Medicine and Health Sciences Commons^™

Weight Loss And A Shunt On “Off”: An Odd Case Of Overshunting In An Idiopathic Intracranial Hypertension Patient Illustrative Case, Thomas Hamre, Ashley Ricciardelli, Alex Flores, Ashwin Viswanathan

Faculty, Staff and Students Publications

Background: CSF diversion with ventriculoperitoneal (VP) shunts is a common treatment for idiopathic intracranial hypertension (IIH). Rarely, overshunting can occur. Diagnosing and managing overshunting in an IIH patient with a shunt can be challenging. The authors present a unique etiology of overshunting successfully treated with shunt ligation.

Observations: A 48-year-old female with IIH who had undergone VP shunt placement with a programmable Certas valve presented with symptoms concerning for low-pressure headaches following a 25-kg weight loss. Intracranial pressure (ICP) monitoring along with an inpatient headache diary facilitated the diagnosis of intracranial hypotension secondary to CSF overdrainage through the shunt. Following …

Dissemination Of A Facilitation Strategy To De-Implement Unnecessary Post-Operative Antibiotics At Children's Hospitals: The Optimizing Perioperative Antibiotic In Children (Operatic) Trial 2.0, Emmanuel K Tetteh, Harry Obeng, Andrew Atkinson, Sara Malone, Matt Sattler, Tyler Walsh, Lauren Walsh, Jacqueline M Saito, Shawn J Rangel, Jason G Newland, Virginia R Mckay

2020-Current year OA Pubs

BACKGROUND: Excessive postoperative antibiotic use in pediatric surgical patients contributes to antibiotic resistance and increases the risk of Clostridioides difficile infection. Despite established guidelines recommending limited postoperative antibiotic duration, many hospitals struggle with de-implementation. This study aims to disseminate and evaluate the impact of a combined strategy to reduce unnecessary postoperative antibiotic use which combines enhanced antimicrobial stewardship program facilitation, defined as a set of actions to enable implementation, combined with order set review and modification. This multi-center study builds on an initial stepped wedge cluster randomized trial involving nine children's hospitals, where facilitation training improved implementation of surgical prophylaxis …

Use And Reporting Of Intervention Mapping For Adaptation: A Systematic Review Protocol, Eunyoung Kang, Hugo R Sánchez-Blas, Elizabeth O Obekpa, Maria E Fernandez

Faculty, Staff and Student Publications

Introduction: Intervention adaptation is likely to occur to some extent when implementing interventions in new implementation contexts. Using systematic frameworks can guide intentional and effective adaptation processes. Intervention Mapping for Adaptation (IM-ADAPT) is a framework that offers step-by-step guidance for systematic, theory-based intervention adaptation. Despite the increasing use of IM-ADAPT, there is limited understanding of the contexts in which it has been applied and how effectively it is used and reported. Addressing this knowledge gap can improve current adaptation practices and inform future enhancements of the IM-ADAPT framework and the broader science of intervention adaptation. This review aims to (1) …

Social Determinants Of Health Patterns In Children With Severe Disease Due To Sars-Cov-2 Infection-An Exploratory Approach, Joshua Prabhu, Sebastian Acosta, Fabio Savorgnan, Ananth V Annapragada, Usha Sethuraman

Faculty, Staff and Students Publications

Background/Objectives: Research on the association of adverse social determinants of health (SDOH) with severe pediatric coronavirus disease (COVID-19) is limited. We examined associations between SDOH patterns and COVID-19 severity in children.

Methods: We conducted a prospective, observational study of children (< 18 years) with symptomatic SARS-CoV-2 infection evaluated in an urban pediatric emergency department (March 2021-April 2022) in Detroit, Michigan. Caregivers completed a 34-item survey based on the Healthy People 2030 framework. Severe disease was defined as the occurrence of respiratory/cardiac failure or death within four weeks of diagnosis. Continuous and categorical variables were described using medians and percentages, respectively. Associations between disease severity and risk factors were determined using chi-square tests. Association rule mining was used for feature selection, followed by multivariate logistic regression.

Results: We analyzed data from 354 children [6-12 years: 31.1%, Female: 51.1%, Black: 59%, not Hispanic: 84.7%, public insurance: 77.1%, chronic condition: 27.4%]. Of the total, 113 children had severe disease. Most caregivers were 30-44 years old (53.1%), had less than a college degree (70.4%), and income < USD 50,000 (75.2%). Adverse SDOH reported included food/housing insecurity (24.6%), no support (64.7%), unmet childcare needs (35.9%), and lack of transportation (12.7%). After controlling for age, sex, medical history, income, and obesity, severe disease was associated with caregiver use of drugs/alcohol (OR:5.92, p < 0.001) and social discrimination/lack of support (OR: 1.74, p = 0.030).

Conclusions: Two SDOH patterns (caregiver use of drugs/alcohol …

Surgical Success Following Robotic Upper Urinary Tract Reconstruction, Results From A Global Network Of Healthcare Organizations, Zachary Prebay, Adam Schneider, Sohan S. Shah, Mauro Dispagna, Mihir S. Shah

Department of Urology Faculty Papers

INTRODUCTION: Available data on robotic ureteral reconstruction procedures is concentrated from high volume centers. To better understand generalizability of success, we used a network of healthcare organizations (HCOs) to evaluate surgical success following robotic-assisted pyeloplasty (RP), ureteral reimplantation (RR), and ureteroureterostomy/ureteroplasty (RU).

METHODS: We searched the TriNetX database for adult (>18 years old) patients undergoing RP, RR and RU. Our primary outcome was need for drain placement (nephrostomy or ureteral stent) from 4 weeks to 10 years postoperatively. We evaluated risk factors (RF) for drain placement (vascular disease, kidney disease, diabetes (DM), smoking history, radiation history, age, body mass …

Risk Analysis Index As A Predictor Of Mortality And Failure To Rescue In Patients Undergoing Distal Femur Fracture Fixation., Kush Modi, Omar Sbaih, Jared Sasaki, Victor Koltenyuk, Nithin Gupta, Hursch Patel, James D Miller

Medical Education Articles

PURPOSE: This study sought to evaluate the use of frailty, compared to age alone and American Society of Anesthesiologists (ASA) score, for prediction of mortality and failure to rescue (FTR) in patients undergoing surgical fixation of distal femur fractures (DFFs).

METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for patients who underwent surgical management of DFFs. Frailty was evaluated using the 5-Item Modified Frailty Index (mFI-5) and Risk Analysis Index (RAI). Outcomes included 30-day mortality and FTR (mortality following major complication). Multivariate regression and receiver operating characteristic curve (AUROC) analyses were performed to …

Rbm39 Contributes To Mgmt Maintenance In Response To Temozolomide-Induced Dna Damage, Vahid Khalaj, Jack T Adams, Solmaz Aghaamiri, Servando Hernandez Vargas, Tyler M Bateman, Sukhen C Ghosh, Majid Momeny, Ali Azhdarinia

The Brown Foundation: Institute of Molecular Medicine

Resistance to alkylating chemotherapeutic agents such as temozolomide (TMZ) is a significant challenge in treating tumors with high MGMT expression, including MGMT-positive glioblastoma and neuroendocrine neoplasms. In this study, we investigated the effect of RNA-binding motif protein 39 (RBM39) downregulation on MGMT protein levels, based on prior observations suggesting an association between these two proteins. Pharmacological depletion or siRNA-mediated knockdown of RBM39 led to a marked reduction in MGMT protein levels in MGMT-expressing cancer cells. We further showed that dual targeting of RBM39 (using indisulam) and MGMT (with O6-benzylguanine) synergistically enhanced MGMT depletion. Functionally, combined indisulam and TMZ treatment significantly …

Untargeted Metabolomics Reveals Organ-Specific And Extraction-Dependent Metabolite Profiles In Endemic Tajik Species Ferula Violacea Korovin, Sylhiya Mavlonazarova, Kenneth Acosta, Rinat Abzalimov, Saidbeg Satorov, Vyacheslav Dushenkov

Publications and Research

Ferula violacea Korovin, an endemic Tajikistani plant with purported medicinal properties, remains understudied. This study employs untargeted metabolomics to characterize the metabolite profiles of ethanol extracts and juices from F. violacea roots and seeds. In total, 540 distinct metabolites are putatively identified, 419 of which are previously unreported in the Ferula genus, representing a substantial expansion of its known chemical diversity. The most abundant metabolites are terpenoids, amino acid derivatives, and alkaloids. A particularly abundant group of daucane sesquiterpenoids, sharing a common (6-methyl-azulen-4-yl) cyclohexanecarboxylate substructure, is identified, including known metabolites such as ferutidin and ferutinin. Comparative analysis reveals organ-specific metabolic …

Hyperoxia During Neonatal Cardiopulmonary Bypass Is Associated With Worse Clinical Outcomes: A Multi-Institutional Study, Asaad G Beshish, David M Kwiatkowski, Nathaniel Sznycer-Taub, John M Costello, Andrew Jergel, Scott Gillespie, Katherine Cashen, Ahmed Asfari, Maria Batsis, Jason R Buckley, Meghan M Chlebowski, Saul Flores, Nimrod Goldshtrom, Karl Migally, Kimberly I Mills, Monique R Radman, Chetana Reddy, Brittany Shutes, Christine M Riley, Sukumar Suguna Narasimhulu, Dana Mueller, Venugopal Amula, Raji Venkitachalam, Brian F Joy, Karan B Karki, Scott M Leopold, Jennifer E Schramm, Christine A Capone, Scott I Aydin, Adnan M Bakar, Kieran Leong, Agnieszka Kulikowska, Sarah Wing, Christopher W Mastropietro, Collaborative Research From The Pediatric Intensive Care Society (Core‐Pcics) Investigators

Faculty, Staff and Students Publications

Background: Exposure to supraphysiologic oxygen concentrations, or hyperoxia, during neonatal cardiopulmonary bypass (CPB) has been associated with worse outcomes in single-center studies. We aimed to describe variation in oxygen exposure during CPB and determine if hyperoxia is associated with worse outcomes in a multicenter cohort of neonates undergoing cardiac surgery.

Methods: We conducted a retrospective study of neonates who underwent surgery with CPB between January 2021 and December 2022 at 29 centers. Primary outcomes were operative mortality and major adverse cardiovascular events (MACE), which included CPR, extracorporeal support, stroke, and mortality. Logistic regression assessed the associations between median PaO2 during …

Glucagon-Like Peptide 1 Receptor Agonists And The Clinical Outcomes Of Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Ahmed B Bayoumy, Lindsay M Clarke, Parakkal Deepak, Aakash Desai, Priya Sehgal, Uri Gorelik, Haggai Bar-Yoseph, Marie Villumsen, Chris J J Mulder, Dirk J Stenvers, Maarten E Tushuizen, Nanne K H De Boer

2020-Current year OA Pubs

BACKGROUND: Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery, and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD.

METHODS: A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to March 15, 2025. Studies reporting outcomes …

Artificial Intelligence (Ai) In Pharmaceutical Formulation And Dosage Calculations., Sameer Joshi, Sandeep Sheth

PCOM Scholarly Works

Artificial intelligence (AI) is reforming pharmaceutical sciences by renovating traditional drug formulation and dosage calculation approaches. This review provides a comprehensive overview of how AI technologies, such as machine learning (ML), deep learning (DL), and natural language processing (NLP), are currently being used in pharmaceutical calculations to improve accuracy, efficiency, and personalization. We have explored the role of AI in predicting drug properties, excipient optimization, and formulation design, as well as its applications in pharmacokinetic/pharmacodynamic (PK/PD) modeling, real-time dose adjustment, and precision medicine. Despite significant progress, data quality, interpretability, regulatory acceptance, and ethical considerations persist. Therefore, this review examines the …

Brief Report: Lung Cancer Diagnoses Among Lung Cancer Screening Program Participants With Family History Of Lung Cancer, Julia G. Katcher, Christine S. Shusted, Padmanabh Bhatt, Brooke M. Ruane, Jenna Markle, Gregory C. Kane, Kuang-Yi Wen, Hee-Soon Juon, Julie A. Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Clinical Practice Points

• Among screening-eligible adults, lung cancer is diagnosed more often in those with family history of lung cancer
• Patients with family history had higher frequency of stage IV disease
• Considering family history in risk assessment could improve lung cancer screening strategies

Perceived Risks, Reasons For Use, And Barriers To Cessation Among Youth Who Use Multiple Tobacco Products, Sierra L. Patterson, Isabellle Duguid, Sonia A. Clark, Seth M. Noar, Allison J. Lazard, Jim F. Thrasher Ph.D., Ma, Ms, Adam O. Goldstein, Sarah D. Kowitt

Faculty Publications

Background

Many interventions aim to reduce youth tobacco use, but few have focused on youth who use multiple tobacco products (MTPs). This qualitative study sought to understand how youth who use MTPs view tobacco product risks, describe reasons for MTP use, and perceive barriers and facilitators to cessation.

Methods

We conducted seven virtual focus groups with 30 US youth ages 14–20 years who reported using e-cigarettes and smoking a combustible tobacco product in the past 30 days. We used a semi-structured focus group guide to ask youth about perceived health risks of tobacco products, reasons for MTP use, and thoughts …

Finding Solutions: Meeting Essential Needs To Overcome Health And Educational Inequities Among College Students, Nicholas Freudenberg, Rashida Crutchfield

Publications and Research

Many economic, academic, and social factors influence college completion, and scholars have documented that a significant cause of students leaving school before graduation is that many do not have their basic needs for food, housing, and health care met. These barriers undermine their academic success by forcing students to reduce the time spent on their studies, work more hours, or stop out of school to support themselves or their families. Unmet essential needs jeopardize academic and life success for students in higher education across the United States and widen racial/ethnic and class inequities in college completion and health. Our review …

Standardizing And Scaffolding Health Care Ai-Chatbot Evaluation: Systematic Review., Yining Hua, Winna Xia, David Bates, George Hartstein, Hyungjin Tom Kim, Michael Li, Benjamin Nelson, Charles Stromeyer Iv, Darlene King, Jina Suh, Li Zhou, John Torous

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Health care chatbots are rapidly proliferating, while generative artificial intelligence (AI) outpaces existing evaluation standards.

OBJECTIVE: We aimed to develop a structured, stakeholder-informed framework to standardize evaluation of health care chatbots.

METHODS: PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)-guided searches across multiple databases identified 266 records; 152 were screened, 21 full texts were assessed, and 11 frameworks were included. We extracted 356 questions (refined to 271 by deduplication and relevance review), mapped items to Coalition for Health AI constructs, and organized them with iterative input from clinicians, patients, developers, epidemiologists, and policymakers.

RESULTS: We developed the Health …

Personalized Resistance Exercise With Peer Support For Women With Pcos Using A Smart Home Video Device: Pilot Randomized Controlled Trial Guided By Self-Determination Theory, Pamela J. Wright Phd, Ms, Med, Rn, Cen, Cynthia F. Corbett Phd, Rn, Faan, Kesheng Wang

Faculty Publications

Background

Women with polycystic ovary syndrome (PCOS) report exercise barriers as stigma-related stress, lack of peer support, and facility issues. “Resistance exercise (RE) with peer support and bands/ball and digitally-based supervision” (REPS w/BANDS) was designed to help mitigate exercise barriers. Underscored by self-determination theory (SDT), the 12-week intervention was remotely delivered via digital technology and inclusive of peer support.

Purpose

The purposes of this pilot randomized controlled trial (RCT) were to test the feasibility and acceptability of REPS w/BANDS and explore signals of within- and between-group differences on outcomes (e.g., depressive symptoms and fitness).

Methods

Participants (N = 25) …

Pathways And Challenges In The Clinical Translational Of Radiopharmaceuticals For Pediatric Investigations, Erik Stauff, Hanieh Karimi, Heidi H. Kecskemethy, Thomas H. Shaffer, Reza Vali, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical development and clinical translation face numerous scientific, ethical, and regulatory challenges, particularly within the pediatric population. Although molecular imaging holds significant promise for improving diagnosis and treatment across a spectrum of diseases, including pediatric-specific conditions like Kawasaki disease, autism spectrum disorders, attention-deficit/hyperactivity disorder, and neuroblastoma, the path from discovery to clinical application remains problematic. The U.S. Food and Drug Administration (FDA) provides three primary pathways-traditional Investigational New Drug (IND) applications, exploratory Investigational New Drug application (eIND), and the Radioactive Drug Research Committee (RDRC) mechanism-to facilitate clinical translation of radiotracers. However, these frameworks are not specifically tailored to pediatric needs. …

Beyond Distraction: Music Therapy For Chronic Pain Management In People With Advanced Cancer, Joke Bradt, Lynn Gumert, Carrie Cottone, Ming Yuan Low, Clarissa Lacson, Kate Myers-Coffman, Karolina Bryl, Preethi Selvan, Jacelyn Biondo, Allison Millstein, Anna Cephas, Stephenie Sofield, Brooke Worster, Amy Leader

Department of Medical Oncology Faculty Papers

OBJECTIVE: Effective, non-pharmacological approaches to pain management for people with advanced cancer that can enhance quality of life while minimizing adverse effects are urgently needed. While music therapy has been demonstrated to be effective in reducing pain and improving pain-related outcomes across various patient populations, it has not been specifically examined in addressing chronic pain among people with advanced cancer. This study aims to enhance understanding of how people with advanced cancer experience music therapy for pain management.

METHODS: As part of a mixed methods intervention trial, we conducted semi-structured interviews with a subsample of 25 outpatients with advanced cancer …

Nanodiamonds In Advancing Biomedical Sciences, Ebenezer Owusu, Sofia Lerma, Jinhyeong Jang, Deepa Roy, Shizue Mito, Upal Roy, Elena A. Rozhkova

Health & Biomedical Sciences Faculty Publications

Nanodiamonds (NDs), tetrahedral carbon structures with a size ranging from 1 to 100 nm, have gained growing attention in recent years due to their distinct optical, thermal, and mechanical properties compared to other carbon nanomaterials (e.g., graphene, carbon nanotubes, carbon dots). Combined with a high surface-to-volume ratio and tunable and chemically versatile surfaces, these support broad applications across catalysis, electronics, and life sciences. Moreover, the biocompatible characteristics of NDs enable their controllable interfacial interactions with biological systems, positioning them as excellent candidates for advancing cutting-edge biomedical sciences, particularly through the engineering of efficient material biointerfaces that facilitate optimal interactions with …

A High-Density Diffuse Optical Tomography Dataset Of Naturalistic Viewing, Arefeh Sherafati, Aahana Bajracharya, Michael S Jones, Emma Speh, Monalisa Munsi, Chen-Hao P Lin, Andrew K Fishell, Tamara Hershey, Adam T Eggebrecht, Joseph P Culver, Jonathan E Peelle

2020-Current year OA Pubs

Traditional laboratory tasks offer tight experimental control but lack the richness of our everyday human experience. As a result, many cognitive neuroscientists have been motivated to adopt experimental paradigms that are more natural, such as stories and movies. Here we describe data collected from 58 healthy adult participants (aged 18-76 years) who viewed 10 minutes of a movie (The Good, the Bad, and the Ugly, 1966). Most (36) participants viewed the clip more than once, resulting in 106 sessions of data. Cortical responses were mapped using high-density diffuse optical tomography (first- through fourth nearest neighbor separations of 1.3, 3.0, 3.9, …

The Association Between Physical Activity, Sedentary Time, And Sleep With Risk Of Hepatocellular Carcinoma In Patients With Cirrhosis, Samuel Ma, Yossef Alsabawi, Fasiha Kanwal, Hao Duong, Laith Elserag, Amit G. Singal, Nicole E. Rich, Saira Khaderi, Sumeet K. Asrani, Hashem B. El-Serag, Aaron P. Thrift

School of Medicine Publications

Background: The majority of hepatocellular carcinoma (HCC) cases arise in patients with cirrhosis, with known major risk factors of hepatitis B (HBV) or C (HCV) infection, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). However, the impact of additional risk factors that act independently or jointly on the pathogenesis of HCC in cirrhosis patients is unknown. The aim of this study was to determine whether sleep, sedentariness, or physical activity levels play a role in the progression of cirrhosis to HCC.

Methods: We systematically collected data on sleep, sedentary time, and physical activity from the ongoing prospective …

Ezhip Boosts Neuronal-Like Synaptic Gene Programs And Depresses Polyamine Metabolism, Elham Hasheminasabgorji, Huey-Miin Chen, Taylor A Gatesman, Subhi Talal Younes, Gabrielle A Nobles, Farhang Jaryani, Heather Mao, Kwanha Yu, Benjamin Deneen, Wee Yong, Michael D Taylor, Sameer Agnihotri, Marco Gallo

Faculty, Staff and Students Publications

It is currently understood that the characteristic loss of the repressive histone mark H3K27me3 in PFA ependymoma and diffuse midline glioma (DMG) are caused by complementary mechanisms mediated by EZHIP and the oncohistone H3K27M, respectively. To support the complementarity of these mechanisms, rare H3K27M-negative DMGs express EZHIP. Interestingly, EZHIP is one of the few genes recurrently mutated in PFA. The significance of EZHIP mutations in PFA, and whether EZHIP has wider functions in addition to repression of H3K27me3 deposition, are not known. Here, we investigated the mutational landscape of EZHIP in pediatric brain tumors. We found that EZHIP mutations occur …

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi

School of Graduate Studies Faculty Publications

Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …

Aberrant Expression Of A Disintegrin And Metalloproteinase With Thrombospondin Motifs 13 (Adamts13) In Pancreatic Cancer Leads To Dichotomic Functions, Stephanie Allmang, Hagen R. Witzel, Anne Hausen, Simone Marquard, Christoph Eckert, Nicole Marnet, Nina Hörner, Philipp Mayer, Stefan Heinrich, Hien Dang, Wilfried Roth, Matthias M. Gaida

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers characterized by highly invasive growth into the surrounding peripancreatic fat tissue, where tumor cells can directly interact with adipocytes. Due to poor response to the currently available (radio)chemotherapies, there is an urgent need for advanced therapy concepts. The present study shows that ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a key factor in blood coagulation, is significantly overexpressed in human PDAC. Immunohistochemical analysis revealed that ADAMTS13 expression is associated with prolonged survival and negatively correlated with vascular density. In vitro and in vivo experiments demonstrate its partial …

Lipedema And Adipose Tissue: Current Understanding, Controversies, And Future Directions, Atefeh Rabiee

Pacific Faculty Work

Lipedema is a chronic disorder characterized by the symmetrical accumulation of subcutaneous adipose tissue, predominantly affecting women. Despite increasing recognition, the pathophysiological mechanisms underlying adipose tissue dysfunction in lipedema remain incompletely understood. This mini review combines current knowledge about adipose tissue biology in lipedema, highlighting recent discoveries, ongoing controversies, and future research directions. A comprehensive literature review was conducted focusing on adipose tissue-related research in lipedema with emphasis on pathophysiological mechanisms, cellular composition, and therapeutic implications. Recent studies reveal that lipedema adipose tissue exhibits distinct characteristics, including M2 macrophage predominance, stage-dependent adipocyte hypertrophy, progressive fibrosis, and altered lymphatic/vascular function. The …

Mutational Landscape And Clinical Impact Of Spen Mutations In Patients With Chronic Lymphocytic Leukemia, Priyatharsini Nirmalanantham, Andrés E Quesada, Anindita Ghosh, Pei Lin, Chi Y Ok, Richard K Yang, Hong Fang, Sofia Garces, Rashmi Kanagal-Shamanna, Sanam Loghavi, Mark J Routbort, Cameron Cheng Yin, Wang Wei, Sarah Pasyar, Roland Bassett, Siba El Hussein, Nitin Jain, Jan Burger, William G Wierda, Sa Wang, Carlos Bueso-Ramos, Keyur P Patel, Leonard Jeffrey Medeiros, Fatima Zahra Jelloul

Faculty, Staff and Student Publications

Background/objectives: NOTCH1 is frequently mutated in chronic lymphocytic leukemia (CLL) and is a marker of poor prognosis. In addition to NOTCH1, mutations in the NOTCH1 regulatory pathway including SPEN have been described in a limited number of CLL cases and others have suggested that these mutations are also associated with adverse patient outcomes Methods: In this study, 1617 CLL cases were assessed using targeted sequencing and a 29-gene panel and the results were correlated with prognosis.

Results: SPEN mutations were detected in 48 (2.9%) CLL patients: 92.4% were deleterious (frameshift or truncating nonsense mutations) and the remaining (7.6%) were …

Advancing Delirium Detection Through The Open Health Natural Language Processing Consortium And The Evolve To Next-Gen Accrual To Clinical Trials Network, Sunyang Fu, Min Ji Kwak, Jaerong Ahn, Zhiyi Yue, Shreyas Ranganath, Joseph R Applegate, Andrew Wen, Liwei Wang, Chenyu Li, Michele Morris, Kelly M Toth, Timothy D Girard, John D Osborne, Richard E Kennedy, Nelly-Estefanie Garduno-Rapp, Phillip Reeder, Justin F Rousseau, Chao Yan, You Chen, Mayur B Patel, Tyler J Murphy, Bradley A Malin, Chan Mi Park, Heling Jia, Sandeep Pagali, Allyson K Palmer, Jennifer St Sauver, Sunghwan Sohn, Elmer V Bernstam, Shyam Visweswaran, Yanshan Wang, Hongfang Liu

Faculty, Staff and Student Publications

Background: Delirium is often underdiagnosed in clinical practice and is not routinely coded for billing. While manual chart review can identify delirium, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) can analyze unstructured text in electronic health records (EHRs) to extract meaningful clinical information.

Methods: To support national integration of NLP for EHR-based delirium identification across different institutions, we launched the Delirium Interest Group within the national Evolve to Next-Gen Accrual to Clinical Trials (ENACT) NLP Working Group. This paper outlines our initial efforts to standardize, evaluate, and translate an NLP-based delirium detection model into the …

Distinct Tumor-Associated Macrophage Signatures Shape The Immune Microenvironment And Patient Prognosis In Renal Cell Carcinoma, Youngsoo Han, Aidan Shen, Cheng-Chi Chao, Lucas Yeung, Aliesha Garrett, Jianming Zeng, Satoru Kawakita, Jesse Wang, Zhaohui Wang, Alireza Hassani, Xiling Shen, Chongming Jiang

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and validated across independent RCC cohorts. Model performance was assessed through Kaplan-Meier survival plots, receiver operating characteristic (ROC) …

Distinguishing Syndromic And Nonsyndromic Cleft Palate Through Analysis Of Protein-Altering De Novo Variants In 818 Trios, Kelsey R Robinson, Sarah W Curtis, Justin E Paschall, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, David J Cutler, Michael P Epstein, Lord J J Gowans, Jacqueline T Hecht, Gary M Shaw, Lina Moreno Uribe, Jeffrey C Murray, Harrison Brand, Seth M Weinberg, Mary L Marazita, Kimberly F Doheny, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

De novo variants (DNs) are sporadically occurring variants found in an offspring but absent in both parents. DNs most commonly arise in the germline and are not under selective pressure; therefore, they may be enriched for disease-causing alleles. In fact, DNs have been implicated in multiple rare genetic disorders. Cleft palate (CP) is a craniofacial congenital anomaly occurring in ∼1 in 1,700 live births. Genome-wide association studies have found fewer than a dozen CP-specific loci, while exome and targeted sequencing studies in family-based and case-control cohorts often lack statistical power to conclusively identify causal variants. We therefore hypothesized that CP …