Genetic Phenomena Commons^™

Non-Invasive Measurement Of Elasticity In Glioblastoma Multiforme Validates Decreased Tmz Sensitivity In Astrocyte Co-Culture, Megan Mendieta, Maryam Hatami, Manmohan Singh, Sajedeh Saeidi Fard, Mohammad Dehshiri, Alexander Schill, Dmitry Nevozhay, Salavat Aglyamov, Bulent Ozpolat, Konstantin V Sokolov, Yasemin M Akay, Kirill V Larin, Metin Akay

Faculty, Staff and Student Publications

Goal: In this research, we investigated the changes in elasticity of in vitro glioblastoma multiforme (GBM) spheroids when treated with the gold standard chemotherapy for GBM, Temozolomide (TMZ). Additionally, we aimed to use this alternative biomarker to assess how modifying the tumor microenvironment (TME) with the addition of human astrocytes (HA) would influence treatment efficacy. Methods: Spheroid stiffness was investigated using advanced non-invasive optical techniques, nanobomb optical coherence elastography (nb-OCE) and Brillouin microscopy to obtain new biomechanical insights by assessing local tumor progression or response to therapy using GBM cells (LN229). Results: The treated monocultured GBM groups showed a significant …

Examining The Presence And Effects Of Coherence And Fragmentation In The Gulf Of Maine Fishery Management Network, Derek Katznelson, Antonia Sohns, Dongkyu Kim, Evelyn Roozee, William R Donner, Andrew M Song, Jasper R De Vries, Owen Temby, Gordon M Hickey

Faculty, Staff and Student Publications

Natural resource management networks cohere due to mutual dependencies and fragment, in part, due to the perceived risks of interaction. However, research on these networks has tended to accept coherence a priori rather than problematizing dependence, and few studies exist on interorganizational risk perception. This article presents the results of a study operationalizing these concepts and measuring the distribution of three types of dependence (capital, legitimacy, and regulatory) and two types of perceived risk (performance and sanction) among nearly fifty stakeholder groups and organizations participating in the management of fisheries in the binational Gulf of Maine. The analysis reveals an …

Nrg Oncology White Paper On The Relative Biological Effectiveness In Proton Therapy, Harald Paganetti, Charles B Simone, Walter R Bosch, Daphne Haas-Kogan, David G Kirsch, Heng Li, Xiaoying Liang, Wei Liu, Anita Mahajan, Michael D Story, Paige A Taylor, Henning Willers, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of …

Editorial: Ovarian Cancer Targeted Medication: Parp Inhibitors, Anti-Angiogenic Drugs, Immunotherapy, And More, Volume Ii, Zhi-Bin Wang, De-Hua Liao, Guang Lei, Zhao-Qian Liu, Nayiyuan Wu, Jing Wang

Faculty, Staff and Student Publications

No abstract provided.

Individualized Frequency And Montage Tacs To Engage Theta-Gamma Coupling And Enhance Working Memory In Mild Cognitive Impairment, Mina Mirjalili, Iryna S Palamarchuk, Heather Brooks, Reza Zomorrodi, Ashley Melichercik, Wei Wang, Sean M Nestor, Daniel M Blumberger, Abhishek Datta, Christopher Bowie, Bernadette Mdawar, Kullervo Hynynen, Sanjeev Kumar, Tarek K Rajji

Faculty, Staff and Student Publications

Mild Cognitive Impairment (MCI) is a clinical prodromal stage of Alzheimer's disease. Enhancing executive functions in patients with MCI could optimize cognitive compensatory mechanisms and slow cognitive decline. The prefrontal cortex (PFC) and its connections to the hippocampus support executive functions, including working memory. Transcranial alternating current stimulation (tACS) can modulate these connections by engaging theta-gamma coupling (TGC) and may thereby strengthen working memory. This study, "tACS to engage theta-gamma coupling and enhance working memory in MCI" (tACS-MCI), will assess the feasibility and cognitive effects of EEG and MRI-guided individualized tACS. The stimulation will target the prefrontal and temporal cortices …

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

Faculty, Staff and Student Publications

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 …