Medicine and Health Sciences Commons^™

Interactive Associations Of Eczema With Glutathione S-Transferase Genes In Relation To Autism Spectrum Disorder And Its Severity In Jamaican Children, Sepideh Saroukhani, Maureen Samms-Vaughan, Jan Bressler, Minjae Lee, Courtney Byrd-Williams, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Comorbidity of eczema with autism spectrum disorder (ASD) is increasing. We investigated the associations of eczema and its possible interaction with polymorphisms in glutathione S-transferase (GST) genes in relation to ASD and ASD severity.

METHOD: Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of eczema with GST genes in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domain-specific comparison scores (CSs) by fitting general linear …

Parametric Delineation Uncertainties Contouring (Pduc) Modeling On Ct Scans Of Prostate Cancer Patients, Vi Ly, Lizhong Liu, Carlos Cardenas, Sean Maroongroge, Brian De, Daniel El Basha, Laurence Court, Xi Luo

Faculty, Staff and Student Publications

PURPOSE: Variability in contouring contributes to large variations in radiation therapy planning and treatment outcomes. The development and testing of tools to automatically detect contouring errors require a source of contours that includes well-understood and realistic errors. The purpose of this work was to develop a simulation algorithm that intentionally injects errors of varying magnitudes into clinically accepted contours and produces realistic contours with different levels of variability.

METHODS: We used a dataset of CT scans from 14 prostate cancer patients with clinician-drawn contours of the regions of interest (ROI) of the prostate, bladder, and rectum. Using our newly developed …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Stress-Induced Changes In Autonomic Reactivity Vary With Adolescent Violence Exposure And Resting-State Functional Connectivity, Heather E Dark, Nathaniel G Harnett, Adam M Goodman, Muriah D Wheelock, Sylvie Mrug, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, David C Knight

Faculty, Staff and Student Publications

Exposure to violence during childhood can lead to functional changes in brain regions that are important for emotion expression and regulation, which may increase susceptibility to internalizing disorders in adulthood. Specifically, childhood violence exposure can disrupt the functional connectivity among brain regions that include the prefrontal cortex (PFC), hippocampus, and amygdala. Together, these regions are important for modulating autonomic responses to stress. However, it is unclear to what extent changes in brain connectivity relate to autonomic stress reactivity and how the relationship between brain connectivity and autonomic responses to stress varies with childhood violence exposure. Thus, the present study examined …

Posttransplant Outcomes For Alcohol-Associated Liver Disease During The Covid-19 Pandemic, Karthik Goli, Peter Lymberopoulos, Ronald Samuel, Anjiya Shaikh, Nisha Parakadavil, Donghee Kim, Aijaz Ahmed, John A Goss, Abbas Rana, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

No abstract provided.

Co-Operative Roles Of Il-4rα And Il-13rα1 In The Progression Of Ovarian Carcinomas And The Survival Of Ovarian Carcinoma Patients, Won Ku Choi, Usama Khamis Hussein, Asmaa Gamal Ahmed, Junyue Zhang, Kyoung Min Kim, Ae Ri Ahn, Ho Sung Park, See-Hyoung Park, Dong Hyu Cho, Kyu Yun Jang

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Epidemiology Of Nonsyndromic, Orofacial C/Lefts In Texas: Differences By Cleft Type And Presence Of Additional Defects, Maria Luisa Navarro Sanchez, Michael D Swartz, Peter H Langlois, Mark A Canfield, A J Agopian

Faculty, Staff and Student Publications

To describe the current epidemiology of nonsyndromic cleft palate alone (CP) and cleft lip with or without cleft palate (CL ± P) in Texas and examine differences in the characteristics of infants with CP and CL ± P based on the presence/absence of additional defects. We used data from the Texas Birth Defects Registry, a statewide active birth defect surveillance system, from 1815 cases with CP and 5066 with CL ± P, without a syndrome diagnosis (1999-2014 deliveries). All live births in Texas were used for comparison. Poisson regression was used to calculate crude and adjusted prevalence ratios (aPR) for …

A Mendelian Randomization Study Of Genetic Liability To Post-Traumatic Stress Disorder And Risk Of Ischemic Stroke, Opeyemi Soremekun, Clarisse Musanabaganwa, Annette Uwineza, Maddalena Ardissino, Skanda Rajasundaram, Agaz H Wani, Stefan Jansen, Jean Mutabaruka, Eugene Rutembesa, Chisom Soremekun, Cisse Cheickna, Mamadou Wele, Joseph Mugisha, Oyekanmi Nash, Eugene Kinyanda, Dorothea Nitsch, Myriam Fornage, Tinashe Chikowore, Dipender Gill, Derek E Wildman, Leon Mutesa, Monica Uddin, Segun Fatumo

Faculty, Staff and Student Publications

Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk. Ancestry-specific genetic instruments of PTSD and four quantitative sub-phenotypes of PTSD, including hyperarousal, avoidance, re-experiencing, and total symptom severity score (PCL-Total) were obtained from the Million Veteran Programme (MVP) using a threshold P value (P) of <5 >× 10

Clonal Hematopoiesis Is Associated With Protection From Alzheimer's Disease, Hind Bouzid, Julia A Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, Matthew R Chrostek, Herra Ahmad, Daniel Nachun, Winnie Yao, Alexa Beiser, Alexander G Bick, Joshua C Bis, Myriam Fornage, William T Longstreth, Oscar L Lopez, Pradeep Natarajan, Bruce M Psaty, Claudia L Satizabal, Joshua Weinstock, Eric B Larson, Paul K Crane, C Dirk Keene, Sudha Seshadri, Ansuman T Satpathy, Thomas J Montine, Siddhartha Jaiswal

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P …

Prevalence Of Ddc Genotypes In Patients With Aromatic L-Amino Acid Decarboxylase (Aadc) Deficiency And In Silico Prediction Of Structural Protein Changes, Nastassja Himmelreich, Mariarita Bertoldi, Majid Alfadhel, Malak Ali Alghamdi, Yair Anikster, Xinhua Bao, Fahad A Bashiri, Bruria Ben Zeev, Giovanni Bisello, Ahmet Cevdet Ceylan, Yin-Hsiu Chien, Yew Sing Choy, Sarah H Elsea, Lisa Flint, Àngels García-Cazorla, Charul Gijavanekar, Emel Yılmaz Gümüş, Muddathir H Hamad, Burcu Hişmi, Tomas Honzik, Oya Kuseyri Hübschmann, Wuh-Liang Hwu, Salvador Ibáñez-Micó, Kathrin Jeltsch, Natalia Juliá-Palacios, Çiğdem Seher Kasapkara, Manju A Kurian, Katarzyna Kusmierska, Ning Liu, Lock Hock Ngu, John D Odom, Winnie Peitee Ong, Thomas Opladen, Mari Oppeboen, Phillip L Pearl, Belén Pérez, Roser Pons, Agnieszka Magdalena Rygiel, Tan Ee Shien, Robert Spaull, Jolanta Sykut-Cegielska, Brahim Tabarki, Trine Tangeraas, Beat Thöny, Tessa Wassenberg, Yongxin Wen, Yusnita Yakob, Jasmine Goh Chew Yin, Jiri Zeman, Nenad Blau

Faculty, Staff and Students Publications

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, …

Mathematical Analysis Of Hemoglobin Target In Univentricular Parallel Circulation, Mubbasheer Ahmed, Sebastian I Acosta, George M Hoffman, James S Tweddell, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: The hemoglobin threshold for a decision to transfuse red blood cells in univentricular patients with parallel circulation is unclear. A pediatric expertise initiative put forth a "weak recommendation" for avoiding reflexive transfusion beyond a hemoglobin of 9 g/dL. We have created a mathematical model to assess the impact of hemoglobin thresholds in patients with parallel circulation.

Methods: A univentricular circulation was mathematically modeled. We examined the impact on oxygen extraction ratios and systemic and venous oxygen saturations by varying hemoglobin levels, pulmonary to systemic blood flow ratios, and total cardiac output.

Results: Applying a total cardiac index of 6 …

The Systemic Availability Of Indispensable Amino Acids From Orally Ingested Algal And Legume Protein In Young Children At Risk Of Environmental Enteric Dysfunction, Nirupama Shivakumar, Sindhu Kashyap, Farook Jahoor, Sarita Devi, Thomas Preston, Tinku Thomas, Anura V Kurpad

Faculty, Staff and Students Publications

Background: The digestion and absorption of ingested protein may be reduced in children with environmental enteric dysfunction (EED), reducing systemic amino acid availability for protein synthesis with resultant growth faltering. This has not been directly measured in children with EED and associated growth faltering.

Objectives: To evaluate the systemic availability of algal (spirulina) and legume (mung bean) indispensable amino acids (IAAs) in children with EED.

Methods: Indian children (18-24 mo) from urban slums were assigned to EED (n = 24) or no-EED (control, n = 17) groups based on the lactulose rhamnose test, where the lactulose rhamnose ratio cutoff for …

Achieving Equity In Emergency Medicine Quality Measures Requires A Sex And Gender Lens, Ynhi T Thomas, Angela F Jarman, Nina G Faynshtayn, Greg B Buehler, Sara Andrabi, Alyson J Mcgregor

Faculty, Staff and Students Publications

BACKGROUND: Quality measures within Emergency Medicine (EM) were developed to standardize and improve care. Their development has been limited by lack of consideration of sex- and gender-based differences. Research has suggested that sex and gender can impact clinical care and treatment. Inclusion of sex and gender differences is needed to create EM quality measures that are equitable to all.

OBJECTIVE: The aim of the review is to provide a brief history of EM quality measures and the value of considering sex- and gender-based evidence in their development to ensure equity, using acute myocardial infarction (AMI) as an example.

DISCUSSION: Current …

Current Programs And Incentives To Overcome Rural Physician Shortages In The United States: A Narrative Review, Kelley Arredondo, Hilary N Touchett, Sundas Khan, Matthew Vincenti, Bradley V Watts

Faculty, Staff and Students Publications

Access to healthcare continues to be a top priority and prominent challenge in rural communities, with 20% of the total U.S. population living in rural areas while only 10% of physicians practice in rural areas. In response to physician shortages, a variety of programs and incentives have been implemented to recruit and retain physicians in rural areas; however, less is known about the types and structures of incentives that are offered in rural areas and how that compares to physician shortages. The purpose of our study is to conduct a narrative review of the literature to identify and compare current …

Artist's Statement: Foreground/Background, Tahira Scholle

Faculty, Staff and Students Publications

No abstract provided.

View-Vlu Observational Study Of The Effect Of Varithena On Wound Healing In The Treatment Of Venous Leg Ulcers., Michael Y Shao, Stuart Harlin, Beverly Chan, Kathylee Santangelo, Eri Fukaya, Julianne Stoughton, Raghu Kolluri

Heart and Vascular Articles

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates.

METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included …

Delphi Consensus On Reporting Standards In Clinical Studies For Endovascular Treatment Of Acute Iliofemoral Venous Thrombosis And Chronic Iliofemoral Venous Obstruction., Suresh Vedantham, Peter Gloviczki, Teresa L Carman, Sandra Zelman Lewis, Peter A Schneider, Saher S Sabri, Raghu Kolluri

Heart and Vascular Articles

Acute iliofemoral deep vein thrombosis and chronic iliofemoral venous obstruction cause substantial patient harm and are increasingly managed with endovascular venous interventions, including percutaneous mechanical thrombectomy and stent placement. However, studies of these treatment elements have not been designed and reported with sufficient rigor to support confident conclusions about their clinical utility. In this project, the Trustworthy consensus-based statement approach was utilized to develop, via a structured process, consensus-based statements to guide future investigators of venous interventions. Thirty statements were drafted to encompass major topics relevant to venous study description and design, safety outcome assessment, efficacy outcome assessment, and topics …

Advancing Asms With Lc-Ms/Ms For The Discovery Of Novel Pdcl2 Ligands From Dna-Encoded Chemical Library Selections, Qiuji Ye, Hassane Belabed, Yong Wang, Zhifeng Yu, Murugesan Palaniappan, Jian-Yuan Li, Stacey A Kalovidouris, Kevin R Mackenzie, Mingxing Teng, Damian W Young, Yoshitaka Fujihara, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: A safe, effective, and reversible nonhormonal male contraceptive drug is greatly needed for male contraception as well as for circumventing the side effects of female hormonal contraceptives. Phosducin-like 2 (PDCL2) is a testis-specific phosphoprotein in mice and humans. We recently found that male PDCL2 knockout mice are sterile due to globozoospermia caused by impaired sperm head formation, indicating that PDCL2 is a potential target for male contraception. Herein, our study for the first time developed a biophysical assay for PDCL2 allowing us to screen a series of small molecules, to study structure-activity relationships, and to discover two PDCL2 binders …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

Transplantation Referral Patterns For Patients With Newly Diagnosed Higher-Risk Myelodysplastic Syndromes And Acute Myeloid Leukemia At Academic And Community Sites In The Connect® Myeloid Disease Registry: Potential Barriers To Care, Benjamin Tomlinson, Marcos De Lima, Christopher R Cogle, Michael A Thompson, David L Grinblatt, Daniel A Pollyea, Rami S Komrokji, Gail J Roboz, Michael R Savona, Mikkael A Sekeres, Mehrdad Abedi, Guillermo Garcia-Manero, Sandra E Kurtin, Jaroslaw P Maciejewski, Jay L Patel, Dennis A Revicki, Tracy I George, E Dawn Flick, Pavel Kiselev, Chrystal U Louis, Irene S Degutis, Melissa Nifenecker, Harry P Erba, David P Steensma, Bart L Scott

Faculty, Staff and Student Publications

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to …

Association Of Second-Generation Antiandrogens With Cognitive And Functional Toxic Effects In Randomized Clinical Trials: A Systematic Review And Meta-Analysis, Malgorzata K Nowakowska, Rachel M Ortega, Mackenzie R Wehner, Kevin T Nead

Faculty, Staff and Student Publications

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.

Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

Data sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022).

Study selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, …

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome, Melissa R Hines, Tristan E Knight, Kevin O Mcnerney, Mark B Leick, Tania Jain, Sairah Ahmed, Matthew J Frigault, Joshua A Hill, Michael D Jain, William T Johnson, Yi Lin, Kris M Mahadeo, Gabriela M Maron, Rebecca A Marsh, Sattva S Neelapu, Sarah Nikiforow, Amanda K Ombrello, Nirav N Shah, Aimee C Talleur, David Turicek, Anant Vatsayan, Sandy W Wong, Marcela V Maus, Krishna V Komanduri, Nancy Berliner, Jan-Inge Henter, Miguel-Angel Perales, Noelle V Frey, David T Teachey, Matthew J Frank, Nirali N Shah

Faculty, Staff and Student Publications

T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) T cell therapy. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusion are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal …

Estrogen-Related Receptor Signaling In Skeletal Muscle Fitness, Danesh Sopariwala, Hao Nguyen, Vihang Narkar

Faculty, Staff and Student Publications

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On …

Plasma Cell Myeloma With Ras/Braf Mutations Is Frequently Associated With A Complex Karyotype, Advanced Stage Disease, And Poorer Prognosis, Nianyi Li, Pei Lin, Zhuang Zuo, M James You, Wen Shuai, Robert Orlowski, Elisabet E Manasanch, Shaoying Li, Jie Xu, Sofia Garces, Fatima Zahra Jelloul, Zhenya Tang, Wei Wang, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

BACKGROUND: Mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high-risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results.

METHODS: We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF-mutated myeloma, and compare with 79 patients without any mutations.

RESULTS: We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF-mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and …

Compensation Cycle Consistent Generative Adversarial Networks (Comp-Gan) For Synthetic Ct Generation From Mr Scans With Truncated Anatomy, Yao Zhao, He Wang, Cenji Yu, Laurence E Court, Xin Wang, Qianxia Wang, Tinsu Pan, Yao Ding, Jack Phan, Jinzhong Yang

Faculty, Staff and Student Publications

BACKGROUND: MR scans used in radiotherapy can be partially truncated due to the limited field of view (FOV), affecting dose calculation accuracy in MR-based radiation treatment planning.

PURPOSE: We proposed a novel Compensation-cycleGAN (Comp-cycleGAN) by modifying the cycle-consistent generative adversarial network (cycleGAN), to simultaneously create synthetic CT (sCT) images and compensate the missing anatomy from the truncated MR images.

METHODS: Computed tomography (CT) and T1 MR images with complete anatomy of 79 head-and-neck patients were used for this study. The original MR images were manually cropped 10-25 mm off at the posterior head to simulate clinically truncated MR images. Fifteen …

Patient-Reported Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Michael Roth

Faculty, Staff and Student Publications

BACKGROUND: Radiation therapy (RT) is a common treatment for adolescents and young adults (AYAs, 15-39 years old) with cancer; however, it may cause toxicities that affect health-related quality-of-life (HRQOL). Thus, we assessed HRQOL in AYAs before, during, and after RT.

METHODS: We identified 265 AYAs who completed HRQOL PROMIS® surveys before (n = 87), during (n = 84), or after (n = 94) RT. Higher PROMIS® score represents more of the concept. Mean scores were compared to the general US population and minimally important differences (MIDs) were used to evaluate the impact of cancer on HRQOL. Linear regression modeling was …

Pontocerebellar Hypoplasia Associated With Parg183trp Homozygous Variant In Exosc1 Gene: A Case Report, Nadirah S Damseh, Ali N Obeidat, Khondakar Sayef Ahammed, Motee Al-Ashhab, Motee Abu Awad, Ambro Van Hoof

Faculty, Staff and Student Publications

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and …

Emerging Signaling Regulation Of Sinoatrial Node Dysfunction, Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND.

RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), …

Associations Between Kir/Kir-Ligand Genotypes And Clinical Outcome For Patients With Advanced Solid Tumors Receiving Bempeg Plus Nivolumab Combination Therapy In The Pivot-02 Trial, A S Feils, A K Erbe, J Birstler, K Kim, U Hoch, S L Currie, T Nguyen, D Yu, A O Siefker-Radtke, N Tannir, S M Tolaney, A Diab, P M Sondel

Faculty, Staff and Student Publications

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with …

Eliminating Breast Surgery For Invasive Cancer With Exceptional Response To Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint, Helen M Johnson, Vicente Valero, Wei T Yang, Benjamin D Smith, Savitri Krishnamurthy, Yu Shen, Heather Lin, Anthony Lucci, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

Background: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

Study design: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with < 2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

Results: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were …