Medical Specialties Commons^™

Internet-Delivered Cognitive-Behavioral Intervention For Pain In Pediatric Acute Recurrent And Chronic Pancreatitis: A Multicenter Randomized Controlled Trial, Tonya M Palermo, Rui Li, Chuan Zhou, Homer Aalfs, Gretchen Cress, Mark Lowe, Maisam Abu-El-Haija, Ankur Chugh, Elissa M Downs, Douglas S Fishman, Alvin Jay Freeman, Matthew J Giefer, Tanja Y Gonska, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Robert Adam Noel, Emily R Perito, Fuchenchu Wang, Ying Yuan, Yuhua Zheng, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Abdominal pain is common and associated with high disease burden and health care costs in pediatric acute recurrent (ARP) and chronic pancreatitis (CP). Despite the effectiveness of psychological interventions in other abdominal pain populations, studies have not evaluated these interventions for pediatric pancreatitis pain. We evaluated the feasibility, acceptability, and preliminary efficacy of internet-delivered cognitive-behavioral therapy (CBT) for reducing pancreatitis-related abdominal pain and improving pain interference, anxiety, depression, activity limitations, and health-related quality of life.

Methods: We enrolled 90 adolescents (ages 10-19, 63% female) with ARP or CP and their parents into this randomized placebo-controlled multicenter trial from 15 …

Unusual Endoscopic Remission In An Anti-Tumor Necrosis Factor Refractory Case Of Severe Ulcerative Colitis During Upadacitinib Therapy, Carine A Halaby, Charlotte F Kim, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Author Correction: Nutrient-Sensing Nuclear Receptors Coordinate Autophagy, Jae Man Lee, Martin Wagner, Rui Xiao, Kang Ho Kim, Dan Feng, Mitchell A Lazar, David D Moore

Faculty, Staff and Students Publications

No abstract provided.

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

A Scalable Organoid Model Of Urothelial Aging For Metabolic Interrogation, Infection Modeling, And Reversal Of Age-Associated Changes, Adwaita R Parab, Arnold M Salazar, Steven J Bark, Margarita Divenko, Vasanta Putluri, D'Feau J Lieu, Aadya S Singh, Nagireddy Putluri, Indira U Mysorekar

Faculty, Staff and Students Publications

Aging leads to a progressive decline in overall bladder function resulting in lower urinary tract symptoms and increased susceptibility to infections. However, tissue-specific mechanisms of aging, specifically the contributions of the urothelium, remain elusive. Here, we introduce mouse bladder epithelium-derived organoids (mBEDOs) as a scalable platform to model urothelial aging. mBEDOs from aged mice recapitulate key features of age-associated cellular reprogramming, including oxidative stress, senescence, and DNA damage. We demonstrate the utility of mBEDOs for modeling Uropathogenic Escherichia coli (UPEC) infection, generating assembloids between mBEDOs and macrophages to model epithelial-immune interactions, and genetic perturbation. Using the mBEDO platform, we also …

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Increasing Phytochemical-Rich Foods And Lactobacillus Probiotics In Men With Low-Risk Prostate Cancer – A Randomised, Double-Blind, Placebo-Controlled Trial, Robert J. Thomas, Stacey A. Kenfield, Madeleine Williams, Robert U. Newton, Jeffrey Aldous, Anita Mitra, Zahoor Fazili

Research outputs 2022 to 2026

Men on active surveillance (AS), with prostate cancer, are very interested in dietary strategies that could improve their symptoms and help prevent progression of their disease. In this real-world trial involving 208 men, intake of phytochemical-rich food capsules helped slow prostate-specific antigen (PSA) progression significantly, and improved urinary symptoms and erectile function. What was novel about this study was that men randomised to take an additional blend of five Lactobacillus probiotics had a further three-fold slowing of PSA progression as well as reduction of inflammation. Currently, nearly 50% of men opt out of AS within 5 yr. If confirmed with …

Pathological Response Calculation Assessment Remains Accurate With Reduced Tumor Bed Examination After Neoadjuvant Immunotherapy In Clinically Detectable Stage Iii Melanoma, R. V. Rawson, N. G. Maher, A. M. Menzies, S. N. Lo, N. Mesbah Ardakani, L. A. Jackett, I. A. Vergara, T. E. Pennington, K. F. Shannon, S. Ch’Ng, M. Gonzalez, E. M. Burton, M. W. Lucas, I. L.M. Reijers, E. A. Rozeman, D. E. Gyorki, S. Sandhu, M. S. Carlino, J. Howle, M. Khattak, A. Van Der Westhuizen, M. C. Andrews, V. Atkinson, A. C.J. Van Akkooi, A. J. Spillane, R. P.M. Saw

Research outputs 2022 to 2026

Background: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathological response, determined as percentage residual viable tumor (% RVT), provides critical prognostic information and informs management decisions. Here, we assessed accuracy of %RVT calculation when reduced tumor bed (TB) was examined and leverage these results proposing streamlined protocols for pathological examination. Patients and methods: Comprehensive histopathological examination was carried out on 134 patient specimens after neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by the initial International Neoadjuvant Melanoma Consortium (INMC) protocol was …

Feasibility And Implementation Of Interval-Gap4: A Global Randomised Controlled Trial Of Intense Hybrid-Supervised/Self-Managed Versus Self-Directed Exercise For Metastatic Prostate Cancer, Stacey A. Kenfield, Nicolas H. Hart, Kerry S. Courneya, Rosemary Greenwood, June M. Chan, Jennette Sison, Li Zhang, Sarah Rudman, Leah Ung, Moritz Schumann, Erin L. Van Blarigan, Sam Mckeown, Charles J. Ryan, James Catto, Daniel A. Galvão, Robert U. Newton, Fred Saad

Research outputs 2022 to 2026

Background and objective: Physical activity is associated with a lower risk of mortality in men with prostate cancer (PC); yet, randomised controlled trials with survival endpoints are nonexistent. INTense ExeRcise for surviVAL-Global Action Plan 4 (INTERVAL-GAP4) was a global phase 3 trial designed to test whether structured, hybrid-supervised/self-managed exercise improves survival in men with metastatic PC. The trial was stopped early due to poor accrual. This paper reports feasibility and implementation outcomes. Methods: Men with metastatic PC were randomised (1:1) to a supervised/self-managed moderate- to high-intensity resistance and aerobic programme (three sessions per week for 2 yr) or to self-directed …

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla

Faculty, Staff and Student Publications

MECOM rearrangement in AML involves either inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), where the dislocated GATA2 enhancer drives overexpression of the transcriptional regulator EVI1, causes concomitant GATA2 repression, and promotes AML progression, aggressive phenotype and therapy refractoriness. Treatment with BET protein inhibitor (BETi) induces in vitro and in vivo efficacy in MECOM-r AML cells. Utilizing an unbiased, high-throughput drug screen, focused on mechanistically-annotated drugs, we identified BRD4, PIK3CA, mTOR, BCL-xL and XIAP as dependencies in the MECOM-r AML cells. Monotherapy with mivebresib (BETi), dactolisib (PI3K/mTORi) and LCL161 (IAPi) dose-dependently induced greater lethality in PD MECOM-r versus non-MECOM-r AML cells. RNA-Seq and/or mass spectrometry …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Technical Considerations And Contemporary Literature Review Of The Gore Thoracic Branch Endoprosthesis®, Bruno P Schmid, Lucas R Kanamori, Hannah V Oden-Brunson, Dora Babocs, Ying Huang, Jorge Miranda, Steven Maximus, Gustavo S Oderich

Faculty, Staff and Students Publications

Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for various thoracic aortic pathologies, including blunt thoracic aortic injury, aneurysms, and dissections. Involvement of Ishimaru Zone 2 occurs in up to 60% of TEVAR cases requiring extension across the distal aortic arch and left subclavian artery (LSA). Coverage of the LSA without revascularization increases the risk of complications such as upper extremity ischemia, stroke, and spinal cord injury. Therefore, the preservation of LSA perfusion during TEVAR is essential. Cervical debranching remains an effective alternative to preserve flow to the LSA, but it poses risks of bleeding, infection, and nerve …

Bradycardia, Asystole, And Sudden Cardiac Death In Zc4h2 R198q-Associated Wieacker-Wolff Syndrome, Emily M Masterson, Alexandra M Menillo, Tam Dan Pham, Taylor A Beecroft-Dawson, Steven B Wolfe, Taylor S Howard, Christina Y Miyake

Faculty, Staff and Students Publications

No abstract provided.

Evaluation Of Large Language Models As Decision Support Tools For Head And Neck Cancer Management: A Blinded Multidisciplinary Simulation Study, Sholem Hack, Ron J. Karni, Antonino Maniaci, Christopher E. Fundakowski, Luca Castellani, Fabiola Incandela, Remo Accorona, Miguel Mayo-Yanez, Martina Violati, Lorenzo Giannini, Niccolo' Mevio, Alberto Maria Saibene

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.

METHODS: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.

RESULTS: LLM outputs showed close alignment with expert recommendations. RAG-based …

Investigating The Risk Factors Affecting The Control Of Diabetes And Hypertension In The Refugees Living In Egypt, Noura Seada

Theses and Dissertations

Introduction: Non-Communicable Diseases (NCDs) account for 74% of global deaths, with high prevalence of Diabetes and Hypertension worldwide. Egypt hosts over 1 million registered refugees and asylum seekers, often lacking inclusion in social protection or insurance schemes. This study aimed to assess the factors affecting the control of Type 2 Diabetes (T2D) and Hypertension (HTN) among Syrian and Sudanese refugees in Egypt, focusing on healthcare access, sociodemographic characteristics, lifestyle, and health behaviours.

Methods: This study employed a cross-sectional design using a self-administered questionnaire and BMI measurement. Data were collected from 246 refugees diagnosed with type T2D and/or HTN in the …

Cancer Vaccine Targeting Mutated Gnaq-Expressing Uveal Melanoma, Vitali Alexeev, Mizue Terai, Sergei Koshkin, Olga Igoucheva, Takami Sato

Department of Medical Oncology Faculty Papers

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver …

Global Dose Prescription Variances Exemplified Through Oropharynx Cancer: When Is 70 Gray 70 Gray?, Christian Rønn Hansen, Tony Tadic, Manju Sharma, Gareth Price, Jens Petersen, Mohamed A Naser, Ying Xiao, Nataliya Kovalchuk, Pernille Lassen, Jens Overgaard, Lachlan Mcdowell, Prabhakar Ramachandran, Jun Won Kim, Clifton David Fuller, David J Thomson, Jørgen Johansen, Jeppe Friborg, Sue S Yom, Andrew Hope

Faculty, Staff and Student Publications

Purpose/objectives: Radiation therapy treatment planning hinges on a critical factor: the prescribed dose. Surprisingly, there is no consistent, standardized global approach to evaluating the dosimetry of this prescription across different centers treating head and neck cancer (HNC). This study aimed to quantify global dose variations for identical prescriptions across international centers treating oropharyngeal cancer, to establish the foundation for future outcome-based studies and improve consistency of interpretation worldwide.

Materials and methods: The study included patients with oropharyngeal cancer who were consecutively treated from 2017 onward with intensity-modulated radiation therapy or volumetric modulated arc therapy at 8 globally recognized radiation therapy …

Factors Associated With Upstaging In Patients With Resectable Non-Small Cell Lung Cancer: A Modern Institutional Sample, Sneha Alaparthi, Hamza Rshaidat, Luke Meredith, Scott H. Koeneman, Christina Grindley, Jacob Heilizer, Purab Kothari, Prarthna Chandar, Tyler Grenda, Nathaniel R. Evans Iii, Olugbenga T. Okusanya

Department of Surgery Faculty Papers

BACKGROUND: There is significant value in predicting and better assessing patients who are at risk of post-surgery upstaging in lung cancer. The objective of this study is to review patients who were upstaged following resection and evaluate their clinical and demographic data to elucidate which factors portend an increased risk of pathologic upstaging at our institution (the Thomas Jefferson University Hospital).

METHODS: A retrospective review of institutional data was performed between 2011 and 2023. Patients with stage I-II non-small cell lung cancer (NSCLC) were included. Patients were excluded if they received neoadjuvant systemic therapy, including chemotherapy and/or immunotherapy, and were …

Preoperative Malnutrition Is Associated With Increased Postoperative Complications Following Lumbar Fusion: A Propensity-Matched Analysis, Ali Mehaidli, Muaaz Wajahath, Jad Lawand, Omar Abdalla, Lorenzo Deveza, Noah Hodson, Ryan J Berger, Kevin Taliaferro

Faculty, Staff and Students Publications

Background: Lumbar fusion (LF) is a common surgical intervention for degenerative spinal conditions but carries significant short- and long-term risks. Preoperative malnutrition, characterized by low serum albumin or leukocyte counts, impairs wound healing and increases susceptibility to infection, yet its influence on LF outcomes remains underexplored. This study evaluates the association between preoperative malnutrition and long-term postoperative outcomes following LF.

Methods: Adult patients undergoing LF between 2003 and 2023 were identified in the TriNetX US Collaborative Network. Malnutrition was defined as serum albumin < 3.5 g/dL or leukocyte count < 1,500/mm3 within 1 year preoperatively. A 1:1 propensity score match was performed for demographics, comorbidities, surgical approach, and body mass index (BMI), yielding two cohorts (n=20,693 each). Ninety-day and 5‑year postoperative outcomes were compared using hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Malnourished patients experienced significantly higher 90‑day rates of transfusion (8.4% vs. 4.5%; HR 1.87, 95% CI: …

Unlocking Hope: Mirtazapine's Promise In Obsessive-Compulsive Disorder Treatment, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are first-line treatments for OCD, a significant proportion of patients remain refractory to these interventions. Mirtazapine, an atypical antidepressant with unique pharmacological properties, has emerged as a potential adjunctive therapy for treatment-resistant OCD. This review synthesizes existing evidence regarding the efficacy and safety profile of mirtazapine in OCD management. We analyze clinical trials, observational studies, and case reports, distinguishing high- vs. low-quality evidence, and discuss mechanisms underlying mirtazapine's therapeutic effects. Additionally, …

New Inhibitors Of Neuronal Nitric Oxide Synthase For The Treatment Of Melanoma, Amardeep Awasthi, Anika Patel, Huiying Li, Koon Mook Kang, Christine D. Hardy, Anas Ansari, Raghad Nowar, Hasan Alhaddad, Md. Emtiaz Hasan, Sun Yang, Thomas L. Poulos, Richard B. Silverman

Pharmacy Faculty Articles and Research

In 2024, an estimated 100,640 new cases of invasive melanoma were diagnosed in the U.S., with 9290 deaths. Our previous studies revealed that neuronal nitric oxide synthase (nNOS) derived nitric oxide plays a critical role in melanoma progression, making nNOS inhibition a promising strategy. High structural similarity among NOS isoforms requires careful design of nNOS inhibitors to avoid off-target effects. Our previous lead, HH044, demonstrated potent antimelanoma activity but exhibited only moderate nNOS selectivity. Here, we utilized a structure-based approach to design nNOS inhibitors that promote interactions with human nNOS-specific residue His342. Compound 9 exhibited inhibition of both human ( …

Development Of Dirofilaria Immitis Adult Worms In Nsg Mice, Detection Of Parasite-Derived Microrna And Comparative Analysis Of Laboratory Isolates, Mohini Nakhale, Jessica A. Hess, Ellie Oliver, Nathan M. Ryan, Kirsten Mallon, Omair Sultan, Elinor Willis, Esha Banerjee, Enrico Radaelli, Charles-Antoine Assenmacher, Michael Povelones, Duncan Wells, Russ Morphew, Jennifer Willingham-Lane, Christine Henderson, John Harrington, Paul Mcveigh, David Abraham

Department of Surgery Faculty Papers

Global efforts to control heartworm disease are challenged by increasing drug resistance and inadequate early detection methods, which hinder the effective diagnosis and treatment of Dirofilaria immitis infection. This study presents an in vivo model for investigating D. immitis development and host-parasite interactions. The growth and migration of the D. immitis JYD-34 isolate were analyzed in immunodeficient NSG mice over 177 days, revealing parasite migration to the heart and lungs, which mirrors infection dynamics in the natural canine host. Pathophysiological examination of host tissues revealed early adult-stage worms elicited minimal inflammation. However, with chronicity, mild pulmonary hemosiderin accumulation was observed. …

Factors Influencing Match Success In Integrated Vascular Surgery Residency Programs From 2019 To 2023, Antony A. Fuleihan, Melissa C. Xu, Scott H. Koeneman, Paul J. Dimuzio, Babak Abai, Michael Nooromid

Department of Surgery Faculty Papers

INTRODUCTION: Integrated vascular surgery residency (IVSR) programs have grown increasingly competitive. However, the factors influencing successful matching remain unclear. This study evaluates the impact of medical school and applicant characteristics on IVSR match outcomes.

METHODS: A list of ACGME-accredited IVSRs was obtained from the Society for Vascular Surgery, and resident data from the 2019-2023 match cycles were collected from publicly available sources. Applicant characteristics consisted of additional graduate degrees, Alpha Omega Alpha (AOA) status, and research productivity. Medical school characteristics consisted of ranking, research funding, vascular surgery interest group (VSIG) presence, and vascular surgery faculty size. Logistic regression models were …

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …

Upper Hemisternotomy Vs. Full Sternotomy For Hemiarch And Proximal Aortic Replacement, Jeffrey A. Zucker, Vishal N. Shah, Joshua R. Chen, Christopher Pritting, Colin King, Jacqueline Mcgee, Megary Mccoy, Konstadinos A. Plestis

Department of Surgery Faculty Papers

Introduction: Hemiarch replacement with proximal aortic replacement is seldom performed via upper hemisternotomy (UHS). We report our surgical technique and postoperative outcomes in 11 patients who underwent UHS for hemiarch and proximal aortic replacement, compared with 15 patients who underwent the procedure via full sternotomy (FS).

Methods: A UHS was performed at the right third or fourth intercostal space. Cardiopulmonary bypass (CPB) was established via the distal ascending aorta or right axillary artery and right common femoral vein. After aortic cross-clamping (ACC), the heart was arrested with single-dose antegrade crystalloid cardioplegia. After proximal aortic replacement, hypothermic circulatory arrest (HCA) between …

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …

Two Lysosomal Genes Atp13a2 And Gba1 Interact To Drive Neurodegeneration, Mingxue Gu, Jinghan Zhao, Mingxi Deng, Guang Lin, Xueyang Pan, Wenwen Lin, Mengqi Ma, Jinyong Kim, Seul Kee Byeon, Akhilesh Pandey, Lara M Lange, Chad A Shaw, Jonggeol Kim, Joanne Trinh, Christine Klein, Oguz Kanca, Joshua M Shulman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Background: Parkinson’s disease (PD) is a genetically complex disorder in which combinations of heterozygous risk variants may contribute to pathogenesis. Many PD risk loci encode lysosomal genes, such as GBA1, a common and potent risk factor, conferring at least a 5-fold increase. However, the mechanisms of GBA1 penetrance remain poorly understood.

Methods: Using Drosophila melanogaster, we performed a genetic interaction screen of lysosomal storage disorder (LSD) genes to identify dominant modifiers of Gba1b (fly homolog of GBA1). Age-dependent locomotor assessments, electroretinograms (ERG), transmission electron microscopy (TEM) analyses and quantification of dopaminergic (DA) neurons were used to assess …