Medicine and Health Sciences Commons^™

Digital Stress Scale (Dsc): Development And Psychometric Validation Of A Measure Of Stress In The Digital Age, Agathi Argyriadi, Dimitra Katsarou, Athina Patelarou, Kalliopi Megari, Evridiki Patelarou, Stiliani Kotrotsiou, Konstantinos Giakoumidakis, Shabnam Abdoola, Evangelos Mantsos, Efthymia Efthymiou, Alexandros Argyriadis

All Works

(1) Background: The integration of digital technologies such as electronic health records (EHRs), telepsychiatry, and communication platforms has transformed the mental health sector a lot compared to in previous years. While these tools enhance service delivery, they also introduce unique stressors. Despite growing concerns, there is no validated instrument specifically designed to measure the digital stress experienced by mental health professionals. (2) Methods: This study involved the development and psychometric validation of the Digital Stress Scale (DSC). The process included item generation through a literature review and qualitative interviews, expert panel validation, and a two-phase statistical evaluation. Exploratory Factor Analysis …

Author Reply, Cyprian Mostert

Population Health, East Africa

No abstract provided.

Comparison Between Acute Leukemia Screening Tube And Lineage-Specific Panels For The Diagnosis Of Acute Leukemia In Kenya, Nancy Okinda, Geoffrey Omuse, Elizabeth Kagotho, Douglas Munga

Pathology, East Africa

Purpose: Acute leukemia is a group of hematologic malignancies categorized according to the immature cells that proliferate and replace the normal bone marrow. Flow cytometry has emerged as a cornerstone in the diagnosis of hematologic malignancies. Staged analysis with a screening tube containing specific lineage markers determines the need for subsequent testing if there is an abnormal population (blasts). The specific lineage panels to be analyzed are determined depending on the positive markers in the screening tube. This study aimed to determine the agreement of diagnosis using the acute leukemia screening tube (ALST) and the lineage-specific panel.

Methods: This was …

Mtap Immunohistochemistry As A Surrogate Marker Of Cdkn2a Loss In Brain Tumors: A Meta-Analysis And Literature Review, Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted …

I2moe: Interpretable Multimodal Interaction-Aware Mixture-Of-Experts, Jiayi Xin, Sukwon Yun, Jie Peng, Inyoung Choi, Jenna L Ballard, Tianlong Chen, Qi Long

Faculty, Staff and Student Publications

Modality fusion is a cornerstone of multimodal learning, enabling information integration from diverse data sources. However, vanilla fusion methods are limited by

It Is Time We Include Leadership Education And Experiences In Mfm Training And Lifelong Learning, Cheryl A Moyer, Timothy R B Johnson

Faculty, Staff and Student Publications

No abstract provided.

Federated Target Trial Emulation Using Distributed Observational Data For Treatment Effect Estimation, Haoyang Li, Chengxi Zang, Zhenxing Xu, Weishen Pan, Suraj Rajendran, Yong Chen, Fei Wang

Faculty, Staff and Student Publications

Target trial emulation (TTE) aims to estimate treatment effects by simulating randomized controlled trials using real-world observational data. Applying TTE across distributed datasets shows great promise in improving generalizability and power but is always infeasible due to privacy and data-sharing constraints. Here we propose a Federated Learning-based TTE framework, FL-TTE, that enables TTE across multiple sites without sharing patient-level data. FL-TTE incorporates federated protocol design, federated inverse probability of treatment weighting, and a federated Cox proportional hazards model to estimate time-to-event outcomes across heterogeneous data. We validated FL-TTE by emulating Sepsis trials using eICU and MIMIC-IV data from 192 hospitals, …

Dynamic Few-Shot Prompting For Clinical Note Section Classification Using Lightweight, Open-Source Large Language Models, Kurt Miller, Steven Bedrick, Qiuhao Lu, Andrew Wen, William Hersh, Kirk Roberts, Hongfang Liu

Faculty, Staff and Student Publications

Objective: Unlocking clinical information embedded in clinical notes has been hindered to a significant degree by domain-specific and context-sensitive language. Identification of note sections and structural document elements has been shown to improve information extraction and dependent downstream clinical natural language processing (NLP) tasks and applications. This study investigates the viability of a dynamic example selection prompting method to section classification using lightweight, open-source large language models (LLMs) as a practical solution for real-world healthcare clinical NLP systems.

Materials and methods: We develop a dynamic few-shot prompting approach to classifying sections where section samples are first embedded using a transformer-based …

Non-Invasive Tools For Analysis Of Plasma Membrane Protein Topology In Living Cells, Daria Savenkova, Leysan Bulatova, Vera Skripova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane protein topology studies offer guidance to membrane protein structure, folding, and function, serving as a credible scaffold for designing site-directed mutagenesis and biochemical experiments, helping to identify functionally significant extracellular and intracellular regions, modeling three-dimensional structures, and building reliable mechanistic models. Membrane protein structure as a function of given lipid composition and physiological state of the cell is best probed in whole intact cells. A described simple and advanced immunofluorescence protocol applied to the transmembrane orientation of extramembrane domains permits a topology analysis of plasma membrane proteins in their native state in living unperturbed eucaryotic cells. The accessibility of …

Long Akap18 Isoforms Anchor Ubiquitin Specific Proteinases And Coordinate Calcium Reuptake At The Sarcoplasmic Reticulum, Taeyeop Park, Katherine Forbush, Yong Li, Oscar Vivas, Kacey J Rosenthal, Jerome Falcone, Cassandra J Wong, James E Bruce, Claudia Moreno, Carmen W Dessauer, John D Scott

Faculty, Staff and Student Publications

Subcellular targeting of signaling enzymes influences where and when various modes of intracellular communication operate. Macromolecular complexes of signal transduction and signal termination elements favor reversible control of repetitive processes. This includes adrenergic stimulation of excitation–contraction coupling in the heart. Long isoforms of A-kinase anchoring protein 18 (AKAP18γ and δ) modulate this process via regulation of calcium uptake into the sarcoplasmic reticulum through the Ca2+ATPase 2a (SERCA2a). AKAP18 proximity-proteomic screening in cardiomyocytes identifies networks for protein kinase A (PKA) and ubiquitin-specific proteinases (USPs). A 2′phosphoesterase domain on AKAP18 interfaces with the USP4 isoform at the Z bands of sarcomeres. PKA …

Bridging Cell Morphological Behaviors And Molecular Dynamics In Multi-Modal Spatial Omics With Morphlink, Jing Huang, Chenyang Yuan, Jiahui Jiang, Jianfeng Chen, Sunil S Badve, Yesim Gokmen-Polar, Rossana L Segura, Xinmiao Yan, Alexander Lazar, Jianjun Gao, Bing Yao, Michael Epstein, Linghua Wang, Jian Hu

Faculty, Staff and Student Publications

Multi-modal spatial omics data are invaluable for exploring complex cellular behaviors in diseases from both morphological and molecular perspectives. Current analytical methods primarily focus on clustering and classification, and do not adequately examine the relationship between cell morphology and molecular dynamics. Here, we present MorphLink, a framework designed to systematically identify disease-related morphological-molecular interplays. MorphLink has been evaluated across a wide array of datasets, showcasing its effectiveness in extracting and linking interpretable morphological features with various molecular measurements in spatial omics analyses. These linkages provide a transparent view of cellular behavior heterogeneity within tissue regions with similar cell type compositions, …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison B Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth F Sutton, Pamela M Simmons, George R Saade, Antonio Saad, Luis D Pacheco, Esther Park-Hwang, Antonina I Frolova, Ebony B Carter, Ai-Ris Y Collier, Daniel G Kiefer, Vincenzo Berghella, Rupsa C Boelig, Michal A Elovitz, Cynthia Gyamfi-Bannerman, Joseph R Biggio, Kara Rood, William A Grobman, Carrie Haverty, Morten Rasmussen

Faculty, Staff and Student Publications

Importance: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

Objective: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

Design, setting, and participants: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Practical Considerations For Using The Tite-Boin Design To Handle Late-Onset Toxicity Or Fast Accrual In Phase I Trials, Kai Chen, Ting-Yu Chen, Yiming Zhang, Ruitao Lin, Ying Yuan

Faculty, Staff and Student Publications

Conducting phase I trials is particularly challenging when dealing with late-onset dose-limiting toxicity (DLT) or when patient accrual is rapid relative to the DLT assessment window. In such cases, a new cohort may be ready for enrollment before the DLT assessments are complete for the current cohort, complicating dose assignment decisions. The time-to-event Bayesian optimal interval (TITE-BOIN) design was developed to address this issue by enabling real-time dose assignment for new cohorts, even when some enrolled patients' DLT data are still pending. This design has been increasingly adopted in practice. Upon reviewing trial protocols utilizing TITE-BOIN, we observed considerable variation …

Myh11 Rare Variant Augments Aortic Growth And Induces Cardiac Hypertrophy And Heart Failure With Pressure Overload, Zhen Zhou, Kgosi Hughes, Nisha Saif, Hyoseon Kim, Michael P Massett, Mingjie Zheng, Alana C Cecchi, Dongchuan Guo, David R Murdock, Ping Pan, Jelita S Clinton, Jun Wang, John M Greally, Dianna M Milewicz

Faculty, Staff and Student Publications

Smooth muscle cell-specific myosin heavy chain, encoded by MYH11, is selectively expressed in smooth muscle cells (SMCs). Pathogenic variants in MYH11 predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including MYH11 p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate Myh11E1892D/E1892D mice. Wild-type (WT) and mutant mice underwent cardiovascular phenotyping with and without transverse aortic constriction (TAC). Myh11E1892D/E1892D and WT mice displayed …

Incomplete Toxicity Reporting And Use Of Toxicity-Minimizing Language In Phase Iii Oncology Trials, Avital M Miller, Adina H Passy, Alexander D Sherry, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Gabrielle S Kupferman, Esther J Beck, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: This study aimed to determine complete toxicity reporting (CTR), and the use of subjective toxicity-minimizing language (TML) among phase III oncology trials.

Methods: Two-arm superiority-design phase III oncology trials published from 2002 to 2020 were reviewed for toxicity data. CTR was defined as reporting total adverse events (TAEs), total serious adverse events (SAEs), total deaths, and study therapy discontinuations because of toxicity. Guideline concordance was defined according to guidelines published in the BMJ (defined as reporting total SAEs, total deaths, and study therapy discontinuations because of toxicity). TML was defined as a set of terms that subjectively downplay the …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Involved But Not Essential: Cognitive Activity In Periventricular Nodules And Neuropsychological Outcomes Following Their Ablation, Yosefa A Modiano, Oscar Woolnough, Ryan M Mccormack, Kathryn Snyder, Ellery Wheeler, Samden D Lhatoo, Nuria Lacuey, Sandipan Pati, Katherine Harris, Jay Gavvala, Jessica A Johnson, Nitin Tandon

Faculty, Staff and Student Publications

Objective: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development with high rates of epilepsy. The extent to which nodules participate in normal cerebral functions in addition to pathological processes is unclear. The authors assessed the functional utility (i.e., cognitive impacts) of surgically ablated epileptogenic PVNH tissue via comprehensive neuropsychological testing.

Methods: The sample included 32 patients with PVNH who underwent presurgical neuropsychological evaluation and a subsample of 16 patients who underwent MR-guided laser interstitial thermal therapy (MRgLITT) of nodules, with postsurgical neuropsychological testing. In 11 patients in whom intracranial recordings were performed, reading and naming tasks were tested …

Diagnostic Guidance For Chronic Complex Regional Pain Syndrome Type I And Type Ii From The American Society Of Interventional Physicians (Asipp), Christopher Gharibo, Miles Day, Steve M Aydin, Alan D Kaye, Salahadin Abdi, Sudhir Diwan, Lisa V Doan, Danielle Feng, Kris Ferguson, Kirolos Georges, Andrew Kaufman, Nebojsa Nick Knezevic, Sean Li, Franzes A Liongson, Devi Nampiaparampil, Annu Navani, Mahendra Sanapati, Michael E Schatman, Amol Soin, Peter S Staats, Giustino Varrassi, Jing Wang, Laxmaiah Manchikanti

Faculty, Staff and Student Publications

Background: Complex Regional Pain Syndrome (CRPS) is a challenging and often disabling condition marked by persistent pain, most commonly in a limb following injury or surgery. It presents with a wide array of symptoms, including intense pain, swelling, alterations in skin color and temperature, motor dysfunction, and trophic changes such as skin and tissue atrophy. While the precise cause of CRPS is not fully understood, it is thought to stem from abnormal nervous system activity, leading to heightened pain sensitivity and inflammatory responses. A thorough understanding of CRPS is essential for accurate diagnosis, effective treatment, and enhancing patients' quality of …

Bayesian Inference Of Fitness Landscapes Via Tree-Structured Branching Processes, Xiang Ge Luo, Jack Kuipers, Kevin Rupp, Koichi Takahashi, Niko Beerenwinkel

Faculty, Staff and Student Publications

Motivation: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees.

Results: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …

Targeting Cdk2 And Other Novel Cell Cycle Targets For Breast Cancer Therapy, Mei-Kuang Chen, Linjie Luo, Nicole Massoumi, Khandan Keyomarsi

Faculty, Staff and Student Publications

Introduction: The dysregulation of cyclin-dependent kinases (CDKs) is a key driver of cancer progression, making them attractive therapeutic targets. In CDK4/6 inhibitor (CDK4/6i)-resistant breast cancer, targeting CDK2 offers a promising approach. CDK2 is frequently hyperactivated due to cyclin E1 overexpression or retinoblastoma protein loss, acting as a mechanism that sustains proliferation despite CDK4/6 inhibition. CDK2 inhibitors (CDK2i) show strong anti-tumor activity, particularly in combination with CDK4/6i or immune checkpoint inhibitors.

Areas covered: This review explores the biological roles of CDK2 and its regulatory mechanisms. The review highlights the latest advancements in CDK2i, their mechanisms of action, and their potential in …

Institutional Learning Curve And Factors Of Prolonged Operation Time Of Robotic Distal Pancreatectomy: An Analysis Of An Initial 117 Cases, Yuki Hirata, Laura Prakash, Jess Maxwell, Rebecca Snyder, Michael Kim, Hop Tran Cao, Ching-Wei D Tzeng, Jefferey E Lee, Matthew H G Katz, Naruhiko Ikoma

Faculty, Staff and Student Publications

Background: The granular methods by which centers can safely implement and effectively expand robotic distal pancreatectomy (RDP), including those related to appropriate patient selection during the learning curve period, remain unclear. This study aimed to verify that our strategic robotic surgical oncology program effectively implemented RDP as standard practice and to identify factors associated with prolonged operation time.

Materials and methods: We performed a detailed analysis of the intraoperative and short-term outcomes of consecutive patients (October 2018-September 2023) undergoing RDP at our center, beginning with the first patient in our program. Operation time was analyzed using a cumulative sum chart …

Long-Term Cytoreduction Outcomes With Or Without Heated Intraperitoneal Chemotherapy For Colorectal Peritoneal Metastases, Michael G White, Paula Marincola Smith, Neal Bhutiani, Beth Helmink, Norman Galbraith, Scott Kopetz, Michael Overman, Paul Mansfield, Keith Fournier, Abhineet Uppal

Faculty, Staff and Student Publications

Background: Patients with peritoneal metastases from colorectal adenocarcinoma (CRC) benefit from cytoreductive surgery (CRS). However, the role of heated intraperitoneal chemotherapy (HIPEC) remains unclear. We studied associations between HIPEC, peritoneal disease-free survival (PDFS), and overall survival (OS) in patients with CRC undergoing CRS.

Study design: All patients with CRC undergoing CRS between 2008 and 2023 were retrospectively identified at our center. Patient clinicodemographic factors were determined by chart review. OS and PDFS were evaluated using the Kaplan-Meier method. Associations between clinical factors and survival were determined using Cox proportional hazard models.

Results: A total of 147 patients were identified with …

Author Correction: Autologous T Cell Therapy For Prame+ Advanced Solid Tumors In Hla-A*02+ Patients: A Phase 1 Trial, Martin Wermke, Dejka M Araujo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten

Faculty, Staff and Student Publications

No abstract provided.

Effectiveness Of Allopurinol On Uric Acid And Pediatric Chronic Kidney Disease Severity In The Chronic Kidney Disease In Children Study., Derek K. Ng, Matthew B. Matheson, George J. Schwartz, Katherine E. Kurgansky, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE & OBJECTIVE: Clinical trials have shown that serum uric acid reduction does not slow chronic kidney disease (CKD) progression in adults, but it is uncertain whether these findings apply to children.

STUDY DESIGN: An observational cohort study.

SETTING & POPULATION: The Chronic Kidney Disease in Children cohort with participants who initiated allopurinol with a comparison group matched on age, sex, uric acid, CKD diagnosis, estimated glomerular filtration rate (eGFR), and proteinuria.

EXPOSURE: Allopurinol initiation.

OUTCOMES: Uric acid, eGFR, and proteinuria before and after initiation, and longitudinal changes over time.

ANALYTICAL APPROACH: Allopurinol initiators were matched to noninitiators at a …

Pathologist-Read Vs Ai-Driven Assessment Of Tumor-Infiltrating Lymphocytes In Melanoma, Thazin N Aung, Matthew Liu, David Su, Saba Shafi, Ceren Boyaci, Sanna Steen, Nikolaos Tsiknakis, Joan Martinez Vidal, Nigel Maher, Goran Micevic, Samuel X Tan, Matthew D Vesely, Saeed Nourmohammadi, Yalai Bai, Dijana Djureinovic, Pok Fai Wong, Katherine Bates, Nay N N Chan, Niki Gavirelatou, Mengni He, Sneha Burela, Robert Barna, Martina Bosic, Konstantin Bräutigam, Irineu Illabochaca, Zhou Chenhao, Joao Gama, Bianca Kreis, Reka Mohacsi, Nir Pillar, Joao Pinto, Christos Poulios, Maria Angeliki Toli, Evangelos Tzoras, Yadriel Bracero, Francesca Bosisio, Gábor Cserni, Alis Dema, Francesco Fortarezza, Mercedes Solorzano Gonzalez, Irene Gullo, Francisco Javier Queipo Gutiérrez, Ezgi Hacihasanoglu, Viktor Jovic, Bianca Lazar, Maria Olinca, Christina Neppl, Rui Caetano Oliveira, Federica Pezzuto, Daniel Gomes Pinto, Vanda Plotar, Ovidiu Pop, Tilman Rau, Kristijan Skok, Wenwen Sun, Ezgi Dicle Serbes, Wiebke Solass, Olga Stanowska, Marcell Szasz, Krzysztof Szymonski, Franziska Thimm, Danielle Vignati, Alon Vigdorovits, Victor Prieto, Tobias Sinnberg, James Wilmott, Shawn Cowper, Jonathan Warrell, Yvonne Saenger, Johan Hartman, Jasmine Plummer, Iman Osman, David L Rimm, Balazs Acs

Faculty, Staff and Student Publications

Importance: Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin-stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important.

Objective: To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods.

Design, setting, and participants: This multioperator, global, multi-institutional prognostic study compared TIL scoring reproducibility between traditional pathologist-read methods and an artificial intelligence (AI)-driven approach. The …

Adtnorm: Robust Integration Of Single-Cell Protein Measurement Across Cite-Seq Datasets, Ye Zheng, Daniel P Caron, Ju Yeong Kim, Seong-Hwan Jun, Yuan Tian, Florian Mair, Kenneth D Stuart, Peter A Sims, Raphael Gottardo

Faculty, Staff and Student Publications

Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm, a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations …

Spontaneous Tumor Regression And Immunotherapy Response Demonstrate Clonal T-Cell Expansion In Merkel Cell Carcinoma, Patrick Hallaert, John W Roman, Mairead Baker, Natasha T Hill, Jennifer L Marte, James L Gulley, Nicholas Logemann, Courtney W Hudgens, Alexandre Reuben, Isaac Brownell

Faculty, Staff and Student Publications

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is responsive to immune checkpoint inhibitors (ICI). On rare occasion, MCC spontaneously regresses. It is speculated that this regression occurs when biopsy-induced antigen shedding precipitates an immune response. Here, we demonstrate the activation of an adaptive immune response in a patient whose tumor underwent spontaneous regression after biopsy. To evaluate the tumor immune microenvironment during regression, we performed quantitative immunohistochemical analysis and T-cell receptor (TCR) sequencing. Relative to baseline, the regressing tumor showed evidence of an activated cytotoxic T-cell response together with increased TCR clonality, greater representation …

Feasibility Of Monte Carlo-Based Patient-Specific Quality Assurance In 15 Tesla Magnetic Resonance-Guided Online Adaptive Radiotherapy: A Multi-Institutional Study, Ruiqi Li, Yao Zhao, Jingying Lin, Tsuicheng Chiu, Weiguo Lu, Jinzhong Yang, Mu-Han Lin

Faculty, Staff and Student Publications

Introduction: To evaluate the feasibility of Monte Carlo (MC)-based patient-specific quality assurance (PSQA) for MR-guided online adaptive radiotherapy and to explore the potential to eliminate the post-delivery measurement-based PSQA.

Material and methods: A total of 113 cases from two institutions, treated on MR-Linac machines, were included in the study. A customized GPU-accelerated, Monte Carlo-based secondary dose verification software (ART2Dose) was developed and integrated into the QA workflow, accounting for a 1.5 Tesla magnetic field. PSQA included ArcCheck (AC) delivery QA and online MC calculation-based QA. Reference plans underwent offline validation with AC and MC, while adapt-to-shape (ATS) plans were processed …

The Landmark Series: Therapeutic Cancer Vaccine Strategies For Cold Tumors, Alex B Blair, Lei Zheng, Kevin C Soares

Faculty, Staff and Student Publications

Immunologically cold tumors present a significant challenge in cancer treatment due to their limited baseline immune infiltration and resistance to immunotherapy. Cancer vaccines offer a promising strategy to overcome this barrier by introducing high-quality, tumor-relevant antigens that can stimulate an effective anti-tumor immune response. Therapeutic cancer vaccines are being explored in the neoadjuvant, adjuvant, and minimal residual disease contexts to enhance immune activation and promote immune cell infiltration and function, with the goal to eradicate malignant cells and improve patient survival. Critical hurdles remain in optimizing antigen selection, determining the most effective vaccine formulations, and defining the ideal clinical setting …