Genetic Phenomena Commons^™

Integrated Pathologic Score Effectively Stratifies Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreaticoduodenectomy, Aaron J Sohn, Mehran Taherian, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Jeffrey E Lee, Naruhiko Ikoma, Asif Rashid, Robert A Wolff, Dan Zhao, Eugene J Koay, Ryan Sun, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Pathologic parameters of treated PDAC, including tumor (ypT) and lymph node (ypN) stage, and tumor response grading (TRG) are important prognostic factors in this group of patients. To our knowledge, a multifactorial prognostic score combining pathologic features including ypT, ypN, and TRG in treated PDAC patients has not been reported. Our cohort consisted of 398 PDAC patients who received neoadjuvant therapy and underwent pancreaticoduodenectomy at our institution. All pancreaticoduodenectomy specimens were grossly and microscopically evaluated using a standard protocol. The integrated pathologic score (IPS) was calculated as …

Data Partitioning And Statistical Considerations For Association Of Radiomic Features To Biological Underpinnings: What Is Needed, Michael A Jacobs

Faculty, Staff and Student Publications

No abstract provided.

Patient Radiation Doses In Interventional Radiology Procedures: Comparison Of Fluoroscopy Dose Indices Between The American College Of Radiology Dose Index Registry-Fluoroscopy Pilot And The Radiation Doses In Interventional Radiology Study, A Kyle Jones, Kevin A Wunderle, Tom Fruscello, Michael Simanowith, Brendan Cline, Shalmali Dharmadhikari, Xinhui Duan, Jeremy C Durack, David Hirschl, Don-Soo Kim, Usman Mahmood, Steve D Mann, Charles Martin, Zeyad Metwalli, Jeffrey M Moirano, Rebecca A Neill, Janice Newsome, Horacio Padua, Alan H Schoenfeld, Donald L Miller

Faculty, Staff and Student Publications

Purpose: To compare radiation dose index distributions for fluoroscopically guided interventions in interventional radiology from the American College of Radiology (ACR) Fluoroscopy Dose Index Registry (DIR-Fluoro) pilot to those from the Radiation Doses in Interventional Radiology (RAD-IR) study.

Materials and methods: Individual and grouped ACR Common identification numbers (procedure types) from the DIR-Fluoro pilot were matched to procedure types in the RAD-IR study. Fifteen comparisons were made. Distribution parameters, including the 10th, 25th, 50th, 75th, and 95th percentiles, were compared for fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA). Two derived indices were computed using median …

Patient Radiation Doses In Ir Procedures: The American College Of Radiology Dose Index Registry-Fluoroscopy Pilot, A Kyle Jones, Kevin A Wunderle, Tom Fruscello, Michael Simanowith, Brendan Cline, Shalmali Dharmadhikari, Xinhui Duan, Jeremy C Durack, David Hirschl, Don-Soo Kim, Usman Mahmood, Steve D Mann, Charles Martin, Zeyad Metwalli, Jeffrey M Moirano, Rebecca A Neill, Janice Newsome, Horacio Padua, Alan H Schoenfeld, Donald L Miller

Faculty, Staff and Student Publications

Purpose: To update normative data on fluoroscopy dose indices in the United States for the first time since the Radiation Doses in Interventional Radiology study in the late 1990s.

Materials and methods: The Dose Index Registry-Fluoroscopy pilot study collected data from March 2018 through December 2019, with 50 fluoroscopes from 10 sites submitting data. Primary radiation dose indices including fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA) were collected for interventional radiology fluoroscopically guided interventional (FGI) procedures. Clinical facility procedure names were mapped to the American College of Radiology (ACR) common procedure lexicon. Distribution parameters including …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Letter To The Editor: Quality Criteria For Computational Models Predicting Individual Outcomes In Car-T Cell Therapy, Anna M Mc Laughlin, Cassian Yee

Faculty, Staff and Student Publications

No abstract provided.

Long-Term Outcomes Of Allogeneic Hematopoietic Cell Transplantation In Patients With Newly Diagnosed Multiple Myeloma, Aimaz Afrough, Leonard C Alsfeld, Denái R Milton, Ruby Delgado, Uday R Popat, Yago Nieto, Partow Kebriaei, Betul Oran, Neeraj Saini, Samer Srour, Chitra Hosing, Faisal H Cheema, Sairah Ahmed, Elisabet E Manasanch, Hans C Lee, Gregory P Kaufman, Krina K Patel, Donna M Weber, Robert Z Orlowski, Chelsea C Pinnix, Bouthaina S Dabaja, Sheeba K Thomas, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Qaiser Bashir

Faculty, Staff and Student Publications

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least …

Prediction Of Survival With Lower Intensity Therapy Among Older Patients With Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval G Daver, Elias J Jabbour, Guillermo Garcia-Manero, Sanam Loghavi, Keyur P Patel, Guillermo Montalban-Bravo, Lucia Masarova, Courtney D Dinardo, Hagop M Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to develop a prognostic model for survival in older/unfit patients with newly diagnosed acute myeloid leukemia (AML) who were treated with lower-intensity chemotherapy regimens.

METHODS: The authors reviewed all older/unfit patients with newly diagnosed AML who received lower-intensity chemotherapy from 2000 until 2020 at their institution. A total of 1462 patients were included. They were divided (3:1 basis) into a training (n = 1088) and a validation group (n = 374).

RESULTS: In the training cohort of 1088 patients (median age, 72 years), the multivariate analysis identified 11 consistent independent adverse factors associated …

The Outcomes Of Patients With Chronic Myeloid Leukemia Treated With Third-Line Bcr::Abl1 Tyrosine Kinase Inhibitors, Elias J Jabbour, Koji Sasaki, Fadi G Haddad, Ghayas C Issa, Guillermo Garcia-Manero, Tapan M Kadia, Nitin Jain, Musa Yilmaz, Courtney D Dinardo, Keyur P Patel, Rashmi Kanagal-Shamanna, Richard Champlin, Issa F Khouri, Sara Dellasala, Sherry A Pierce, Hagop Kantarjian

Faculty, Staff and Student Publications

The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib …

Tissue Specificity And Spatio-Temporal Dynamics Of The P53 Transcriptional Program, Vinod Pant, Chang Sun, Guillermina Lozano

Faculty, Staff and Student Publications

Transcription factors regulate hundreds of genes and p53 is no exception. As a stress responsive protein, p53 transactivates an array of downstream targets which define its role in maintaining physiological functions of cells/tissues. Despite decades of studies, our understanding of the p53 in vivo transcriptional program is still incomplete. Here we discuss some of the physiological stressors that activate p53, the pathological and physiological implications of p53 activation and the molecular profiling of the p53 transcriptional program in maintaining tissue homeostasis. We argue that the p53 transcriptional program is spatiotemporally regulated in a tissue-specific manner and define a p53 target …

Advancing Car T Cell Therapy Through The Use Of Multidimensional Omics Data, Jingwen Yang, Yamei Chen, Ying Jing, Michael R Green, Leng Han

Faculty, Staff and Student Publications

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, …

Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma Patients In Complete Metabolic Response, Andrew P Jallouk, Sushanth Gouni, Jason Westin, Lei Feng, Haleigh Mistry, Raphael E Steiner, Jinsu James, Mansoor Noorani, Sandra Horowitz, Nahum Puebla-Osorio, Luis E Fayad, Swaminathan P Iyer, Misha Hawkins, Christopher R Flowers, Sairah Ahmed, Loretta J Nastoupil, Partow Kebriaei, Elizabeth J Shpall, Sattva S Neelapu, Yago Nieto, Paolo Strati

Faculty, Staff and Student Publications

No abstract provided.

Inconsistent Partitioning And Unproductive Feature Associations Yield Idealized Radiomic Models, Mishka Gidwani, Ken Chang, Jay Biren Patel, Katharina Viktoria Hoebel, Syed Rakin Ahmed, Praveer Singh, Clifton David Fuller, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Background Radiomics is the extraction of predefined mathematic features from medical images for the prediction of variables of clinical interest. While some studies report superlative accuracy of radiomic machine learning (ML) models, the published methodology is often incomplete, and the results are rarely validated in external testing data sets. Purpose To characterize the type, prevalence, and statistical impact of methodologic errors present in radiomic ML studies. Materials and Methods Radiomic ML publications were reviewed for the presence of performance-inflating methodologic flaws. Common flaws were subsequently reproduced with randomly generated features interpolated from publicly available radiomic data sets to demonstrate the …

A Deep-Learning-Based Dose Verification Tool Utilizing Fluence Maps For A Cobalt-60 Compensator-Based Intensity-Modulated Radiation Therapy System, Kyuhak Oh, Mary P Gronberg, Tucker J Netherton, Bishwambhar Sengupta, Carlos E Cardenas, Laurence E Court, Eric C Ford

Faculty, Staff and Student Publications

Background and purpose: A novel cobalt-60 compensator-based intensity-modulated radiation therapy (IMRT) system was developed for a resource-limited environment but lacked an efficient dose verification algorithm. The aim of this study was to develop a deep-learning-based dose verification algorithm for accurate and rapid dose predictions.

Materials and methods: A deep-learning network was employed to predict the doses from static fields related to beam commissioning. Inputs were a cube-shaped phantom, a beam binary mask, and an intersecting volume of the phantom and beam binary mask, while output was a 3-dimensional (3D) dose. The same network was extended to predict patient-specific doses for …

Coevolutionary Signals In Metabotropic Glutamate Receptors Capture Residue Contacts And Long-Range Functional Interactions, Eunna Huh, Melina A Agosto, Theodore G Wensel, Olivier Lichtarge

Faculty, Staff and Students Publications

Upon ligand binding to a G protein-coupled receptor, extracellular signals are transmitted into a cell through sets of residue interactions that translate ligand binding into structural rearrangements. These interactions needed for functions impose evolutionary constraints so that, on occasion, mutations in one position may be compensated by other mutations at functionally coupled positions. To quantify the impact of amino acid substitutions in the context of major evolutionary divergence in the G protein-coupled receptor subfamily of metabotropic glutamate receptors (mGluRs), we combined two phylogenetic-based algorithms, Evolutionary Trace and covariation Evolutionary Trace, to infer potential structure-function couplings and roles in mGluRs. We …

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Language: Its Origin And Ongoing Evolution, Ilia Markov, Kseniia Kharitonova, Elena L Grigorenko

Faculty, Staff and Students Publications

With the present paper, we sought to use research findings to illustrate the following thesis: the evolution of language follows the principles of human evolution. We argued that language does not exist for its own sake, it is one of a multitude of skills that developed to achieve a shared communicative goal, and all its features are reflective of this. Ongoing emerging language adaptations strive to better fit the present state of the human species. Theories of language have evolved from a single-modality to multimodal, from human-specific to usage-based and goal-driven. We proposed that language should be viewed as a …

Venetoclax For Acute Myeloid Leukemia In Pediatric Patients: A Texas Medical Center Experience, Adriana Trabal, Amber Gibson, Jiasen He, David Mccall, Michael Roth, Cesar Nuñez, Miriam Garcia, Meredith Buzbee, Laurie Toepfer, Aram Bidikian, Naval Daver, Tapan Kadia, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Courtney D Dinardo, Guillermo Montalban Bravo, Sofia Garces, Andrea Marcogliese, Hana Paek, Zoann Dreyer, Julienne Brackett, Michele Redell, Joanna Yi, Guillermo Garcia-Manero, Marina Konopleva, Alexandra Stevens, Branko Cuglievan

Faculty, Staff and Student Publications

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), …

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …