Genetic Phenomena Commons^™

Comprehensive Genomic Analysis Reveals Molecular Heterogeneity In Pediatric Alk-Positive Anaplastic Large Cell Lymphoma, Timothy I Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S Lim, Vasiliki Leventaki

Faculty, Staff and Student Publications

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription …

Global Research Trends And Focus On Immunotherapy For Endometrial Cancer: A Comprehensive Bibliometric Insight And Visualization Analysis (2012–2024), Yachen Xu, Tao Wang, Xiaojing Liang, Jie Yang, Yuxiang Zhang, Shan Bao

Faculty, Staff and Student Publications

Background: This study conducted a novel systematic bibliometric and visualization analysis of global literature on immunotherapy for endometrial cancer (EC) to explore dynamic trends, research hotspots, and emerging topics, providing valuable references for future research.

Methods: Articles and reviews on EC immunotherapy published between 2012 and August 2024 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric tools, CiteSpace and VOSviewer, were used to analyze clustering patterns and research dynamics.

Results: A total of 861 articles were contributed by 5,331 authors from 1,392 institutions across 58 countries or regions, involving 1,823 keywords. China demonstrated outstanding performance in this …

Long-Term Symptom Burden In A Young, Ambulatory Cohort After The Omicron Outbreak In China, Simeng Ren, Yumeng Tan, Hongkun Xu, Mian Wang, Rumei Xiang, Jiayue Jin, Baojin Han, Jiaheng Shi, Jingyu Zhang, Jinliang Yang, Xin Tian, Ying Li, Jiaojiao Chen, Wenzheng Zhang, Jingqi Yang, Xin Shelley Wang, Qiuling Shi, Jie Liu

Faculty, Staff and Student Publications

Introduction: At the end of 2022, an outbreak of the Omicron BF.7 and BA.5.2 subvariants of SARS-CoV-2 occurred in China. In this prospective cohort study, we investigated the pattern of development of major symptom burden and influencing factors in infected Chinese patients.

Methods: First-time infected outpatients were enrolled from December 7, 2022, to January 11, 2023 (N = 355). The prevalence of symptoms was monitored by a repeated patient-reported quantitative symptom survey over nine months.

Results: At the onset of the infection, the most prevalent symptoms (score ≥1 on a 0-10 numeric rating scale) were fatigue (91.8%), cough (91.8%), …

Characterization Of Additive Gene-Environment Interactions For Colorectal Cancer Risk, Claire E Thomas, Yi Lin, Michelle Kim, Eric S Kawaguchi, Conghui Qu, Caroline Y Um, Brigid M Lynch, Bethany Van Guelpen, Kostas Tsilidis, Robert Carreras-Torres, Franzel J B Van Duijnhoven, Lori C Sakoda, Peter T Campbell, Yu Tian, Jenny Chang-Claude, Stéphane Bézieau, Arif Budiarto, Julie R Palmer, Polly A Newcomb, Graham Casey, Loic Le Marchandz, Marios Giannakis, Christopher I Li, Andrea Gsur, Christina Newton, Mireia Obón-Santacana, Victor Moreno, Pavel Vodicka, Hermann Brenner, Michael Hoffmeister, Andrew J Pellatt, Robert E Schoen, Niki Dimou, Neil Murphy, Marc J Gunter, Sergi Castellví-Bel, Jane C Figueiredo, Andrew T Chan, Mingyang Song, Li Li, D Timothy Bishop, Stephen B Gruber, James W Baurley, Stephanie A Bien, David V Conti, Jeroen R Huyghe, Anshul Kundaje, Yu-Ru Su, Jun Wang, Temitope O Keku, Michael O Woods, Sonja I Berndt, Stephen J Chanock, Catherine M Tangen, Alicja Wolk, Andrea Burnett-Hartman, Anna H Wu, Emily White, Matthew A Devall, Virginia Díez-Obrero, David A Drew, Edward Giovannucci, Akihisa Hidaka, Andre E Kim, Juan Pablo Lewinger, John Morrison, Jennifer Ose, Nikos Papadimitriou, Bens Pardamean, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Xuechen Chen, Duncan C Thomas, Elizabeth A Platz, W James Gauderman, Ulrike Peters, Li Hsu

Faculty, Staff and Student Publications

Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

Results: There was no evidence of multiplicative interaction …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin

Correction: Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

[This corrects the article DOI: 10.3389/fnhum.2025.1629499.].

Mechanisms Of How Sarcopenia Affects Functional Outcomes In Acute Ischaemic Stroke, Dong-Seok Gwak, Jinyong Chung, Dawid Schellingerhout, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Dong-Eog Kim

Faculty, Staff and Student Publications

Sarcopenia, a common geriatric condition characterized by the loss of skeletal muscle mass and function, can negatively affect functional outcomes in acute ischaemic stroke; however, the underlying mechanisms remain unclear. We hypothesized that sarcopenia affects post-stroke outcomes, mediated through its impact on dysphagia, early neurological deterioration, or post-stroke recovery, particularly in patients with motor deficits. To explore this hypothesis, we included 600 consecutive elderly (≥65 years) patients with acute (< 1 week) ischaemic stroke and assessed: (i) the relationships sarcopenia has with dysphagia, early neurological deterioration and various phases of recovery after stroke (in-hospital, post-discharge [up to 3 months], and chronic [3 months to 1 year]) and (ii) whether either presenting symptoms or lesion locations modify the impact of sarcopenia on stroke outcomes. Temporal muscle thickness, a marker of sarcopenia, was measured by brain magnetic resonance imaging and dichotomized into low versus high temporal muscle thickness at the 25th percentile cut-off point. Logistic regression analysis, mediation analysis and statistical brain mapping were conducted. Mean age was 75.3 ± 6.1 years and 303 (50.5%) were male. Low temporal muscle thickness (< 5.1 mm) was independently associated with dysphagia (adjusted odds ratio 1.89 [95% confidence interval 1.06–3.37], P = 0.03), early neurological deterioration (adjusted odds ratio 2.75 [95% confidence interval 1.61–4.71], P < 0.001) and post-discharge recovery (adjusted odds ratio 0.56 [95% confidence interval 0.34–0.94], P = 0.03) but not with in-hospital or chronic recovery. In addition, dysphagia, early neurological …

Recovery Of Verbal Working Memory Depends On Left Hemisphere White Matter Tracts, Randi C Martin, Junhua Ding, Ali I Alwani, Steve H Fung, Tatiana T Schnur

Faculty, Staff and Student Publications

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere. Many investigations of recovery focus on changes in gray matter regions, whereas relatively few examine white matter tracts and none address the role of these tracts in the recovery of verbal working memory. The present study addressed these gaps, examining the role of left versus right hemisphere tracts in the longitudinal recovery of phonological and semantic working memory. For 24 individuals with left hemisphere stroke, we assessed working memory performance within 1 …

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nisha Rathi, Nicole Hensch, Vera De La Cruz, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

Ai/Ml-Empowered Approaches For Predicting T Cell-Mediated Immunity And Beyond, Cheng-Chi Chao, Yulun Chiu, Lucas Yeung, Cassian Yee, Chongming Jiang, Xiling Shen

Faculty, Staff and Student Publications

T cells play a dual role in various physiopathological states, capable of eliminating tumors and infected cells, while also playing a pathogenic role when activated by autoantigens, causing self-tissue damage. The regulation of T cell-peptide/major histocompatibility complex (TCR-pMHC) recognition is crucial for maintaining disease balance and treating cancer, infections, and autoimmune diseases. Despite efforts, predictive models of TCR-pMHC specificity are still in the early stages. Inspired by advances in protein structure prediction via deep neural networks, we evaluated AlphaFold 3 (AF3)-based AI computation as a method to predict TCR epitope specificity. We demonstrate that AlphaFold can model TCR-pMHC interactions, distinguishing …

Innovative Approaches In Precision Radiation Oncology: Advanced Imaging Technologies And Challenges Which Shape The Future Of Radiation Therapy, Yue Yan, Daniel A Alexander, Bryan P Bednarz, Lawrence F Bronk, Huixiao Chen, David J Gladstone, Bin Han, Christopher M Iannuzzi, Yuting Li, Ngoc Nguyen, Natasha Mulenga, Natalie N Viscariello, Yuenan Wang, Joseph Weygand, Yana Zlateva, Fada Guan

Faculty, Staff and Student Publications

Radiation oncology is undergoing a transformative shift toward precision medicine through unprecedented advances in imaging technologies that enable increasingly personalized and adaptive cancer treatment. This comprehensive review synthesizes the underlying physical principles, current clinical applications, technical challenges, and quality assurance requirements across the complete spectrum of emerging imaging-guided radiation therapy approaches. We examine magnetic resonance-guided radiotherapy systems that enable daily soft-tissue visualization and online plan adaptation, positron emission tomography-guided platforms that allow real-time tracking of metabolically active tumor regions, advanced cone beam computed tomography systems supporting rapid adaptive workflows through artificial intelligence-enhanced image generation, and novel applications including Cherenkov radiation …

Correction: Innovative Approaches In Precision Radiation Oncology: Advanced Imaging Technologies And Challenges Which Shape The Future Of Radiation Therapy, Yue Yan, Daniel A Alexander, Bryan P Bednarz, Lawrence F Bronk, Huixiao Chen, David J Gladstone, Bin Han, Christopher M Iannuzzi, Yuting Li, Ngoc Nguyen, Natasha Mulenga, Natalie N Viscariello, Yuenan Wang, Joseph Weygand, Yana Zlateva, Fada Guan

Faculty, Staff and Student Publications

No abstract provided.

Refining Breast Cancer Genetic Risk And Biology Through Multi-Ancestry Fine-Mapping Analyses Of 192 Risk Regions, Guochong Jia, Zhishan Chen, Jie Ping, Qiuyin Cai, Ran Tao, Chao Li, Joshua A Bauer, Yuhan Xie, Stefan Ambs, Mollie E Barnard, Yu Chen, Ji-Yeob Choi, Yu-Tang Gao, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Motoki Iwasaki, Esther M John, Sun-Seog Kweon, Christopher I Li, Koichi Matsuda, Keitaro Matsuo, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Sue K Park, Boyoung Park, Michael F Press, Maureen Sanderson, Dale P Sandler, Chen-Yang Shen, Melissa A Troester, Song Yao, Ying Zheng, Thomas Ahearn, Abenaa M Brewster, Adeyinka Falusi, Anselm J M Hennis, Hidemi Ito, Michiaki Kubo, Eun-Sook Lee, Timothy Makumbi, Paul Ndom, Dong-Young Noh, Katie M O'Brien, Oladosu Ojengbede, Andrew F Olshan, Min-Ho Park, Sonya Reid, Taiki Yamaji, Gary Zirpoli, Ebonee N Butler, Maosheng Huang, Siew-Kee Low, John Obafunwa, Clarice R Weinberg, Haoyu Zhang, Hongyu Zhao, Michelle L Cote, Christine B Ambrosone, Dezheng Huo, Bingshan Li, Daehee Kang, Julie R Palmer, Xiao-Ou Shu, Christopher A Haiman, Xingyi Guo, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 …

Rationale And Design For A Phase Iiib Trial Of First-Line Tremelimumab Plus Durvalumab Versus Pembrolizumab, In Combination With Chemotherapy, In Patients With Non-Squamous Metastatic Non-Small-Cell Lung Cancer And Mutations Or Co-Mutations In Stk11, Keap1, Or Kras: The Triton Study, Ferdinandos Skoulidis, Hossein Borghaei, Edward B Garon, Ticiana A Leal, Jacob Kaufman, Stephen V Liu, Eric Nadler, Sandip Pravin Patel, Solange Peters, Biagio Ricciuti, Ashish Gautam, Ugochinyere Emeribe, Luisa Luciani-Silverman, John V Heymach

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Background: Metastatic non-small-cell lung cancers (mNSCLC) harboring mutations in STK11 or KEAP1 are associated with an immunosuppressive tumor microenvironment and reduced responsiveness to PD-(L)1 inhibitor-based therapy, which is particularly notable when these genes are co-mutated with each other or with KRAS. Patients with these mNSCLC subtypes may benefit from combinations including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, aimed at enhancing immune responses.

Objectives: TRITON is an ongoing study comparing tremelimumab plus durvalumab and chemotherapy with pembrolizumab plus chemotherapy as first-line treatment for patients with non-squamous mNSCLC and mutations or co-mutations in STK11, KEAP1, or KRAS.

Design: Phase …

Improved Survival And Decreased Cancer Deaths In Young Adults With Cancer After Passage Of The Affordable Care Act Dependent Coverage Expansion, Michael Roth, Clark R Andersen, Amy Berkman, Stuart Siegel, Branko Cuglievan, J Andrew Livingston, Michelle Hildebrandt, Jaime Estrada, Archie Bleyer

Faculty, Staff and Student Publications

Background: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited?

Methods: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative …

Detrimental Effects Of Space Flight On The Lumbar Spine May Be Correlated To Baseline Degeneration: Insights From An Advanced Mr Imaging Study, Rakan Bokhari, Daniel G Bisson, Maryse Fortin, Marie Vigouroux, Juan Pablo Cata, Ken-Pin Hwang, Melissa M Chen, Guillermo Ceniza-Bordallo, Jean A Ouellet, Pablo M Ingelmo

Faculty, Staff and Student Publications

Introduction: Pain in lower back is a common condition reported by astronauts, both during and after space missions. Investigating the alterations in the spine and the mechanisms driving these changes is essential for a deeper understanding of how microgravity impacts the human spine. This knowledge could also open pathways for therapeutic or preventive interventions. Nevertheless, there is a limited evidence regarding changes in intervertebral discs (IVDs) due to space travel.

Materials and methods: In this study, 2 astronauts were enrolled in a space travel. Before the space flight, a lower back magnetic resonance imaging (MRI) scan was performed. We repeated …

Utility Of Pre-Procedural [99mtc]Tcmaa Spect/Ct Multicompartment Dosimetry For Treatment Planning Of 90y Glass Microspheres In Patients With Hepatocellular Carcinoma: Comparison Of Anatomic Versus [99mtc]Tcmaa-Based Segmentation, Marnix Lam, Etienne Garin, Paul Haste, Alban Denys, Brian Geller, S Cheenu Kappadath, Cuneyt Turkmen, Daniel Y Sze, Hamad Saleh Alsuhaibani, Ken Herrmann, Marco Maccauro, Murat Cantasdemir, Matthew Dreher, Kirk D Fowers, Vanessa Gates, Riad Salem

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Purpose: Pre-treatment [99mTc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments.

Materials and methods: Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]TcMAA SPECT/CT. Logistic regression and …

Fatty Pancreas On Eus: Risk Factors, Correlation With Ct/Mri, And Implications For Pancreatic Cancer Screening, Ramez M Ibrahim, Shantanu Solanki, Wei Qiao, Hyunsoo Hwang, Ben S Singh, Irina M Cazacu, Adrian Saftoiu, Matthew H G Katz, Michael P Kim, Florencia Mcallister, Manoop S Bhutani

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Background and objectives: Fatty pancreas (FP), traditionally perceived as a benign finding, has been undergoing scrutiny lately due to growing evidence linking it to various disease states, including increased risk for pancreatic cancer (PC).

Methods: A retrospective study of patients who underwent EUS at a single institution from August 2007 to October 2023, conducted by one endosonographer with more than 25 years of experience. Focusing on individuals identified with FP during EUS, we compared these findings with corresponding findings on computed tomography/magnetic resonance imaging (CT/MRI) conducted within 3 months or 1 year prior to or following EUS.

Results: Ninety-one patients …

Sex And Apoe Ε4 Allele Differences In Longitudinal White Matter Microstructure In Multiple Cohorts Of Aging And Alzheimer's Disease, Amalia Peterson, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Kacie D Deters, Niranjana Shashikumar, Kimberly R Pechman, Michael E Kim, Chenyu Gao, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Katherine A Gifford, Jo Ellen Wilson, Francis E Cambronero, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Mohamad Habes, Di Wang, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

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Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status.

Results: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.

Discussion: …

Consensus Guidelines For Delineation Of Clinical Target Volumes For Intensity Modulated Radiation Therapy For Intact Cervical Cancer: An Update, Emma C Fields, Walter R Bosch, Kevin V Albuquerque, Rohini Bhatia, Junzo Chino, Brandon Dyer, Beth Erickson, Denise Fabian, David Gaffney, Scott Glaser, Kathy Han, Lara Hathout, I-Chow Hsu, Naresh Jegadeesh, Jenna Kahn, Elizabeth Kidd, Ann Klopp, Eric Leung, Lilie Lin, Michelle Ludwig, Tianjun Ma, Loren Mell, Jyoti Mayadev, Ivy Petersen, Lorraine Portelance, Dominique Rash, Neil Taunk, Akila Viswanathan, Aaron Wolfson, Catheryn Yashar, Anamaria Yeung, Emi Yoshida, Christine M Fisher

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Purpose: Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques.

Methods and materials: Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) …

Modest Radiation Dose Escalation For Early-Stage Anal Cancer: Cancer Control And Toxicity Outcomes, Sage Copling, Michael K Rooney, Prajnan Das, Eugene J Koay, Ethan B Ludmir, Bruce D Minsky, Sonal S Noticewala, Grace L Smith, Emma B Holliday

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Background: The optimal dose for patients with early-stage squamous cell carcinoma of the anus (SCCA) is unknown. We aimed to evaluate the impact of modest dose escalation (54 Gray (Gy)) compared with standard dose (50 Gray) on the disease-free survival and toxicity outcomes for patients with T1-2N0 SCCA.

Methods: Patients with T1-T2N0 SCCA treated with definitive radiation from 1/1/2003 until 6/31/2022 were included in this retrospective analysis. Regression discontinuity analysis was performed to evaluate for a potential causal effect of modest dose escalation on freedom from local recurrence (FFLR). Cox proportional hazards model was generated to estimate the effect of …

The Primary Cilia: Orchestrating Cranial Neural Crest Cell Development, Hiroyuki Yamaguchi, Matthew D Meyer, William B Barrell, Maryam Faisal, Rebecca Berdeaux, Karen J Liu, Yoshihiro Komatsu

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Primary cilia (hereafter "cilia") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies. However, the detailed pathological mechanisms of craniofacial ciliopathies remain unclear. This perspective discusses our current understanding of the role of cilia in cranial neural crest cells. We also describe potential mechanisms of ciliogenesis in cranial neural crest cells, which may contribute to unraveling the complex pathogenesis of craniofacial ciliopathies.

Inducing Hypertension In Myh11r247c/R247c Mice Triggers Aortic Dissections With Increased Focal Adhesion Kinase Signaling, Callie S Kwartler, Shanzhi Wang, Zhen Zhou, Pujun Guan, Yang Yu, Xue-Yan Duan, Theodore Zhang, Jiyuan Chen, Elaine C Davis, Dianna M Milewicz

Faculty, Staff and Student Publications

Objective: We sought to determine if hypertension in combination with a "variant of uncertain significance" that disrupts protein function, MYH11 p.Arg247Cys, would induce aortic dissections in a mouse model.

Approach and results: Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and Myh11R247C/R247C mice and triggered type A dissections with cardiac tamponade in 20% of the Myh11R247C/R247C mice. Myh11R247C/R247C aortas have aberrant smooth muscle contractile unit-elastin connections by transmission electron microscopy, along with increased focal adhesion signaling at baseline, which further increases with hypertension.

Conclusion: Gene-environment interactions trigger aortic dissections in Myh11R247C/R247C mice.

Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Background: Posttraumatic stress disorder (PTSD) symptoms are common in people with cocaine use disorder (CUD), and even sub-threshold PSTD symptoms result in worse treatment outcomes. Difficulties with reward functioning may drive this comorbidity. Impairments in reward functioning are prominent in both PTSD and CUD and contribute to development of substance use problems after trauma. There are three distinct reward processes that may be involved in the PTSD/CUD overlap: consummatory reward (ability to experience pleasure), motivational reward (willingness to exert effort for rewards), and reward learning (adapting behavior based on reward history). Here we test whether impairments in these reward functions …

Hepatic Metabolic Signature And Its Association With The Response To Immunotherapy In Hepatocellular Carcinoma, Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee

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Introduction: Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.

Methods: Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to …

Immune Responses In Rodent Whole Eye Transplantation: Elucidation And Preliminary Investigations Into Rejection Diagnosis And Monitoring, Bing Li, Yong Wang, Charles R Owens, Touka Banaee, Charleen T Chu, Kayvon Jabbari, Anna D Lee, Neil J Khatter, Alan G Palestine, An-Jey A Su, Christene A Huang, Kia M Washington

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Background: Whole Eye Transplantation (WET) offers potential for vision restoration but is hindered by the complex challenge of immune rejection. Understanding and closely monitoring these immunological responses is crucial for advancing WET. This study delves into the timeline and nature of immune responses in a rodent model of WET without immunosuppression, aiming to elucidate a detailed picture of the immune landscape post-transplantation and establish innovative diagnostic and monitoring methods.

Methods: We employed a multi-faceted approach to analyze immune responses post-WET, including assessments of gross changes in corneal transparency, thickness, and skin condition. Histopathological examinations of both ocular and surrounding skin …

Clinical Criteria For Limbic-Predominant Age-Related Tdp-43 Encephalopathy, David A Wolk, Peter T Nelson, Liana Apostolova, Konstantinos Arfanakis, Patricia A Boyle, Cynthia M Carlsson, Nick Corriveau-Lecavalier, Penny Dacks, Bradford C Dickerson, Kimiko Domoto-Reilly, Brittany N Dugger, Rebecca Edelmayer, David W Fardo, Michel J Grothe, Timothy J Hohman, David J Irwin, Gregory A Jicha, David T Jones, Claudia H Kawas, Edward B Lee, Karen Lincoln, Gladys E Maestre, Elizabeth C Mormino, Chiadi U Onyike, Ronald C Petersen, Gil D Rabinovici, Rosa Rademakers, Rema Raman, Katya Rascovsky, Robert A Rissman, Emily Rogalski, Philip Scheltens, Reisa A Sperling, Hyun-Sik Yang, Lei Yu, Henrik Zetterberg, Julie A Schneider

Faculty, Staff and Student Publications

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of …

A Biomechanical Study Of Neck Strength And Impact Dynamics On Head And Neck Injury Parameters, Rahid Zaman, Mohammad Ibrahim Hossain, Ahmed Zubayer Raiyan, Shuvo Chowdhury, Aaron Jackson, Arthur Thomas Koster, Ashfaq Adnan

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Introduction: Head and neck injuries, including traumatic brain injuries (TBI), are a leading cause of disability and death worldwide. It affects millions of people worldwide, from automobiles to sports to military personnel. This study investigates the influence of impact locations, severities, and neck strength on head and neck injury parameters using a musculoskeletal head-neck model in OpenSim software.

Methods: We hypothesize that eccentric impacts, particularly those on the anterolateral side, increase GAMBIT and Neck Injury Criteria (NIC) due to elevated rotational accelerations, and that higher neck strength mitigates GAMBIT and NIC under these impacts. To test our hypotheses, we investigated …

A Network-Based Discovery Of Prognostic Markers In Recurrent Idh Wild-Type Gliomas, Yang Liu, Jason Huse, Kasthuri Kannan

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Background: Isocitrate dehydrogenase wild-type (IDH wild-type) gliomas represents the most aggressive subtype of diffuse gliomas, characterized by therapeutic resistance and dismal prognosis. Despite advances in molecular classification, reliable prognostic biomarkers for these tumors remain limited, particularly for recurrent disease. This study aims to identify gene expression signatures associated with survival outcomes in recurrent IDH wild-type gliomas, with the goal of improving patient stratification and potential therapeutic targeting.

Methods: We analyzed gene expression data from 180 recurrent IDH wild-type glioma samples from the Glioma Longitudinal AnalySiS (GLASS) Consortium. Using multiple computational approaches including a novel network-based method (netSurvival) and various survival …

Exposure Therapy Consortium: Outcomes Of The Proof-Of-Principle Study, Jasper A J Smits, Jonathan S Abramowitz, Rebecca A Anderson, Joanna J Arch, Daniel Badeja, Snir Barzilay, Amanda N Belanger, Thomas Borchert, Emma Bryant, Alane S Burger, Laura J Dixon, Christina D Dutcher, Hayley E Fitzgerald, Bronwyn M Graham, Anke Haberkamp, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, David Johnson, Baraa Q Kabha, Alex Kirk, Jürgen Margraf, Peter M Mcevoy, Bryan Mcspadden, Jill Newby, Michael W Otto, Santiago Papini, E Marie Parsons, Andre Pittig, Roxana Pittig, Winfried Rief, Svenja Schaumburg, Kiara R Timpano, Lena Waltemate, Andre Wannemüller, Cornelia Weise, Exposure Therapy Consortium

Faculty, Staff and Student Publications

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) …