Life Sciences Commons^™

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 …

Quantitative Analysis Of Robustness-Based Versus Let-Based Optimization In Intensity-Modulated Proton Therapy For Pediatric Brain Tumors, Fariha Kabir Torsha, Gino Lim, Hadis Moazami Goudarzi, Radhe Mohan, David Grosshans, Wenhua Cao

Faculty, Staff and Student Publications

Purpose: To perform a quantitative analysis of the trade-off between robustness-based and linear energy transfer (LET)-based optimization of intensity-modulated proton therapy for anatomically challenging pediatric brain tumor cases.

Methods: Three pediatric brain tumor patients were included in this study. Three plans were generated for each case based on: (1) nominal optimization, without considering uncertainties and LET; (2) robust optimization, including proton range and patient setup uncertainties; and (3) LET optimization, considering increasing LET in the target and reducing LET in normal tissues. All plans were optimized with individually fine-tuned objective weighing to obtain highest achievable target coverage and meet dose …

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) …

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 …

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 …

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

Background

Objective

Methods

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

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 …

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 …

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 …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

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 …

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 …

Phase 1b Pilot Study Of Itacitinib With Alemtuzumab In Patients With T-Cell Prolymphocytic Leukemia, Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian

Faculty, Staff and Student Publications

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and …

First Report Of Response To Tarlatamab In A Patient With Histologic-Transformed Sclc From Alk-Rearranged Nsclc: Case Report, Kaiwen Wang, Ceylan Altintas Taslic, Patricia De Groot, Mitchell A Parma, Alvaro Guimaraes Paula, Melody Caranto, Komal Shah, Mukulika Bose, Cole Ruoff, Loukia G Karacosta, Lauren A Byers, Carl M Gay, Jianjun Zhang, John V Heymach, Bingnan Zhang

Faculty, Staff and Student Publications

Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.

Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Outcomes Of Therapy-Related Non-Core Binding Factor Acute Myeloid Leukemia With Venetoclax-Based Therapies, Jayastu Senapati, Jennifer Croden, Guillermo Garcia-Manero, Koichi Takahashi, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Nicholas James Short, Elias Jabbour, Fadi Haddad, Jennifer Marvin-Peek, Hussein A Abbas, Prithviraj Bose, Guilin Tang, Sanam Loghavi, Elizabeth J Shpall, Jeremy Ramdial, Uday R Popat, Richard E Champlin, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognosis in therapy‐related acute myeloid leukemia (T‐AML) remains poor, but understanding outcomes with venetoclax (VEN)‐based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T‐AML focusing on lower intensity therapy (LIT) VEN‐containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21–92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a TP53 mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC …

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 …

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.

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 …

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 …

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 …

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 ( …