Digital Commons Network^™

Are Fewer Damage Control Laparotomies Associated With A Decrease In The Rate And Severity Of Surgical Site Infections?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, William D Rieger, Renee W Green, John A Harvin, Lillian S Kao

Faculty, Staff and Student Publications

Background: Damage control laparotomy (DCL) rates have declined and remained low. Given DCL's association with surgical site infections (SSIs), we hypothesize that SSI rates and severity, as per Clavien-Dindo (CD) classification, have decreased concurrently.

Patients and methods: A retrospective study was performed on patients (≥16 y) who underwent trauma laparotomy from January 2011 to December 2020. Patients who survived ≤48 hours were excluded. Data were divided into period 1 (January 2011-December 2015, DCL rates declined) and period 2 (January 2016-December 2020, low DCL rates were sustained). SSIs were defined as per the Centers for Disease Control and Prevention, and severity …

Cardiometabolic Parameter Change By Weight Regain On Tirzepatide Withdrawal In Adults With Obesity: A Post Hoc Analysis Of The Surmount-4 Trial, Deborah B Horn, Bruno Linetzky, Melanie J Davies, Luke J Laffin, Hui Wang, Madhumita A Murphy, Sarah Zimner-Rapuch, Eva Lau, Avigdor D Arad, Clare J Lee

Faculty, Staff and Student Publications

Importance: In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown.

Objective: To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide.

Design, setting, and participants: This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025.

Interventions: After …

Role Of Childhood Trauma In Interoception And Alexithymia In Schizophrenia, Samantha Narvaez, Krista Wisner, Alina Siatka, L Elliot Hong, Joshua Chiappelli

Faculty, Staff and Student Publications

Childhood trauma (CT) is a notable risk factor for schizophrenia. Separately, CT has been associated with alexithymia, referring to difficulties in identifying and describing one's own feelings, as well as disturbed interoception, referring to difficulties sensing and responding to signals that originate from within the body. Both self-perception impairments have been observed in schizophrenia; however, the role of CT in these observations in schizophrenia is unclear. To address this gap, interoception was assessed using the Multidimensional Assessment of Interoceptive Awareness (MAIA), alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20), and CT was measured using the Childhood Trauma Questionnaire (CTQ) …

Dopamine Agonist Therapy Induced Fatal Pneumocephalus In Giant Prolactinoma, Archana M H, Anurag Ranjan Lila, Manjiri Karlekar, Saba Samad Memon, Rohit Barnabas, Tushar Bandgar

Faculty, Staff and Student Publications

We report a man in the fifth decade of his life with an invasive giant prolactinoma (size: 7.3 cm; serum prolactin 56820 ng/mL [SI: 2470.4 nmol/L], reference range, 5-25 ng/mL [SI: 0.22-1.09 nmol/L]) who presented with hypogonadism and headache. Dopamine agonist (DA) cabergoline (0.25 mg twice weekly) was initiated, and serum prolactin levels reached 3941 ng/mL (SI: 171.3 nmol/L) after 2 doses. Two weeks later, he developed acute symptoms of headache, vomiting, and drowsiness associated with cerebrospinal fluid rhinorrhea. He presented to the casualty after 48 hours of the onset of these acute symptoms in an altered state. Neuroimaging demonstrated …

Cultural Influences On Camouflaging And Autistic Burnout: Examining The Experiences Of Latino Autistic Young Adults, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study explored the relationship between camouflaging, autistic burnout, and cultural factors in Latino young adults with autism spectrum disorder (ASD). While autistic burnout and camouflaging have been widely studied in general ASD populations, limited research has focused on Latino individuals, who may experience unique pressures due to cultural values such as collectivism, familism, and traditional gender roles. Participants (N = 56) from the ¡Iniciando! la Adultez therapy program completed measures assessing burnout, camouflaging, acculturation, and cultural values. Results indicate that participants reported moderate to high levels of autistic burnout, with the highest levels observed in heightened self-awareness …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Participant Retention In A Prospective Multicenter Cohort Of Participants With Pancreatitis And Factors Associated With Attrition, Radmila Choate, Jun Xu, Jeffrey J Easler, Samuel Han, Anna E Phillips, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Liang Li, Darwin L Conwell, Dhiraj Yadav

Faculty, Staff and Students Publications

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP).

Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate …

Rethinking The Centrality Of Brain Areas In Understanding Functional Organization, Benjamin Yost Hayden, Sarah R Heilbronner, Seng Bum Michael Yoo

Faculty, Staff and Students Publications

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Identification Of Raptor And Gli1 As Usp37 Substrates Highlight Its Context-Specific Function In Medulloblastoma Cells, Ashutosh Singh, Donghang Cheng, Amanda R Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.

Melody: Mediation Analysis In Logistic Regression For High-Dimensional Mediators And A Binary Outcome, Sunyi Chi, Xingyu Li, Peng Wei, Xuelin Huang

Faculty, Staff and Student Publications

Mediation analysis is a pivotal tool for elucidating the indirect effect of an environmental factor or treatment on disease through potentially high‐dimensional omics data, such as gene expression profiles. However, traditional mediation analysis methods tailored for binary outcomes often rely on the rare disease assumption in logistic regression and provide inadequate measures of total mediation effect when multiple mediators have effects in different directions. In this paper, we develop a MEdiation analysis framework in LOgistic regression for high‐Dimensional mediators and a binarY outcome (MELODY). It leverages a second‐moment‐based measure analogous to the ��2 for linear models to quantify the total …

Tumour-Brain Crosstalk Restrains Cancer Immunity Via A Sensory-Sympathetic Axis, Haohan K Wei, Chuyue D Yu, Bo Hu, Xing Zeng, Hiroshi Ichise, Liang Li, Yu Wang, Ruiqi L Wang, Ronald N Germain, Rui B Chang, Chengcheng Jin

Faculty, Staff and Student Publications

Body–brain communication has emerged as a key regulator of tissue homeostasis1–5. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes6–8. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity. Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional …

The Pandemic Effect: Secondary Impact On The Diagnosis Of Clinically Significant Congenital Heart Disease And Role Of Deprivation Index, Cassandra Campbell, Kristin Wyckoff, Ronak Naik, Nithya Swaminathan, Salima Ahmed Bhimani, Jason Johnson, Vijaya Joshi, Ranjit Philip

Faculty, Staff and Student Publications

We sought to determine the impact of the COVID-19 on prenatal diagnosis (PND) of clinically significant congenital heart disease (CHD) and the role of socioeconomic status (SES), complexity of diagnosis, and proximity to advance testing. This single-center retrospective study evaluated 2 eras of infants (COVID (born July 1, 2020–July 31, 2023) and pre-COVID (born June 1, 2017–July 1, 2020) who had cardiac surgery in the first year of life. 512 infants, 292 in pre-COVID era and 220 in COVID era with no significant difference in the rate of prenatal care (PNC) or PND in the COVID era (88%/42%) versus pre-COVID …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

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Objective

Methods

Venous Thromboembolism In Aggressive B-Cell Lymphoma Patients Treated With Cd19 Car-T Therapy: Single-Institution Study, Neha Venkatesh, Kevin Milligan, Julia Parrish, Yun Qing, Ryan Sun, Paolo Strati, Jeremy Ramdial, Amy Ayers, Sairah Ahmed, Cristhiam Rojas Hernandez

Faculty, Staff and Student Publications

Background: Large B-cell lymphomas (LBCLs) are a common subtype of non-Hodgkin lymphomas. CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized LBCL treatment, with high remission rates but also significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolism (VTE) in CAR-T therapy patients is understudied.

Objective: This study aims to determine the incidence and characteristics of acute VTE in LBCL patients treated with CAR-T therapy and identify baseline clinical features associated with VTE. Methods: We retrospectively reviewed 172 adult LBCL patients treated with CAR-T therapy from January 2018 to November 2019 at MD …

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Leveraging Large Language Models For Heuristic Usability Assessment Of Medical Software: Insights With The Radiation Planning Assistant, Laurence E Court, Jacobus Smit, Lourens Strauss, William Shaw, Andrea Marais, Christoph Trauernicht, Nanette Joubert, Elaine Smith, Shona Badre, Graeme L Lazarus, Thekiso Khotle, Lauren Netherton, Wanda Van Heerden, Carlos Cardenas, Monica Serban, Jan Seuntjens, Christine V Chung, Pavel Govyadinov, Meena Khan, Saurabh Nair, Tucker Netherton, Lifei Zhang

Faculty, Staff and Student Publications

Background: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

Methods: ChatGPT …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Can Patients With Recurrent Or Primary Squamous Cell Carcinoma Of The Anus In A Previously Irradiated Pelvis Receive Definitive Reirradiation, Jordan Mcdonald, Ethan P Damron, Prajnan Das, Eugene J Koay, Ethan B Ludmir, Bruce D Minsky, Sonal S Noticewala, Grace L Smith, Craig Messick, Van K Morris, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.

Methods and materials: Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously …

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud De La Fouchardière, Alexander J Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

Faculty, Staff and Student Publications

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

A Comparative Study Of Statistical Methods For Identifying Differentially Expressed Genes In Spatial Transcriptomics, Yishan Wang, Chenxuan Zang, Ziyi Li, Charles C Guo, Dejian Lai, Peng Wei

Faculty, Staff and Student Publications

Spatial transcriptomics (ST) provides unprecedented insights into gene expression patterns while retaining spatial context, making it a valuable tool for understanding complex tissue architectures, such as those found in cancers. Seurat, by far the most popular tool for analyzing ST data, uses the Wilcoxon rank-sum test by default for differential expression analysis. However, as a nonparametric method that disregards spatial correlations, the Wilcoxon test can lead to inflated false positive rates and misleading findings. This limitation highlights the need for a more robust statistical approach that effectively incorporates spatial correlations. To this end, we propose a Generalized Estimating Equations (GEE) …

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Tbr2-Dependent Parallel Pathways Regulate The Development Of Distinct Iprgc Subtypes, Takae Kiyama, Ching-Kang Chen, Halit Y Altay, Yu-Jiun Chen, Leviette Sigala, Dan Su, Steven Eliason, Brad A Amendt, Chai-An Mao

Faculty, Staff and Student Publications

The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …