Medicine and Health Sciences Commons^™

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Genetic Architecture Of N-Terminal Pro-B-Type Natriuretic Peptide In A Multiancestry Study Population, Naman S Shetty, Akhil Pampana, Mokshad Gaonkar, Amrita Nayak, Harshvir S Bal, Nirav Patel, Nehal Vekariya, J Gustav Smith, Alanna C Morrison, Bing Yu, Bruce M Psaty, Eric Boerwinkle, James S Floyd, Jerome I Rotter, Kent D Taylor, Leslie A Lange, Marguerite R Irvin, Mary Cushman, Stephen S Rich, Ramachandran S Vasan, Thomas J Wang, Xiuqing Guo, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

Background: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

Methods: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences …

Bispectral Index-Guided Anesthesia For Older Patients Having Noncardiac Surgery: A Randomized Multicenter Trial, Li Zhou, Lin Ding, Hui Yang, Chengyu Li, Zhangsheng Yu, Wei Ma, Qiuyu Chen, Yanzhuo Zhang, Yong Li, Qingxiang Mao, Minghua Cheng, Gu Gong, Enqin Wang, Cunming Liu, Wei Hao, Hong Li, Changlin Chen, Yaling Fan, Zhenbo Su, Xiaoli Cai, Xiaole Zhang, Zhi Li, Bing Zhang, Yi Li, Chunxiu Jiang, Qinqin Yin, Jiali Jiao, Daniel I Sessler, Qian Li, Jin Liu

Faculty, Staff and Student Publications

Background: Older surgical patients are at risk because of age-related physiologic decline and comorbidities. Some guidelines recommend Bispectral Index (BIS; Medtronic, USA) monitoring to optimize anesthetic depth, but robust evidence supporting improved outcomes is lacking.

Methods: A randomized, multicenter, double-blind trial was conducted across 21 tertiary-care hospitals in China (March 17, 2015, to February 5, 2022). Patients aged 65 yr or older scheduled for elective noncardiac surgery (American Society of Anesthesiologists [ASA] Physical Status I to IV) were randomized 1:1 to BIS-guided or routine anesthetic management. In patients assigned to BIS guidance, hypnotic depth was adjusted to maintain BIS between …

Examination Of Traffic Safety In Neighborhoods Associated With Active Commuting To School In Austin, Texas, Kathryn G Burford, Deborah Salvo, Harold W Kohl, Leigh Ann Ganzar, Cici X Bauer, Eugen Resendiz, Yuzi Zhang, Deanna M Hoelscher

Faculty, Staff and Student Publications

Background: Only 10% of US children participate in active commuting (walking and bicycling) to school (ACS). Parental concerns related to traffic are a primary barrier to ACS, yet no studies have assessed these concerns together with neighborhood traffic safety-related features. This study examined the associations between traffic safety-related features in neighborhoods and ACS among school-age children in Austin, Texas.

Methods: This cross-sectional analysis utilized pre-COVID-19 baseline data (2019-2020) of parent-child dyads enrolled in the Safe TRavel Environment Evaluation in Texas Schools study. ACS, traffic safety-related features in the neighborhood (sidewalk availability, safe road crossings, traffic safety, traffic speed, and safety …

Cellstaar: Incorporating Single-Cell-Sequencing-Based Functional Data To Boost Power In Rare Variant Association Testing Of Noncoding Regions, Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li, Hufeng Zhou, Nicholette D Palmer, Donna K Arnett, John Blangero, Eric Boerwinkle, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne Curran, Ravindranath Duggirala, Myriam Fornage, Nora Franceschini, Misa Graff, Charles Gu, Xiuqing Guo, Jiang He, Nancy Heard-Cosa, Lifang Hou, Yi-Jen Hung, Rita R Kalyani, Sharon L R Kardia, Eimear Kenny, Charles Kooperberg, Brian G Kral, Leslie Lange, Dan Levy, Changwei Li, Simin Liu, Donald Lloyd-Jones, Ruth J F Loos, Ani W Manichaikul, Lisa Warsinger Martin, Rasika Mathias, Ryan L Minster, Braxton D Mitchell, Josyf C Mychaleckyj, Take Naseri, Kari North, Jeff O'Connell, James A Perry, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Alex P Reiner, Stephen S Rich, Jennifer A Smith, Brian Spitzer, Hua Tang, Kent D Taylor, Russell Tracy, Satupa'itea Viali, Lisa Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Xihong Lin

Faculty, Staff and Student Publications

Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR …

Volumetric Buccal Bone Alterations At Immediate Implant Sites With Or Without Soft Tissue Augmentation: A 6-Month Assessment, Mary Jung, Duong Tran, Chi-Ching Chang, Sung K Kim, Yosuke Tsukiboshi, Seiko Min, Srinivas Ayilavarapu, Chun-Teh Lee

Faculty, Staff and Student Publications

Background: This study is part of a randomized controlled trial investigating the impact of soft tissue augmentation (STA) using subepithelial connective tissue graft (SCTG) (immediate implant with subepithelial connective tissue graft [ICT] group) or acellular dermal matrix (ADM) (immediate implant with acellular dermal matrix [IAD] group) versus no STA (control) on the clinical outcomes following immediate implant placement (IIP). This study aimed to investigate volumetric buccal bone dimensional changes at immediate implant sites 6 months after the surgery.

Methods: Forty-five patients requiring extraction of a maxillary anterior tooth or premolar and randomly assigned to one of the three groups were …

Ex Vivo Comparative Analysis Of Retrievability Among Four Calcium Silicate-Based Sealers For Regaining Apical Patency, Darian Shomali, Timothy Kirkpatrick, Sang Won Kwak, Hyeon-Cheol Kim, Ji Wook Jeong

Faculty, Staff and Student Publications

Objectives: : Efficient retrievability is a key requirement for endodontic sealers. This study evaluated the retrievability of four different calcium silicate-based sealers (CSS).

Methods: A total of 153 single-rooted human teeth with straight canals were decoronated to a standardized working length of 12 mm. The canals were negotiated to working length using K files up to size 15/.02, followed by rotary instrumentation up to 35/.04, 2 mm short of working length. The teeth were randomly assigned to five groups: NeoSEALER Flo (NEO; Avalon Biomed), Ceraseal (CS; Meta Biomed), Endosequence BC Sealer (BC; Brasseler USA), AH Plus Bioceramic Sealer (AHB; Dentsply …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Development And Implementation Of An Mri-Only Simulation, Planning, And Treatment Workflow For Prostate Radiotherapy Using Synthetic Ct On Mr-Linac, Reza Reiazi, Yao Ding, Sarath Vijayan, Jinzhong Yang, Ergys Subashi, Yao Zhao, Belinda M Lee, Hunter L Emory, Vi T Dinh, Greg L Swiedom, Jie Deng, Mu-Han Lin, Peter Balter, Rajat J Kudchadker, Elaine E Cha, Seungtaek Choi, Yusung Kim, Eun Young Han, Surendra Prajapati

Faculty, Staff and Student Publications

Purpose: We evaluated the feasibility of a magnetic resonance (MR)-only simulation, planning, and treatment (MROSPT) workflow for prostate cancer patients using synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) data. By validating sCT-based dose calculations, we aimed to streamline radiotherapy workflows, eliminate the need for CT simulation, and enable reliable clinical implementation of MR-based radiotherapy for MR-linac (MRL).

Methods: We developed a comprehensive workflow encompassing the entire process from initial consultation to treatment delivery. After developing the workflow, a retrospective dosimetric validation study was performed on nine men with prostate cancer. They underwent CT and MRI simulations, and …

Inferring High-Fat Dietary Patterns From Electronic Health Record Data Using Machine Learning, Ya-Yun Yeh, Hsin-Yueh Lin, Jingchuan Guo, Ramon C Sun, Sizun Jiang, Jiang Bian, Hao Dai

Faculty, Staff and Student Publications

Objectives: Electronic health records (EHRs) rarely capture dietary detail, limiting diet-disease research. We aimed to develop machine learning (ML) computable phenotypes to identify high-fat diet (HFD) using variables typically available in EHRs.

Materials and methods: We used National Health and Nutrition Examination Survey (NHANES) 1999-2020 data, where 24-h dietary recall served as ground truth. Dietary fat intake was summarized into a score (0-30) based on percent energy from fat, carbohydrate, and protein; lower scores indicated HFD. We defined HFD at cutoffs of 10, 15, and 20, and trained ML models (Extreme Gradient Boosting, logistic regression, random forest) using EHR-compatible variables …

Implanting Microelectrode Arrays In The Bottom Of The Central Sulcus Targeting Somatosensory Area 3a For Restoration Of Proprioception, Tyler R Johnson, Sarah Moralle, Ziling Luo, Dawn M Taylor

Faculty, Staff and Student Publications

Objective: The long-term goal of this work is to develop a sensorimotor brain-machine interface (BMI) in which intended movements are decoded from the motor cortex and proprioceptive feedback is delivered via intracortical microstimulation of Brodmann's area 3a. A vital step toward this goal is to demonstrate in rhesus macaques a novel surgical approach for the precise and safe implantation of custom-length microelectrode arrays into area 3a at the bottom of the central sulcus.

Methods: Preoperative planning combined high-resolution 7-T MR and CT imaging to generate 3D models of the cortices of 2 subjects. These models were used to fabricate 3D-printed …

Hootation: A Gui And Api Library For Ontology Validation And Verbalization., Muhammad Amith, Xubing Hao, Warren Manuel, Manqi Li, Shun Rao, Kirk Roberts, Hua Xu, Yang Gong, Frank Manion, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Ontology verbalization refers to the process of translating formal axioms into natural language expressions. The primary objective is to facilitate the review and validation of ontology content by subject matter experts without requiring extensive technical expertise. While previous approaches based on templates or controlled grammar have been effective, they often face limitations in scalability, fluency, and adaptability. To address these issues, we developed Hootation, an open-source software system that supports ontology verbalization through both a graphical user interface and an API library. The tool implements rule-based translation of OWL2 axioms and further incorporates optional Large Language Model (LLM) components for …

Visit-Level Quality Measurement Reveals Missed Opportunities And Overuse In Preventive Oral Health Care, Bunmi Tokede, Suhasini Bangar, Swaroop Gantela, Ryan Brandon, Alfa Yansane, Donald B Rindal, Don Worley, Joel White, Joanna Mullins, Ana Neumann, Todd Johnson, Nicholas Skourtes, Gregory Olson, Janelle Urata, Heather Weidner, Katie Lamberger, Aaron Truong, Heiko Spallek, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: Traditional annual dental quality measures fail to capture real-time care delivery and can mask critical gaps in patient-specific treatment. The authors developed and implemented visit-level adaptations of established caries quality measures to enable actionable, point-of-care assessment.

Methods: The authors conducted a retrospective analysis of 1.09 million dental visits across 400,000 patients (2021-2023) at 4 US institutions using axiUm (Henry Schein Corp) or Epic (Epic Systems) electronic health records. The authors transformed 2 annual measures involving caries risk assessment and risk-based preventive treatment into visit-level metrics using a 2 × 2 matrix framework: action due and performed, due and not …

Medical Aid In Dying: A Narrative Review Of The Recent Academic Literature In The United States., Holland Kaplan, Soraira Pacheco, Keziah M Thomas, Christopher L Ulmschneider, Anjiya Sulaiman, Chandni Lotwala, Derek Dawes, Issa A Hanna, Courtney Nguyen, Caroline G Snider, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Medical aid in dying (MAiD) is a practice in which a healthcare professional provides assistance to a terminally ill patient seeking to end their life. To assess how academic discourse may shape public opinion and policy in the United States, we conducted a narrative review of the literature published between 2020 and 2024. Articles were categorized as supportive, opposing, or neutral, and patterns were examined across authorship, disciplinary focus, and target populations. Our findings reveal that most recent publications adopt supportive or neutral stances toward MAiD, with a slight increase in opposition beginning in 2022. Authorship discipline strongly influenced position, …

Therapeutic Potential Of C1-Inhibitor In Vascular Diseases And Beyond, Linda Sundler Björkman, Harish Eswaran, Steven P Grover

Faculty, Staff and Student Publications

C1INH (C1-inhibitor) is a multifunctional SERPIN (serine protease inhibitor) that functions as a major negative regulator of the complement, coagulation, and kallikrein-kinin systems. C1INH products were originally developed for the treatment of hereditary angioedema associated with C1INH deficiency. A growing body of literature indicates that C1INH products may find utility in the management of several other disease states. In this review, we detail the key biological activities of C1INH and consider the pathophysiological role of C1INH targets in many conditions. The therapeutic potential of exogenous C1INH is highlighted in the settings of thromboembolism, ischemia-reperfusion injury, sepsis, transplantation, and coronavirus disease …

Urinary Biomarkers Of Acute Kidney Injury In Neonates < 25 Weeks’ Gestation: A Pilot Study, Jazmin D Humphreys, Aman Jain, Amir M Khan, Tina O Findley, Mar Romero-Lopez, Sepideh Saroukhani, Rita D Swinford, Matthew A Rysavy

Faculty, Staff and Student Publications

Background: Acute kidney injury (AKI) occurs in 30% of premature neonates and is associated with adverse outcomes that may be mitigated with early detection. Diagnosis of AKI relies on serum creatinine (SCr) which has several limitations, including lack of sensitivity and specificity. There are limited data on the utility of alternative urine biomarkers to predict AKI in neonates born at < 25 weeks' gestation.

Methods: Urine was collected from neonates born at < 25 weeks' gestation during the first postnatal week. Two urine AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and epidermal growth factor (EGF) were measured. Study participants were prospectively followed to determine development of AKI, defined by the neonatal modified Kidney Disease-Improving Global Outcomes (KDIGO) criteria, during the first postnatal week. The association of NGAL and EGF with AKI was analyzed using mixed-effect linear regression models adjusting for gestational age at birth.

Results: A total of 26 neonates were enrolled in this study. After adjusting for gestational age at birth, the mean difference in log-transformed biomarkers at three time points for urine NGAL and …

Markvcid2 Consortium For Clinical Validation Of Biomarkers Of Cerebral Small Vessel Disease: Validation Framework And Baseline Characteristics, Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau

Faculty, Staff and Student Publications

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by …

Outcomes Of Witnessed Versus Unwitnessed Patients With Stroke After Endovascular Therapy In The Extended Time Window, Liisa Tomppo, Nicolas Martinez-Majander, Muhammad M Qureshi, Thanh N Nguyen, Raul G Nogueira, Simon Nagel, Jelle Demeestere, Volker Puetz, Hilde Henon, Marta Olive-Gadea, João Pedro Marto, Anne Dusart, Peter A Ringleb, Osama O Zaidat, Diogo C Haussen, Mahmoud H Mohammaden, Mohamad Abdalkader, Jean Raymond, Santiago Ortega-Gutierrez, Sunil A Sheth, Hiroshi Yamagami, João Nuno Ramos, Francois Caparros, Daniel P O Kaiser, Marc Ribo, Sergio Salazar-Marioni, Kanta Tanaka, Pekka Virtanen, Ajit S Puri, James E Siegler, Syed F Zaidi, Mouhammad Jumaa, Eugene Lin, Jordi Mayol, Rita Ventura, Simon Winzer, Piers Klein, Flavio Bellante, Jorge Cespedes, Anke Wouters, Hesham E Masoud, Liqi Shu, Alicia C Castonguay, Christian Herweh, Monica Cheng, Wei Hu, Daniel Roy, Shadi Yaghi, Robin Lemmens, Charlotte Cordonnier, Markus A Möhlenbruch, Daniel Strbian

Faculty, Staff and Student Publications

Background: It remains unclear whether outcomes of patients treated with endovascular thrombectomy with large-vessel occlusion and unwitnessed onset of stroke differ from those with witnessed onset in the extended time window.

Methods: We enrolled patients with anterior circulation large-vessel occlusion (internal carotid artery, M1, or M2 segment of the middle cerebral artery) undergoing endovascular thrombectomy within 6 to 24 hours from the time last seen well, from 2014 to 2022, at 66 sites in Europe, North America, and Asia. Patients with a prestroke modified Rankin Scale score of >3 or age < 18 were excluded. We categorized patients by onset mode as witnessed or unwitnessed. The primary outcome was the modified Rankin Scale shift at 90 days. Secondary outcomes were functional independence, a composite of functional independence or return of Rankin to prestroke level, symptomatic intracranial hemorrhage, mortality, and a composite of severe disability or mortality at 90 days. We applied inverse probability of treatment weighting to compare outcomes between the groups.

Results: Of 5098 patients assessed for eligibility, we included …

Uterine Tachysystole And Associated Outcomes: A Systematic Review And Meta-Analysis, Fabrizio Zullo, Benedetta Licitra, Nandini Raghuraman, Alison G Cahill, Aaron W Roberts, Stephanie Roth, Daniele Di Mascio, Antonella Giancotti, Giuseppe Rizzo, Kristen A Cagino, Hector Mendez-Figueroa, Anthony C Sciscione, Suneet P Chauhan

Faculty, Staff and Student Publications

Objective: To determine whether uterine tachysystole is associated with adverse neonatal and maternal outcomes.

Data sources: A search strategy for PubMed (National Library of Medicine) was created, and the medical librarian translated the search for every database. The search strategy was peer reviewed by another medical librarian following the Peer Review of Electronic Search Strategies checklist. The databases included in this search were PubMed, Embase.com, Cochrane CENTRAL, CINAHL Ultimate, and Scopus; a combination of key words and subject headings was used.

Methods of study selection: Trials of nulliparous or multiparous parturients exposed to uterine tachysystole were included. Included studies compared …

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 …

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 …

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.

Sleep-Disordered Breathing In Newborns After Myelomeningocele Repair, Renée A Shellhaas, Fauziya Hassan, Thornton A Mason, Jagruti Anadkat, Ellen Bendel-Stenzel, Stephanie Eyerly-Webb, Cindy K Jon, Robin M Lloyd, Julie S Moldenhauer, Ramesha Papanna, John E Pascoe, Stefanie Riddle, Regina Reynolds, Brandon G Rocque, Narong Simakajornboon, Marjorie C Treadwell, R Bradley Troxler, Lydia S Youmans, Niko A Kaciroti, Harlan Mccaffery, Hemant A Parmar, Lora Merley, Stephanie Md Rau, Ronald D Chervin, John D E Barks

Faculty, Staff and Student Publications

Background & objective: Sleep-disordered breathing (SDB) may be a remediable contributor to abnormal cognitive outcomes for children with myelomeningocele. We investigated the frequency of SDB among neonates with fetal vs postnatal myelomeningocele repair.

Methods: In this nine-center, prospective, observational study, neonates with myelomeningocele born at more than 30 weeks gestational age underwent a 10-hour bedside polysomnogram at at least 35 weeks postmenstrual age, before hospital discharge. The primary outcome was SDB severity, reflected by the apnea-hypopnea index (AHI; number of respiratory events per hour of sleep). Decisions regarding surgical timing (fetal vs postnatal), technique (open fetal vs fetoscopic approach), and …

Association Of Intended Mode Of Delivery With Neonatal And Maternal Outcomes At 22-25 Weeks Of Gestation, Jameaka L Hamilton, Paula L Mcgee, Baha M Sibai, Michael W Varner, Alan T N Tita, Monica Longo, Edward F Bell, Barbara J Stoll, John M Thorp, Uma M Reddy, Heather A Frey, Emily S Miller, Dwight J Rouse, Hyagriv N Simhan, Jennifer L Bailit, Lorraine Dugoff, George R Saade

Faculty, Staff and Student Publications

Objective: To compare the risk of neonatal and maternal morbidity and mortality among individuals who delivered between 22 and 25 weeks of gestation by intended mode of delivery.

Methods: This was a secondary analysis of an observational cohort including participants with a singleton pregnancy delivered by planned cesarean delivery or after a trial of labor from 22 0/7 to 25 6/7 weeks of gestation. This analysis was limited to those who received both antenatal steroids and neonatal resuscitation. The primary outcome was a composite of neonatal death or severe neonatal morbidity. Secondary outcomes included neonatal mortality and measures of neonatal …