PM) has been in the diagnostic armamentarium in medicine since the mid-nineteenth century. Medicine training puts a heavy emphasis on this diagnosis, and anyone with proximal muscle weakness with elevated serum creatinine kinase is assumed to be PM and a number of patients were rendered this diagnosis without additional testing. This article addresses the historical aspects of the diagnosis of PM and its evolution. We review this literature that addresses the rarity of this diagnosis and rightly puts in perspective in terms of its occurrence in relation to other inflammatory myositides.

Innovations In Thrombectomy Training: A Systematic Review And Expert Recommendations From The Society Of Vascular And Interventional Neurology-Mission Thrombectomy Initiative, Fawaz Al-Mufti, Mohamed Elfil, Abdallah Abbas, Haneen Sabet, Hazem S Ghaith, Ariel Sacknovitz, Ankita Jain, Victor Urrutia, Nabeel Herial, Gabor Toth, Mohamad El-Ghanem, Krishna Amuluru, Viktor C Szeder, Jonathan Crowe, Karol Budohoski, Zurab Nadareishvili, Kaustubh Limaye, Fazeel Siddiqui, Boris Pabon, Ossama Yassin Mansour, Atilla Ozcan Ozdemir, Houman Khosravani, Hamza Shaikh, Nishita Singh, Hesham Masoud, Sushanth R Aroor, Shashvat Desai, Santiago Ortega-Gutierrez, Fredrick Echols, Thanh N Nguyen, Pankajavalli Ramakrishnan, Priyank Khandelwal, Dileep R Yavagal, Kaiz Asif

Faculty, Staff and Student Publications

Background: Mechanical thrombectomy is a critical intervention for patients with acute ischemic stroke with large vessel occlusion. However, significant barriers remain in its widespread implementation, particularly in low- to middle-income countries, including a shortage of trained physicians and limited access to advanced medical technologies. This systematic review and meta-analysis aimed to comprehensively evaluate current mechanical thrombectomy training methodologies and assess their effectiveness in improving procedural skills among neurointerventional teams.

Methods: We conducted a systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, searching PubMed, Scopus, and Web of Science. Eight studies were included, with 3 studies eligible …

Multiomics Reveal Plasma Constituents Associated With Thrombosis Among Trauma Patients Who Do Not Respond To Enoxaparin, Ian S Lacroix, Monika Dzieciatkowska, Francesca Cendali, Kelly Sanders, Charles E Wade, Bryan A Cotton, Mitchell J Cohen, Angelo D'Alessandro, Kirk Hansen, Jessica C Cardenas

Faculty, Staff and Student Publications

Venous thromboembolism (VTE) is among the most common complications affecting patients with severe injuries. Although enoxaparin resistance is common, predicting which patients among this subgroup will develop VTE remains a clinical challenge. The goal of this study was to use multiomics to identify plasma constituents associated with VTE development among trauma patients exhibiting poor responses to enoxaparin. We conducted a secondary analysis of trauma patients at high risk of VTE based on injury characteristics. Plasma was collected daily for the first 8 hospital days. Patients who never responded to enoxaparin were defined as not achieving an anti-factor Xa (FXa) level …

Sweet Syndrome Successfully Treated With Upadacitinib, Valeria Duque-Clavijo, Hung Q Doan, John A Das, Stephen K Tyring

Faculty, Staff and Student Publications

No abstract provided.

Depression Polygenicity And Disease Activity And Disability Worsening In Multiple Sclerosis, Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla Mckay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec

Faculty, Staff and Student Publications

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and …

Characteristics And Outcomes Associated With Multiple Triage Visits Among Patients With Suspected Preterm Labor Or Preterm Premature Rupture Of Membranes, Jameaka L Hamilton, Paula L Mcgee, George R Saade, Rebecca G Clifton, Michael W Varner, Alan T N Tita, Monica Longo, Edward F Bell, Barbara J Stoll, Donna Allard, Ashley Salazar, John M Thorp, Uma M Reddy, Maged M Costantine, Emily S Miller, Dwight J Rouse, Hyagriv N Simhan, Jennifer L Bailit, Lorraine Dugoff, George A Macones, Baha M Sibai

Faculty, Staff and Student Publications

Background: Hospital-based obstetrical triage units frequently serve as an extension to outpatient care. Evaluation of the burden of preterm birth (PTB) typically focuses on the delivery and neonatal periods, while antepartum health care utilization related to risk of PTB is seldom reported.

Objective: To identify the characteristics and outcomes associated with multiple triage visits among patients with suspected preterm labor (PTL) or preterm premature rupture of membranes (pPROM).

Study design: Secondary analysis of a retrospective cohort study of all triage visits from 20 0/7 through 34 6/7 weeks gestation on randomly selected dates in 2019 at 34 hospitals across the …

Transforming Preterm Care: The Power Of Small Baby Guidelines In Enhancing Outcomes, Leeann Pavlek, Debra Armbruster, Cecilie Halling, Kaitlyn Hipp, Maria Jebbia, Susan Lopata, Matthew Rysavy, Rebecca Saliga, Sheria Wilson, Claire Beaullieu

Faculty, Staff and Student Publications

As survival rates of extremely preterm (EPT) infants continue to improve, focus has shifted to reduce morbidity and complications in these vulnerable patients. Management of EPT infants presents significant clinical, logistical, and sometimes ethical challenges. Outcomes across centers are highly variable and strongly influenced by the care provided in the early neonatal period. Standardized guidelines, based on published literature and center-specific experiences, play an important role in improving outcomes for EPT infants. Multidisciplinary guidelines provide a framework for clinical management and support a consistent care approach. Guidelines can improve care throughout the entire neonatal intensive care unit (NICU) course, beginning …

The Distal Acromial Tip Fusion: A Novel Procedure To Mitigate Acromial Stress Fractures In High-Risk Patients Undergoing Reverse Shoulder Arthroplasty, Trevor G Simcox, Jeffrey Dela Cruz, Gennaro Dellicarpini, Wojciech K Dzieza, Itaru Kawashima, Kevin W Farmer, Jonathan O Wright, Thomas W Wright, Joseph J King

Faculty, Staff and Student Publications

Acromion and scapular spine fractures (ASFs) pose significant challenges in the management of patients undergoing reverse total shoulder arthroplasty and there is a pressing need for effective preventive measures. Current predictive factors for ASF include female sex, osteoporosis, older age, and anatomical considerations such as glenoid medialization and acromial morphology. However, surgical options to mitigate ASF risk are limited. In this study, we propose a novel technique: incorporation of distal acromial tip fusion (DATF) during primary reverse total shoulder arthroplasty procedures. DATF involves bony fusion between the undersurface of the anterolateral acromion and the region where the superior rim of …

Prevalence Of Obesity With Confirmed Excess Adiposity In Us Children And Adolescents, Alexandra B Palmer, Kyung Hyun Lee, Rashedeh Roshani, Elizabeth Frankel, Miryoung Lee, Mohammad Y Anwar, Heather M Highland, Kristin L Young, Mariaelisa Graff, Joseph B Mccormick, Susan P Fisher-Hoch, Joyce P Samuel, Jennifer E Below, Kari E North, Penny Gordon-Larsen

Faculty, Staff and Student Publications

No abstract provided.

Functional Ability Profiles In Beta-Propeller Protein-Associated Neurodegeneration (Bpan), Francesco Gavazzi, Samuel R Pierce, Vanessa Smith, Eric Yang, Julie Skorup, Kristy Pucci, Emma Kotes, Allan M Glanzman, Stacy V Cusack, Todd Levy, Holly Dubbs, Emma Wiener, Sarah Woidill, Joseph Vithayathil, Abbas Jawad, Nivedita Thakur, Laura A Adang

Faculty, Staff and Student Publications

Background: Beta-propeller Protein-Associated Neurodegeneration (BPAN) is a rare neurodevelopmental degenerative disorder caused by pathogenic variants in WDR45 leading to brain iron accumulation. Its rarity and complex clinical course make it difficult to select appropriate clinical outcome assessments (COAs). This study evaluates established COAs for feasibility and effectiveness in capturing BPAN's functional ability profiles exploring cognitive, motor, and behavioral features.

Methods: We performed an observational study. Children were recruited as part of the Myelin Disorders Biorepository Project at the Children's Hospital of Philadelphia. We administered the Gross Motor Function Measure-88 (GMFM-88), the Leiter International Performance Scale (Leiter-3), and the Vineland Adaptive …

Priming With Transcutaneous Spinal Direct Current Stimulation Followed By Robotic Exoskeleton Gait Training In Individuals With Spinal Cord Injury: A Case Series, Marcie Kern, Catherine Velasquez-Ignacio, Taimoor Afzal, Shih-Chiao Tseng, Gerard E Francisco, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

Objectives: To investigate the safety and feasibility of repeated transcutaneous spinal direct current stimulation (tsDCS) as priming strategy during exoskeleton-assisted locomotor training in individuals with SCI and evaluate potential neurophysiologic and functional gait changes.

Study design: Case series experimental design.

Setting: Research laboratory at a post-acute rehabilitation hospital.

Participants: Four participants with chronic incomplete SCI.

Interventions: Four participants with chronic incomplete SCI received three weeks of training consisting of two types of interventions after baseline (A): 20-minute tsDCS (anode or cathode) applied over the spinous processes of T10 followed by 20-minute exoskeleton-assisted locomotor training (B, B1, B2) and 20-minute exoskeleton-assisted …

From Reflex Reaction To Rational Action-Personalizing Surgical Antibiotic Prophylaxis, Renee W Green, William D Rieger, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Perceived Prejudice Or Discrimination In Medical Care Among Us Adults, Inimfon Jackson, Robert Yu, Joël Fokom Domgue, Sanjay Shete

Faculty, Staff and Student Publications

No abstract provided.

Misfolded Amyloid-Beta Conformational Variants (Strains) As Drivers Of Alzheimer's Disease Neuropathology, Salvatore Saieva, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Phase 2 Study Of Monotherapy With Pembrolizumab For Advanced Adrenocortical Carcinoma, Brenda Chahla, Bettzy Stephen, Juhee Song, Vania Balderrama-Brondani, Feyza Yaylaci, Matthew T Campbell, Aung Naing, Mouhammed Amir Habra

Faculty, Staff and Student Publications

Introduction: Adrenocortical carcinoma (ACC) is a rare cancer with suboptimal response to chemotherapy. The role of immunotherapy in ACC management is evolving.

Methods: An investigator-initiated, open-label, phase 2 clinical trial was performed to ascertain the activity and safety of monotherapy with pembrolizumab (a humanized monoclonal anti-programmed cell death protein 1 antibody) in patients with advanced ACC. This study was part of a basket clinical trial (ClinicalTrials.gov ID: NCT02721732). Study participants were enrolled from August 15, 2016, until December 7, 2020. Pembrolizumab (200 mg) was administered intravenously every 3 weeks. All other lines of therapy, including mitotane, were stopped before …

Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed By Adjuvant Durvalumab In Resectable Nsclc, Tetsuya Mitsudomi, John V Heymach, Martin Reck, Janis M Taube, Shugeng Gao, Yoshitsugu Horio, Jian You, Gaofeng Li, Dinh Van Luong, Somcharoen Saeteng, Fumihiro Tanaka, Stefan B Watzka, Laszlo Urban, Zsuzsanna Szalai, Hiroaki Akamatsu, Jin Hyoung Kang, Francisco J Orlandi, Guzel Z Mukhametshina, Andreas Pircher, Carlos Henrique Andrade Teixeira, Mike Aperghis, Gary J Doherty, Ruth Doake, Tamer M Fouad, David Harpole

Faculty, Staff and Student Publications

Introduction: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN.

Methods: Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics.

Results: A total of 737 out of 740 mITT patients received treatment, 366 and 371 in the durvalumab and …

Sars-Cov-2 Mrna Vaccines Sensitize Tumours To Immune Checkpoint Blockade, Adam J Grippin, Christiano Marconi, Sage Copling, Nan Li, Chen Braun, Cole Woody, Elliana Young, Priti Gupta, Min Wang, Annette Wu, Seong Dong Jeong, Dhruvkumar Soni, Frances Weidert, Chao Xie, Eden Goldenberg, Andrew Kim, Chong Zhao, Anna Devries, Paul Castillo, Rishabh Lohray, Michael K Rooney, Benjamin R Schrank, Yifan Wang, Yifan Ma, Enoch Chang, Ramez Kouzy, Kyle Dyson, Jordan Jafarnia, Nina Nariman, Gregory Gladish, Jacob New, Ada Argueta, Diana Amaya, Nagheme Thomas, Andria Doty, Joe Chen, Nikhil Copling, Gabriel Alatrash, Julie Simon, Alicia Bea Davies, William Dennis, Richard Liang, Jeff Lewis, Xiong Wei, Waree Rinsurongkawong, Ara A Vaporciyan, Andrew Johns, D3code Team, Jack Lee, Ji-Hyun Lee, Ryan Sun, Padmanee Sharma, Hai Tran, Jianjun Zhang, Don L Gibbons, Jennifer Wargo, Betty Y S Kim, John V Heymach, Hector R Mendez-Gomez, Wen Jiang, Elias J Sayour, Steven H Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1–9. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes10–14. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for …

Cardiovascular Multimorbidity In Older Adults In The United States By Race And Sex, Michael D Green, Robert J Mentz, Stephen J Greene, Bradley G Hammill, Utibe R Essien, Ying Xian, Erin D Michos, Roland J Thorpe, Matthew E Dupre, Brian Mac Grory, Chi-Tsun Chiu, Emily C O'Brien, Jay B Lusk

Faculty, Staff and Student Publications

Background: It is essential to understand the prevalence of cardiovascular multimorbidity and to recognize disparities by race and sex to promote health equity.

Objectives: The objectives of the study are to investigate disparities in the development and progression of cardiovascular multimorbidity among older adults in the United States and estimate relative life expectancies among patients with cardiovascular multimorbidity.

Methods: This was a nationwide study of a 5% nationwide sample of fee-for-service Medicare beneficiaries aged 65 or older from 2010 to 2020. Multistate survival models were employed to estimate cardiovascular disease (CVD) progression and a microsimulation approach was used to derive …

Acute And Chronic Nasal Inflammation Induces Lymphangiogenesis In The Olfactory Mucosa In Mice, Suzuho Komaki, Ryuichi Imai, Yuzuki Sugimoto, Rei Settsu, Aki Obara, Atsuyoshi Shimada, Robert Dantzer, Geoffroy Laumet, Fumiaki Imamura, Sanae Hasegawa-Ishii

Faculty, Staff and Student Publications

Background: Lymphangiogenesis, the formation of new lymphatic vessels, is primarily driven by VEGF-C-mediated activation of VEGFR-3 and plays a critical role in immune regulation and tissue repair. Although lymphangiogenesis has been well documented in various inflamed tissues, its occurrence and spatiotemporal characteristics in the olfactory mucosa during nasal inflammation remain poorly understood. To address this, we investigated the localization and development of lymphatic vessels in a mouse model of both acute and chronic nasal inflammation.

Methods: Acute inflammation was induced by intranasal administration of lipopolysaccharide (LPS; 10 μg per nostril) in 8-week-old male mice, with saline-treated mice as controls. Behavioral …

Omacetaxine And Venetoclax In Relapsed/Refractory Acute Myeloid Leukemia Or Myelodysplastic Syndrome With Mutant Runx1, Courtney D Dinardo, Wei-Ying Jen, Guillermo Montalban-Bravo, Xuemei Wang, Sanam Loghavi, Sravanthi Lavu, Nicholas J Short, Kelly Chien, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Michael Andreeff, Gautam Borthakur, Tapan M Kadia, Naval G Daver, Guillermo Garcia-Manero, Christopher P Mill, Xiaoping Su, Warren Fiskus, Kapil N Bhalla

Faculty, Staff and Student Publications

Mutations in RUNX1 (RUNX1mut) occur in 10% to 20% of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and are associated with poor outcomes to standard therapy. Omacetaxine mepesuccinate (OM), a semisynthetic analog of homoharringtonine, has been shown to be lethal to RUNX1mut AML cells in vitro through reduction of MCL1 and BCL-XL, and synergizes with venetoclax (VEN) in RUNX1mut AML models. We investigated the safety and efficacy of OM + VEN in relapsed/refractory RUNX1mut MDS/AML in a Bayesian Optimal Interval design. VEN 400 mg daily from days 1 to 14 and OM …

Missing The Target: A Scoping Review Of The Use Of Percent Weight Loss For Obesity Management, Diana Sherifali, Megan Racey, Donna Fitzpatrick-Lewis, Michelle Greenway, Sanjeev Sockalingam, Jun Wada, Soo Huat Teoh, Ian Patton, David Macklin, Elizabeth F C Van Rossum, Luca Busetto, Deborah Bade Horn, J D Patricia Nece, Morgan Emile Gabriel Salmon Leguede, Nicole Pearce, Carel Le Roux, Jamy Ard, Angela S Alberga, Lee Kaplan, Arya M Sharma, Sean Wharton

Faculty, Staff and Student Publications

Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.

Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted …

Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis In Ectopic Cushing Syndrome, Raghavendra Pandit, Chethan Yamichannaiah, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Tushar Bandgar

Faculty, Staff and Student Publications

A woman in her fourth decade of life with metastatic ectopic Cushing syndrome due to a thymic neuroendocrine tumor developed an acute adrenocorticotropin (ACTH)-mediated hypercortisolemic crisis 5 days after initiating lutetium-177-labeled DOTA-[Tyr3]-octreotate (177Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). She presented with hypertension, rapid weight gain (8 kg in a week), psychosis, and biochemical evidence of severe hypercortisolism: serum cortisol: 141 µg/dL (SI: 3889.7 nmol/L) (reference range, 5-25 µg/dL [SI: 137.9-689.7 nmol/L]), plasma ACTH greater than 2000 pg/mL (SI >440.4 pmol/L) (reference range, 10-60 pg/mL [SI: 2.2-13.3 pmol/L]), potassium: 3.4 mEq/L (reference range, 3.5-5.0 mEq/L). Low-dose intravenous etomidate (0.02 mg/kg/h) was …

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

Apol2 Stabilizes Ku80 To Confer Nhej-Mediated Radioresistance In Gastric Cancer, Dan Zu, Qimei Bao, Hanyi He, Yuke Zhong, Mingcong Deng, Yangchan Hu, Chunkai Zhang, Chen Liang, Yixing Huang, Haidong Liu, Xiao Li, Yanhua He, Guoyan Luo, Weixin Wu, Fenghui Guan, Shengfeng Xu, Min Liu, Albino Bacolla, Ji Jing, Yian Du, John A Tainer, Yin Shi, Zu Ye, Xiangdong Cheng

Faculty, Staff and Student Publications

Radiotherapy is one of the most important adjuvant treatment methods for gastric cancer (GC). However, radioresistance remains a major clinical obstacle. In this study, APOL2 is identified as a key player in promoting non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair and enhancing radioresistance in GC. Bioinformatics and clinical data revealed that high APOL2 expression is correlated with poor prognosis in GC patients. Functional experiments showed that APOL2 overexpression enhances genomic stability by accelerating DSB repair via the NHEJ pathway, while APOL2 knockout impairs repair capacity. Mechanistically, APOL2 binds to and stabilizes Ku80 by enhancing USP7-mediated deubiquitylation, thereby increasing Ku80 …

Genome Sequencing Reveals The Impact Of Pseudoexons In Rare Genetic Disease, Georgia Pitsava, Megan Hawley, Light Auriga, Ivan De Dios, Arthur Ko, Sofia Marmolejos, Miguel Almalvez, Ingrid Chen, Kaylee Scozzaro, Jianhua Zhao, Rebekah Barrick, Nicholas Ah Mew, Vincent A Fusaro, Jonathan Lotempio, Matthew Taylor, Luisa Mestroni, Sharon Graw, Dianna Milewicz, Dongchuan Guo, David R Murdock, Kinga M Bujakowska, Changrui Xiao, Emmanuèle C Délot, Seth I Berger, Eric Vilain

Faculty, Staff and Student Publications

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.

Results: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) …