Genetic Phenomena Commons^™

Dietary Intake And Quality Among Stroke Survivors: Nhanes 1999-2018, Erika R Zoellner, Mindy A Patterson, Anjail Z Sharrief, Sean I Savitz, Wesley J Tucker, Derek C Miketinas

Faculty, Staff and Student Publications

Background: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited.

Objectives: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke.

Methods: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of …

Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman

Faculty, Staff and Student Publications

No abstract provided.

Characteristics And Outcomes Of Patients With Chronic Myeloid Leukemia And T315i Mutation Treated In The Pre- And Post-Ponatinib Era, Fadi G Haddad, Koji Sasaki, Aram Bidikian, Ghayas C Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Patients with chronic myeloid leukemia (CML) and T315I mutation generally have a poor prognosis. Their outcome in the post-ponatinib era remains unclear. We reviewed patients with CML in chronic (CP) or accelerated phase (AP) who developed a T315I mutation between March 15, 2004, and July 26, 2022. Patients were divided into CP, AP, or blastic phase (BP) at the time of mutation detection. Overall survival (OS) was defined from the time of mutation detection to the date of death or last follow-up. We identified a total of 107 patients: 54 (51%) in CP, 14 (13%) in AP, and 39 (36%) …

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …

Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang

Faculty, Staff and Student Publications

Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments …

Local Continual Reassessment Methods For Dose Finding And Optimization In Drug-Combination Trials, Jingyi Zhang, Fangrong Yan, Nolan A Wages, Ruitao Lin

Faculty, Staff and Student Publications

Due to the limited sample size and large dose exploration space, obtaining a desirable dose combination is a challenging task in the early development of combination treatments for cancer patients. Most existing designs for optimizing the dose combination are model-based, requiring significant efforts to elicit parameters or prior distributions. Model-based designs also rely on intensive model calibration and may yield unstable performance in the case of model misspecification or sparse data. We propose to employ local, underparameterized models for dose exploration to reduce the hurdle of model calibration and enhance the design robustness. Building upon the framework of the partial …

Lurbinectedin In Patients With Pretreated Endometrial Cancer: Results From A Phase 2 Basket Clinical Trial And Exploratory Translational Study, Rebecca Kristeleit, Alexandra Leary, Jean Pierre Delord, Victor Moreno, Ana Oaknin, Daniel Castellano, Geoffrey I Shappiro, Cristian Fernández, Carmen Kahatt, Vicente Alfaro, Mariano Siguero, Daniel Rueda, Ali Zeaiter, Ahmad Awada, Ana Santaballa, Khalil Zaman, Jalid Sehouli, Vivek Subbiah

Faculty, Staff and Student Publications

Second-line treatment of endometrial cancer is an unmet medical need. Lurbinectedin showed promising antitumor activity in a phase I study in combination with doxorubicin in advanced endometrial cancer. This phase 2 Basket trial evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 73 patients with pretreated endometrial cancer. The primary endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and an exploratory translational study. Confirmed complete (CR) and partial response (PR) was reported in two and six patients, respectively (ORR …

Diagnosis Of Chronic Pancreatitis Using Semi-Quantitative Mri Features Of The Pancreatic Parenchyma: Results From The Multi-Institutional Minimap Study, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls.

Methods: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) …

Circulating Short Chain Fatty Acids And Fatigue In Patients With Head And Neck Cancer: A Longitudinal Prospective Study, Canhua Xiao, Veronika Fedirko, Henry Claussen, H Richard Johnston, Gang Peng, Sudeshna Paul, Kristal M Maner-Smith, Kristin A Higgins, Dong M Shin, Nabil F Saba, Evanthia C Wommack, Deborah W Bruner, Andrew H Miller

Faculty, Staff and Student Publications

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = …

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Controversy And Consensus On The Management Of Elevated Sperm Dna Fragmentation In Male Infertility: A Global Survey, Current Guidelines, And Expert Recommendations, Ala'a Farkouh, Ashok Agarwal, Taha Abo-Almagd Abdel-Meguid Hamoda, Parviz Kavoussi, Ramadan Saleh, Armand Zini, Mohamed Arafa, Ahmed M Harraz, Murat Gul, Vilvapathy Senguttuvan Karthikeyan, Damayanthi Durairajanayagam, Amarnath Rambhatla, Florence Boitrelle, Eric Chung, Ponco Birowo, Tuncay Toprak, Ramy Abou Ghayda, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Fotios Dimitriadis, Giorgio I Russo, Ioannis Sokolakis, Taymour Mostafa, Konstantinos Makarounis, Imad Ziouziou, Shinnosuke Kuroda, Marion Bendayan, Raneen Sawaid Kaiyal, Andrian Japari, Mara Simopoulou, Lucia Rocco, Nicolas Garrido, Nazim Gherabi, Kadir Bocu, Oguzhan Kahraman, Tan V Le, Christine Wyns, Kelton Tremellen, Selcuk Sarikaya, Sheena Lewis, Donald P Evenson, Edmund Ko, Aldo E Calogero, Fahmi Bahar, Marlon Martinez, Andrea Crafa, Quang Nguyen, Rafael F Ambar, Giovanni Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alarbid, Akira Tsujimura, Alireza Kheradmand, Christina Anagnostopoulou, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Germar-Michael Pinggera, Priyank Kothari, Nasser Mogharabian, Sava Micic, Sheryl Homa, Sara Darbandi, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Marjan Sabbaghian, Wael Ibrahim, Ryan P Smith, Christopher Chee Kong Ho, Jean De La Rosette, Ahmed I El-Sakka, Mirko Preto, Cătălina Zenoaga-Barbăroșie, Saad Mohammed Abumelha, Aykut Baser, Kaan Aydos, Liliana Ramirez-Dominguez, Vijay Kumar, Teng Aik Ong, Tiago Cesar Mierzwa, Ricky Adriansjah, Saleem A Banihani, Kasonde Bowa, Shinichiro Fukuhara, Marcelo Rodriguez Peña, Mohamad Moussa, Umut Çağın Ari, Chak-Lam Cho, Nicholas N Tadros, Muhammet Rasit Ugur, Edouard Amar, Marco Falcone, Frederic Romain Santer, Arif Kalkanli, Keshab Kumar Karna, Kareim Khalafalla, Ranjit B Vishwakarma, Federica Finocchi, Carlo Giulioni, Erman Ceyhan, Gökhan Çeker, Chadi Yazbeck, Osvaldo Rajmil, Mehmet Yilmaz, Baris Altay, Trenton L Barrett, Kay Seong Ngoo, Shubhadeep Roychoudhury, Gianmaria Salvio, Haocheng Lin, Ates Kadioglu, Massimiliano Timpano, Tomer Avidor-Reiss, Lukman Hakim, Puneet Sindhwani, Giorgio Franco, Rajender Singh, Filippo Giacone, Mikhail Ruzaev, Raghavender Kosgi, Nikolaos Sofikitis, Ayad Palani, Gokhan Calik, Deniz Kulaksız, Davor Jezek, Manaf Al Hashmi, Panagiotis Drakopoulos, Huda Omran, Sofia Leonardi, Ciler Celik-Ozenci, Nur Dokuzeylül Güngör, Jonathan Ramsay, Toshiyasu Amano, Emrullah Sogutdelen, Gede Wirya Kusuma Duarsa, Koji Chiba, Sunil Jindal, Missy Savira, Luca Boeri, Edson Borges, Deepak Gupte, Fatih Gokalp, Guadalupe Hernández Hebrard, Suks Minhas, Rupin Shah, Global Andrology Forum

Faculty, Staff and Student Publications

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.

Materials and methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate …

Regression Analysis Of General Mixed Recurrent Event Data, Ryan Sun, Dayu Sun, Liang Zhu, Jianguo Sun

Faculty, Staff and Student Publications

In modern biomedical datasets, it is common for recurrent outcomes data to be collected in an incomplete manner. More specifically, information on recurrent events is routinely recorded as a mixture of recurrent event data, panel count data, and panel binary data; we refer to this structure as general mixed recurrent event data. Although the aforementioned data types are individually well-studied, there does not appear to exist an established approach for regression analysis of the three component combination. Often, ad-hoc measures such as imputation or discarding of data are used to homogenize records prior to the analysis, but such measures lead …

Clinical Genome Sequencing: Three Years’ Experience At A Tertiary Children’S Hospital, Runjun D Kumar, Lisa F Saba, Haley Streff, Chad A Shaw, Elizabeth Mizerik, Matthew T Snyder, Dolores Lopez-Terrada, Jennifer Scull

Duncan NRI Faculty and Staff Publications

Purpose: Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in nonresearch settings remains limited. Texas Children's Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study GS utilization, possibilities for test optimization, and testing outcomes.

Methods: We retrospectively reviewed GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions.

Results: The diagnostic yield over 97 admitted patients was 35%. The majority of GS …

Meeting The Demand For Fertility Services: The Present And Future Of Reproductive Endocrinology And Infertility In The United States, Eduardo Hariton, Ruben Alvero, Micah J Hill, Jennifer E Mersereau, Shana Perman, David Sable, Fiona Wang, Geoffrey David Adamson, Christos Coutifaris, Latasha B Craig, Pardis Hosseinzadeh, Anthony N Imudia, Erica B Johnstone, Ruth B Lathi, Paul C Lin, Erica E Marsh, Michele Munch, Gloria Richard-Davis, Lauren W Roth, Amy K Schutt, Kim Thornton, Lauren Verrilli, Rachel S Weinerman, Steven L Young, Kate Devine

Faculty, Staff and Students Publications

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action …

Dimensionality Reduction For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Mais Al Taie, Joshua P Yung, Tucker J Netherton, Ankit B Patel, Kristy K Brock

Faculty, Staff and Student Publications

Clinically-deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these models do tend to perform well in most instances, which could exacerbate automation bias. Therefore, it is critical to detect out-of-distribution images at inference to warn the clinicians that the model likely failed. This work applies the Mahalanobis distance post hoc to the bottleneck features of a Swin UNETR model that segments the liver on T1-weighted magnetic resonance imaging. By reducing the dimensions of the bottleneck features with principal component analysis, images the model failed on were detected …

A Ck2 And Sumo-Dependent, Pml Nb-Involved Regulatory Mechanism Controlling Blm Ubiquitination And G-Quadruplex Resolution, Shichang Liu, Erin Atkinson, Adriana Paulucci-Holthauzen, Bin Wang

Faculty, Staff and Student Publications

The Boom syndrome helicase (BLM) unwinds a variety of DNA structures such as Guanine (G)-quadruplex. Here we reveal a role of RNF111/Arkadia and its paralog ARKL1, as well as Promyelocytic Leukemia Nuclear Bodies (PML NBs), in the regulation of ubiquitination and control of BLM protein levels. RNF111 exhibits a non-canonical SUMO targeted E3 ligase (STUBL) activity targeting BLM ubiquitination in PML NBs. ARKL1 promotes RNF111 localization to PML NBs through SUMO-interacting motif (SIM) interaction with SUMOylated RNF111, which is regulated by casein kinase 2 (CK2) phosphorylation of ARKL1 at a serine residue near the ARKL1 SIM domain. Upregulated BLM in …

Integrated Molecular And Multiparametric Mri Mapping Of High-Grade Glioma Identifies Regional Biologic Signatures, Leland S Hu, Fulvio D'Angelo, Taylor M Weiskittel, Francesca P Caruso, Shannon P Fortin Ensign, Mylan R Blomquist, Matthew J Flick, Lujia Wang, Christopher P Sereduk, Kevin Meng-Lin, Gustavo De Leon, Ashley Nespodzany, Javier C Urcuyo, Ashlyn C Gonzales, Lee Curtin, Erika M Lewis, Kyle W Singleton, Timothy Dondlinger, Aliya Anil, Natenael B Semmineh, Teresa Noviello, Reyna A Patel, Panwen Wang, Junwen Wang, Jennifer M Eschbacher, Andrea Hawkins-Daarud, Pamela R Jackson, Itamar S Grunfeld, Christian Elrod, Gina L Mazza, Sam C Mcgee, Lisa Paulson, Kamala Clark-Swanson, Yvette Lassiter-Morris, Kris A Smith, Peter Nakaji, Bernard R Bendok, Richard S Zimmerman, Chandan Krishna, Devi P Patra, Naresh P Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej M Mrugala, Alyx B Porter, Scott C Beeman, Todd R Jensen, Kathleen M Schmainda, Yuxiang Zhou, Leslie C Baxter, Christopher L Plaisier, Jing Li, Hu Li, Anna Lasorella, C Chad Quarles, Kristin R Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L Tran

Faculty, Staff and Student Publications

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate …

National Survey On The Availability Of Oncology Palliative Care Services At Tertiary General And Cancer Hospitals In China, Xiaomei Li, Xin Shelley Wang, Haili Huang, Miao Liu, Yinan Wu, Jiaojiao Qiu, Boran Zhang, Linhong Cui, David Hui

Faculty, Staff and Student Publications

Background: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China.

Methods: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service.

Results: Most responders …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Pca-Clf: A Classifier Of Prostate Cancer Patients Into Patients With Indolent And Aggressive Tumors Using Machine Learning, Yashwanth Karthik Kumar Mamidi, Tarun Karthik Kumar Mamidi, Md Wasi Ul Kabir, Jiande Wu, Md Tamjidul Hoque, Chindo Hicks

School of Medicine Faculty Publications

A critical unmet medical need in prostate cancer (PCa) clinical management centers around distinguishing indolent from aggressive tumors. Traditionally, Gleason grading has been utilized for this purpose. However, tumor classification using Gleason Grade 7 is often ambiguous, as the clinical behavior of these tumors follows a variable clinical course. This study aimed to investigate the application of machine learning techniques (ML) to classify patients into indolent and aggressive PCas. We used gene expression data from The Cancer Genome Atlas and compared gene expression levels between indolent and aggressive tumors to identify features for developing and validating a range of ML …