Genetic Phenomena Commons^™

Representation Of Neuro-Oncology In American Neurology Departments: An Analysis Of Grand Rounds And Perspectives From Faculty And Residents, Elizabeth C Neil, Aubree Bruhnding, Zubair A Ahmed, Priya U Kumthekar, Nicholas A Blondin, Chirag B Patel, Feng Wang, Hongyu Miao, Noah L Rosen, Rashmi B Halker Singh, Mark J Burish, Zachary A Corbin

Faculty, Staff and Student Publications

Background: Neuro-oncology education in American neurology departments is highly variable, with no clear guidelines on appropriate practices. To better understand its current state, we focus on the perspective of departmental Grand Rounds (GR), views of adult neurology residency program directors (ANRPD), neuro-oncologists, and residents.

Methods: First, we obtained GR series from academic years 2017-2018 and 2018-2019 via an online search and direct emails to neurology residency programs. Second, two online surveys were dispensed to ANRPD and neuro-oncologists. Third, a cohort of neurology residents completed surveys with pre/post-didactic tests.

Results: Neuro-oncology consisted of 7% (28/ 411) GR in 2017-2018 and 6% …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Addressing Controversy In Fusobacterium Nomenclature: What Exactly Does “F Nucleatum” Refer To?, Martha A Zepeda-Rivera, Floyd E Dewhirst, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

The F. nucleatum group (sensu lato) is historically composed of four subspecies (F. nucleatum subsp. animalis, F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii). Although F. nucleatum sensu lato members are typically associated with oral disease, they have recently been shown to disseminate to the gastrointestinal tract and are associated with adverse health conditions such as inflammatory bowel disease and colorectal cancer (CRC). A growing debate over the nomenclature applied to Fusobacterium taxonomy has resulted in different names for these lineages, shifting them from their historic subspecies designations to …

Evaluation Of Renal Masses With Cest Mri: Protocol Optimization And Preliminary Results, Xiaojing Wang, Jochen Keupp, Ivan E Dimitrov, Ananth Madhuranthakam, Durga Udayakumar, Emin Albayrak, Payal Kapur, Robert E Lenkinski, Ivan Pedrosa, Elena Vinogradov

Faculty, Staff and Student Publications

Purpose: This study investigates the application of CEST MRI in human kidneys, with the overarching goal of developing CEST MRI for renal mass characterization. Here, the focus is on the development of a protocol and the proof-of-principle evaluation of CEST for the characterization of clear cell renal cell carcinoma (ccRCC).

Methods: Ten healthy volunteers and five patients diagnosed with ccRCC underwent CEST MRI scans at 3 T. The sequence performance was characterized in healthy volunteers and tested using three saturation power levels, B1rms = 0.7, 1.2, and 1.6 μT. We compared the magnetization transfer ratio asymmetry (MTRasym) values at 1.0, …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Kyungmin Kim, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Courtney Dinardo, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

Bayesian Integrated Learning Of Longitudinal Dose-Response Relationships Via Decentralized Clinical Trials, Jingyi Zhang, Tuo Wang, Yongming Qu, Fangrong Yan, Suyu Liu

Faculty, Staff and Student Publications

Decentralized clinical trials (DCTs) extend trial activities beyond traditional sites, enhancing access, convenience, efficiency, and result generalizability. They are particularly promising for chronic conditions like diabetes and obesity, which require longer study durations to evaluate drug effects. However, decentralized data collection raises concerns about increased variability and potential biases. This paper presents a novel Bayesian integrated learning procedure to analyze dose-response relationships using longitudinal data from a phase II DCT that combines centralized and decentralized data collection. We generalize a parametric exponential decay model to handle mixed data sources and apply Bayesian spike-and-slab priors to address biases and uncertainties from …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Malia Gasteier, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Tianyi Zhou, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Symptom Burden, Healthcare Utilization, And Risky Behaviors In Survivors Of The Childhood Cancer Survivor Study (Ccss): An Observation Cohort Study, Rachel Webster, Deo Kumar Srivastava, Lu Xie, Himani Darji, Wei Liu, Tara M Brinkman, Kirsten K Ness, Bernard Fuemmeler, Alicia S Kunin-Batson, I-Chan Huang, Gregory T Armstrong, Rebecca M Howell, Daniel M Green, Yutaka Yasui, Kevin R Krull

Faculty, Staff and Student Publications

Background: Childhood cancer survivors face physical, psychological, and neurological symptoms that contribute to risky health behaviors and increased healthcare utilization. Traditional survivorship care models overlook risk associated with this symptom burden. The current study examined symptoms phenotypes to identify high-risk groups.

Methods: Five-year survivors (N = 17,231; Mean [standard deviation] age = 27.4 [5.98]; 80% non-Hispanic White; 48% female) from the Childhood Cancer Survivor Study (NCT01120353) self-reported symptoms and risky behavior at baseline and first follow-up (original cohort data collection: baseline 1994-1998 and follow-up 2002-2004; expansion cohort: baseline 2008-2010 and follow-up 2014-2016). Medical records were extracted through chart …

Differential Effects Of Murine Stroke Models On Dopaminergic Neurons, Glial Responses, And Neurobehavioral Outcomes, Sidra Tabassum, Heng Hu, Silin Wu, Shuning Huang, Bosco Seong Kyu Yang, Aaron W Gusdon

Faculty, Staff and Student Publications

Stroke is a leading cause of disability worldwide, often resulting in persistent motor, cognitive, and emotional impairments. While the hippocampus and amygdala play critical roles in post-stroke behavioral changes, specific neuronal alterations and prolonged glial responses within these regions across different stroke types remain unclear. This study investigates the behavioral, neuronal, and glial effects of subarachnoid hemorrhage (SAH), transient middle cerebral artery occlusion (tMCAO), and photothrombotic stimulation (PTS) in mice. SAH and tMCAO models exhibited significant motor deficits, spatial and recognition memory impairments, and increased anxiety- and depressive-like behaviors, whereas the PTS model showed similar motor and cognitive impairments but …

Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, J Yuyang Lu, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. …

Experimental Design And Control Methods For Dose Rate Optimization In A Synchrotron-Based Proton Therapy Beamline, Jason Tang, Daniel Liu, Jacob Mathew, Sabrina Campelo, Lawrence Bronk, Yuting Li

Faculty, Staff and Student Publications

Background: Ultra-high dose rate radiotherapy (typically defined >40 Gy/s) has shown promise for enhanced normal tissue sparing while maintaining tumor control, termed the FLASH effect when this biological response is observed. However, precise dose rate control remains a technical challenge in proton therapy systems, particularly for research applications investigating dose rate effects.

Purpose: To develop and validate a passive beam modulation technique using tungsten scatterers for controllable dose rate adjustment in a synchrotron-based proton therapy beamline without modifying accelerator parameters.

Methods: We investigated dose rate modulation using tungsten foils of varying thicknesses (0.1-3.5 mm) positioned upstream in an 87.2 MeV …

Sahrang: Subarachnoid Hemorrhage Recovery And Galantamine: A Pilot Multicenter Randomized Placebo-Controlled Trial, Bosco Seong Kyu Yang, Jude P J Savarraj, Elena Moreno, Kevin E Immanuel, Georgene Hergenroeder, Jung Hwan Kim, Claudia Pedroza, James C Grotta, Andrew Barreto, H Alex Choi

Faculty, Staff and Student Publications

Background: Subarachnoid hemorrhage (SAH) causes life-long neurologic dysfunction. Peripheral inflammatory processes as a reaction to brain injury have been shown to worsen outcomes after SAH. Galantamine has been shown to reduce proinflammatory microglial activities and improve synaptic connections. We hypothesize that galantamine treatment after SAH mitigates inflammation-mediated neuronal injury and improve outcomes. We conducted a pilot clinical trial to examine the tolerability and safety of galantamine in patients with SAH.

Methods: This prospective, multicenter, double-masked, randomized, placebo-controlled study contiguously screened and enrolled adult patients presenting with aneurysmal SAH with a Fisher grade of 3 within 72 h of symptom onset. …

Cutting Edge Developments In Bone Oncology – Highlights From The Cancer And Bone Society 2024 Annual Meeting, Deanna N Edwards, Shreya Patel, Gabriel M Pagnotti

Faculty, Staff and Student Publications

The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society's enduring mission to advance understanding of cancer-bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year's meeting featured a comprehensive scientific program spanning tumor-bone biology, therapeutic innovation, and microenvironmental regulation. Clinical sessions emphasized the evolution of bone-targeted treatments such as bisphosphonates, denosumab, and …

Regional Brain Morphology And Current Antidepressant Use: Findings From 32 International Cohorts From The Enigma Major Depressive Disorder Working Group, Chaira Serrarens, Yara J Toenders, Elena Pozzi, André Aleman, Nina Alexander, Vladimir Belov, Katharina Brosch, Robin Bülow, Geraldo Filho Busatto, Liliana P Capitão, Colm G Connolly, Baptiste Couvy-Duchesne, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Greig I De Zubicaray, Danai Dima, Katharina Dohm, Verena Enneking, Tracy Erwin-Grabner, Ulrika Evermann, Cynthia H Y Fu, Paola Fuentes-Claramonte, Beata R Godlewska, Ali Saffet Gonul, Ian H Gotlib, Roberto Goya-Maldonado, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Oliver Gruber, Tim Hahn, Geoffrey Hall, Ben J Harrison, Walter Heindel, Marco Hermesdorf, Tiffany C Ho, Naho Ichikawa, Eri Itai, Neda Jahanshad, Hamidreza Jamalabadi, Alec J Jamieson, Andreas Jansen, Tilo Kircher, Bonnie Klimes-Dougan, Bernd Krämer, Axel Krug, Thomas M Lancaster, Elisabeth J Leehr, Meng Li, David E J Linden, Frank Macmaster, Katie L Mcmahon, Sarah E Medland, David M A Mehler, Susanne Meinert, Benson Mwangi, Igor Nenadić, Go Okada, Yasumasa Okamoto, Nils Opel, Julia-Katharina Pfarr, Edith Pomarol-Clotet, Maria J Portella, Ronny Redlich, Liesbeth Reneman, Jonathan Repple, Kai Ringwald, Elena Rodriguez-Cano, Pedro G P Rosa, Matthew D Sacchet, Philipp G Sämann, Raymond Salvador, Anouk Schrantee, Hotaka Shinzato, Kang Sim, Egle Simulionyte, Jair C Soares, Dan J Stein, Frederike Stein, Benjamin Straube, Lachlan T Strike, Florian Thomas-Odenthal, Sophia I Thomopoulos, Paul M Thompson, Marie-Jose Van Tol, Paula Usemann, Aslihan Uyar, Nic Van Der Wee, Steven Van Der Werff, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Sarah Whittle, Katharina Wittfeld, Adrian Wroblewski, Mon-Ju Wu, Tony T Yang, Giovana B Zunta-Soares, Dick J Veltman, Lianne Schmaal, Laura S Van Velzen

Faculty, Staff and Student Publications

The understanding of how antidepressant (AD) use is associated with brain structure in individuals with major depressive disorder (MDD) remains incomplete. We aimed to examine the association between AD medication use and brain morphology in relation to age and sex by pooling structural neuroimaging and clinical data from 32 cohorts within the ENIGMA-MDD working group. Interaction effects of group (2076 cases with current AD use (AD), 1495 cases not currently taking AD (nAD) and 5125 healthy controls (HC)) with age and sex, and main effects of group on regional brain structure (cortical surface area and thickness, and subcortical volume) were …

Chemotherapy Alone For Stage Ii-Iva Laryngeal Squamous Cell Carcinoma: A 20-Year Follow-Up, Mateus Trinconi Cunha, Matheus Sewastjanow-Silva, F Christopher Holsinger, Adam S Garden, Adel K El-Naggar, Jan Lewin, J Jack Lee, Fadlo R Khuri, Eduardo M Diaz, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Current treatment options for nonmetastatic laryngeal squamous cell carcinoma include radiotherapy, chemoradiotherapy, and surgery, which can result in significant morbidity. This study reports the 20-year outcomes of a single-modality chemotherapy as a larynx preservation strategy in patients with stage II-IVa laryngeal squamous cell carcinoma (LSCC).

Methods: In this single-institution, single-arm, prospective clinical trial, 31 patients with stage II-IVa LSCC received three or four cycles of paclitaxel, ifosfamide, and a platinum agent (TIP). Patients with a pathologic complete response (pCR) by biopsy assessment received three additional cycles without local therapy. Patients with a partial response underwent conservation laryngeal surgery (CLS). …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

The Kiva System Versus Balloon Kyphoplasty For Vertebral Compression Fracture: A Meta-Analysis Of Randomized Control Trials, Humaid Al Farii, Nikhil Gattu, Caleb M Yeung, Christopher A Alvarez-Breckenridge, Robert Y North, Laurence D Rhines, Justin E Bird, Shalin S Patel

Faculty, Staff and Student Publications

Background: Vertebral compression fractures (VCFs) are the most common type of vertebral body fracture. The Kiva VCF Treatment System is a relatively novel technique to manage VCFs. The aim of this study was to compare the efficacy of Kiva versus standard Balloon Kyphoplasty (BK) through evaluation of published randomized controlled trials (RCTs).

Methods: This study was performed following the guidelines for PRISMA. We performed a systematic literature search using PubMed and MEDLINE in June 2023. The search keywords were "Kiva" and "Kyphoplasty" which yielded a total of 112 articles. Outcome measures included pain, measured through the Visual Analogue Scale (VAS) …