Digital Commons Network^™

A Non-Coding Insertional Mutation Of Grhl2 Causes Gene Over-Expression And Multiple Structural Anomalies Including Cleft Palate, Spina Bifida And Encephalocele, Georgia Pitsava, Marcia L Feldkamp, Nathan Pankratz, John Lane, Denise M Kay, Kristin M Conway, Charlotte Hobbs, Gary M Shaw, Jennita Reefhuis, Mary M Jenkins, Lynn M Almli, Cynthia Moore, Martha Werler, Marilyn L Browne, Chris Cunniff, Andrew F Olshan, Faith Pangilinan, Lawrence C Brody, Robert J Sicko, Richard H Finnell, Michael J Bamshad, Daniel Mcgoldrick, Deborah A Nickerson, James C Mullikin, Paul A Romitti, James L Mills

Faculty, Staff and Students Publications

BACKGROUND: Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA.

METHODS: Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child-parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child-father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced.

RESULTS: Three children had heterozygous missense variants in ID1 (Inhibitor of DNA …

Retinal Organoids Derived From Rhesus Macaque Ipscs Undergo Accelerated Differentiation Compared To Human Stem Cells, Antonio Jacobo Lopez, Sangbae Kim, Xinye Qian, Jeffrey Rogers, J Timothy Stout, Sara M Thomasy, Anna La Torre, Rui Chen, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: To compare the timing and efficiency of the development of Macaca mulatta, a nonhuman primate (NHP), induced pluripotent stem cell (rhiPSC) derived retinal organoids to those derived from human embryonic stem cells (hESCs).

RESULTS: Generation of retinal organoids was achieved from both human and several NHP pluripotent stem cell lines. All rhiPSC lines resulted in retinal differentiation with the formation of optic vesicle-like structures similar to what has been observed in hESC retinal organoids. NHP retinal organoids had laminated structure and were composed of mature retinal cell types including cone and rod photoreceptors. Single-cell RNA sequencing was conducted at …

Single-Cell Transcriptional Profiling Of Murine Conjunctival Immune Cells Reveals Distinct Populations Expressing Homeostatic And Regulatory Genes, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Immune cells in the exposed conjunctiva mucosa defend against environmental and microbial stresses. Expression profiling by single-cell RNA sequencing was performed to identify conjunctival immune cell populations expressing homeostatic and regulatory genes. Fourteen distinct clusters were identified, including myeloid cells (neutrophils, monocytes, macrophages), dendritic cells (DC), and lymphoid cells (B, T, γδT, ILC2, and NK) lineages. Novel neutrophil [lipocalin (Lcn2) high and low), and MHCIIlo macrophage (MP) clusters were identified. More than half of the cells map to myeloid and dendritic cell populations with differential expression profiles that include genes with homeostatic and regulatory functions: Serpinb2 (MHCIIlo macrophage), …

Risk Factors Associated With Patient-Reported Fatigue Among Long-Term Oropharyngeal Carcinoma Survivors, Puja Aggarwal, Katherine A Hutcheson, Ryan P Goepfert, Adam S Garden, Naveen Garg, Frank E Mott, Clifton D Fuller, Stephen Y Lai, Gary Brandon Gunn, Mark S Chambers, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors.

METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue.

RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and …

Identification Of An Optimal Dose Of Intravenous Ketamine For Late-Life Treatment-Resistant Depression: A Bayesian Adaptive Randomization Trial, Marijn Lijffijt, Nicholas Murphy, Sidra Iqbal, Charles E Green, Tabish Iqbal, Lee C Chang, Colin N Haile, Lorna C Hirsch, Nithya Ramakrishnan, Dylan A Fall, Alan C Swann, Rayan K Al Jurdi, Sanjay J Mathew

Faculty, Staff and Students Publications

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and …

Intestinal Deletion Of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion Of The Resident Stem Cell Compartment, Alexandria M Doerfler, Jun Han, Kelsey E Jarrett, Li Tang, Antrix Jain, Alexander Saltzman, Marco De Giorgi, Marcel Chuecos, Ayrea E Hurley, Ang Li, Pauline Morand, Claudia Ayala, David R Goodlett, Anna Malovannaya, James F Martin, Thomas Q De Aguiar Vallim, Noah Shroyer, William R Lagor

Faculty, Staff and Students Publications

BACKGROUND: The intestine occupies the critical interface between cholesterol absorption and excretion. Surprisingly little is known about the role of de novo cholesterol synthesis in this organ, and its relationship to whole body cholesterol homeostasis. Here, we investigate the physiological importance of this pathway through genetic deletion of the rate-limiting enzyme.

METHODS: Mice lacking 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) in intestinal villus and crypt epithelial cells were generated using a Villin-Cre transgene. Plasma lipids, intestinal morphology, mevalonate pathway metabolites, and gene expression were analyzed.

RESULTS: Mice with intestine-specific loss of Hmgcr were markedly smaller at birth, but gain …

Changes In Physical Activity Associated With The Covid-19 Pandemic In Individuals With Overweight And Obesity: An Interrupted Time Series Analysis With Historical Controls, Michael C Robertson, Che Young Lee, Ivan Haw-Chong Wu, Yue Liao, Margaret Raber, Nathan Parker, Thuan Le, Leticia Gatus, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The objective of this study was to investigate changes in physical activity patterns associated with the COVID-19 pandemic in individuals with overweight and obesity who were participating in a school district worksite weight loss program. We conducted comparative design interrupted time series analyses on physical activity device (Fitbit) data from the 2018-2019 and 2019-2020 school years (N = 211). We administered a questionnaire in 2020 to supplement device data. After the stay-at-home orders in 2020, participants tended to decrease their weekly step count (B = -1315.7, SE = 627.7, p = .045), decrease their weekly "Lightly active minutes" (B = …

Foxo1 Represses Sprouty 2 And Sprouty 4 Expression To Promote Arterial Specification And Vascular Remodeling In The Mouse Yolk Sac, Nanbing Li-Villarreal, Rebecca Lee Yean Wong, Monica D Garcia, Ryan S Udan, Ross A Poché, Tara L Rasmussen, Alexander M Rhyner, Joshua D Wythe, Mary E Dickinson

Faculty, Staff and Students Publications

Establishing a functional circulatory system is required for post-implantation development during murine embryogenesis. Previous studies in loss-of-function mouse models showed that FOXO1, a Forkhead family transcription factor, is required for yolk sac (YS) vascular remodeling and survival beyond embryonic day (E) 11. Here, we demonstrate that at E8.25, loss of Foxo1 in Tie2-cre expressing cells resulted in increased sprouty 2 (Spry2) and Spry4 expression, reduced arterial gene expression and reduced Kdr (also known as Vegfr2 and Flk1) transcripts without affecting overall endothelial cell identity, survival or proliferation. Using a Dll4-BAC-nlacZ reporter line, we found that one of the earliest expressed …

Targeting Calcium-Mediated Inter-Organellar Crosstalk In Cardiac Diseases, Mohit M Hulsurkar, Satadru K Lahiri, Jason Karch, Meng C Wang, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Abnormal calcium signaling between organelles such as the sarcoplasmic reticulum (SR), mitochondria and lysosomes is a key feature of heart diseases. Calcium serves as a secondary messenger mediating inter-organellar crosstalk, essential for maintaining the cardiomyocyte function.

AREAS COVERED: This article examines the available literature related to calcium channels and transporters involved in inter-organellar calcium signaling. The SR calcium-release channels ryanodine receptor type-2 (RyR2) and inositol 1,4,5-trisphosphate receptor (IP

EXPERT OPINION: Enhanced SR calcium release via RyR2 and reduced SR reuptake via SERCA2a, increased VDAC and MCUC-mediated calcium uptake into mitochondria, and enhanced lysosomal calcium-release via lysosomal TPC and TRPML …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Purpose, Subject, And Consumer Comment On "Perceived Burden Due To Registrations For Quality Monitoring And Improvement In Hospitals: A Mixed Methods Study", Sylvia J Hysong, Patrick O'Mahen, Jochen Profit, Laura A Petersen

Faculty, Staff and Students Publications

Zegers and colleagues’ study codifies the perceived burden of quality monitoring and improvement stemming from the work by clinicians of registering (documenting) quality information in the medical record. We agree with Zegers and colleagues’ recommendation that a smaller, more effective and curated set of measures is needed to reduce burden, confusion, and expense. We further note that focusing on validity of clinical evidence behind individual measures is critical, but insufficient. We therefore extend Zegers and colleagues’ work through a pragmatic, tripartite heuristic. To assess the value of and curate a targeted set of performance measures, we propose concentrating on the …

The Role Of Palmitoleic Acid In Regulating Hepatic Gluconeogenesis Through Sirt3 In Obese Mice, Xin Guo, Xiaofan Jiang, Keyun Chen, Qijian Liang, Shixiu Zhang, Juan Zheng, Xiaomin Ma, Hongmei Jiang, Hao Wu, Qiang Tong

Faculty, Staff and Students Publications

Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver’s response to nutrient deprivation, such as fatty …

Derivation And Validation Of A Novel Risk Assessment Tool To Identify Children Aged 2–59 Months At Risk Of Hospitalised Pneumonia-Related Mortality In 20 Countries, Chris A Rees, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Clare Cutland, Shabir Ahmed Madhi, Marta Nunes, Joseph L Matthew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash M Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Cissy B Kartasasmita, Marilla Lucero, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sudha Basnet, Tor A Strand, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Alexey W Clara, Harry Campbell, Harish Nair, Jennifer Falconer, Shamim A Qazi, Yasir B Nisar, Mark I Neuman, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings.

METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for …

Clinical Presentation, Treatment, And Genetic And Histopathological Analysis Of Juvenile Cataracts And Secondary Glaucoma In A Rhesus Macaque (Macaca Mulatta), M Isabel Casanova, Rui Chen, Laura M Garzel, Katherine J Olstad, Soohyun Kim, Ronald Alan Harris, Yumei Li, Muthuswamy Raveendran, Qingnan Liang, Jun Wang, Glenn Yiu, John Timothy Stout, Jeffrey A Roberts, Jeffrey Rogers, Ala Moshiri, Sara M Thomasy

Faculty, Staff and Students Publications

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

Colonic Epithelial Angiotensin-Converting Enzyme 2 (Ace2) Expression In Blacks And Whites: Potential Implications For Pathogenesis Covid-19 Racial Disparities, Mart De La Cruz, David P Nunes, Vaishali Bhardwaj, Deepika Subramanyan, Caroline Zaworski, Priya Roy, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites.

METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent …

Cell Type-Specific Roles Of Stat3 Signaling In The Pathogenesis And Progression Of K-Ras Mutant Lung Adenocarcinoma, Michael J Clowers, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Worldwide, lung cancer, particularly K-ras mutant lung adenocarcinoma (KM-LUAD), is the leading cause of cancer mortality because of its high incidence and low cure rate. To treat and prevent KM-LUAD, there is an urgent unmet need for alternative strategies targeting downstream effectors of K-ras and/or its cooperating pathways. Tumor-promoting inflammation, an enabling hallmark of cancer, strongly participates in the development and progression of KM-LUAD. However, our knowledge of the dynamic inflammatory mechanisms, immunomodulatory pathways, and cell-specific molecular signals mediating K-ras-induced lung tumorigenesis is substantially deficient. Nevertheless, within this signaling complexity, an inflammatory pathway is emerging as a druggable target: signal …

Cistrome And Transcriptome Analysis Identifies Unique Androgen Receptor (Ar) And Ar-V7 Splice Variant Chromatin Binding And Transcriptional Activities, Paul Basil, Matthew J Robertson, William E Bingman, Amit K Dash, William C Krause, Ayesha A Shafi, Badrajee Piyarathna, Cristian Coarfa, Nancy L Weigel

Faculty, Staff and Students Publications

The constitutively active androgen receptor (AR) splice variant, AR-V7, plays an important role in resistance to androgen deprivation therapy in castration resistant prostate cancer (CRPC). Studies seeking to determine whether AR-V7 is a partial mimic of the AR, or also has unique activities, and whether the AR-V7 cistrome contains unique binding sites have yielded conflicting results. One limitation in many studies has been the low level of AR variant compared to AR. Here, LNCaP and VCaP cell lines in which AR-V7 expression can be induced to match the level of AR, were used to compare the activities of AR and …

Prmt7 Ablation Stimulates Anti-Tumor Immunity And Sensitizes Melanoma To Immune Checkpoint Blockade, Nivine Srour, Oscar D Villarreal, Swanand Hardikar, Zhenbao Yu, Samuel Preston, Wilson H Miller, Magdelena M Szewczyk, Dalia Barsyte-Lovejoy, Han Xu, Taiping Chen, Sonia V Del Rincón, Stéphane Richard

Faculty, Staff and Student Publications

Despite the success of immune checkpoint inhibitor (ICI) therapy for cancer, resistance and relapse are frequent. Combination therapies are expected to enhance response rates and overcome this resistance. Herein, we report that combining PRMT7 inhibition with ICI therapy induces a strong anti-tumor T cell immunity and restrains tumor growth in vivo by increasing immune cell infiltration. PRMT7-deficient B16.F10 melanoma exhibits increased expression of genes in the interferon pathway, antigen presentation, and chemokine signaling. PRMT7 deficiency or inhibition with SGC3027 in B16.F10 melanoma results in reduced DNMT expression, loss of DNA methylation in the regulatory regions of endogenous retroviral elements (ERVs) …

Oleic Acid Is An Endogenous Ligand Of Tlx/Nr2e1 That Triggers Hippocampal Neurogenesis, Prasanna Kandel, Fatih Semerci, Rachana Mishra, William Choi, Aleksandar Bajic, Dodge Baluya, Lihua Ma, Kevin Chen, Austin C Cao, Tipwarin Phongmekhin, Nick Matinyan, Alba Jiménez-Panizo, Srinivas Chamakuri, Idris O Raji, Lyra Chang, Pablo Fuentes-Prior, Kevin R Mackenzie, Caroline L Benn, Eva Estébanez-Perpiñá, Koen Venken, David D Moore, Damian W Young, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated …

Adolescents Accessing School-Based Versus Family Planning Clinics: Chlamydia And Gonorrhea Testing And Treatment Outcomes, Meghna Raphael, Allyssa A Abacan, Peggy B Smith, Mariam R Chacko

Faculty, Staff and Students Publications

The prevalence and treatment of chlamydia (CT) and gonorrhea (GC) at school-based clinics (SBCs) requires revisiting. To assess whether clinic type influences CT/GC testing and treatment for minors (individuals 13–17 years of age), our study compared four SBCs with five family planning clinics (FPCs) in the Houston, Harris County metropolitan area of Texas, USA for: (1) the prevalence of CT/GC infection (pre-COVID-19 and during COVID-19); (2) treatment rates at the last positive diagnosis; and (3) the time, in days, from testing-to-diagnosis and testing-to-treatment. Between January 2019 and December 2020, 2439 unique patients (1579 at SBCs, 860 at FPCs) were seen. …

Wwox Binding To The Murine Brca1-Brct Domain Regulates Timing Of Brip1 And Ctip Phospho-Protein Interactions With This Domain At Dna Double-Strand Breaks, And Repair Pathway Choice, Dongju Park, Mehdi Gharghabi, Colleen R Reczek, Rebecca Plow, Charles Yungvirt, C Marcelo Aldaz, Kay Huebner

Faculty, Staff and Student Publications

Wwox-deficient human cells show elevated homologous recombination, leading to resistance to killing by double-strand break-inducing agents. Human Wwox binds to the Brca1 981-PPLF-984 Wwox-binding motif, likely blocking the pChk2 phosphorylation site at Brca1-S988. This phosphorylation site is conserved across mammalian species; the PPLF motif is conserved in primates but not in rodents. We now show that murine Wwox does not bind Brca1 near the conserved mouse Brca1 phospho-S971 site, leaving it open for Chk2 phosphorylation and Brca1 activation. Instead, murine Wwox binds to Brca1 through its BRCT domain, where pAbraxas, pBrip1, and pCtIP, of the A, B, and C binding …

Anti-Tumor Activity Of Cetuximab Plus Avelumab In Non-Small Cell Lung Cancer Patients Involves Innate Immunity Activation: Findings From The Cave-Lung Trial, Carminia Maria Della Corte, Morena Fasano, Vincenza Ciaramella, Flora Cimmino, Robert Cardnell, Carl M Gay, Kavya Ramkumar, Lixia Diao, Raimondo Di Liello, Giuseppe Viscardi, Vincenzo Famiglietti, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Concetta Tuccillo, Teresa Troiani, Erika Martinelli, Jing Wang, Lauren Byers, Floriana Morgillo, Fortunato Ciardiello

Faculty, Staff and Student Publications

BACKGROUND: We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC). Among the 6 responding patients, 3 had progressed after initial response to a previous treatment with single agent anti-PD-1, nivolumab or pembrolizumab.

METHODS: We report long-term clinical follow-up and additional …

Newborn Screening: Review Of Its Impact For Cystinosis, Katharina Hohenfellner, Ewa Elenberg, Gema Ariceta, Galina Nesterova, Neveen A Soliman, Rezan Topaloglu

Faculty, Staff and Students Publications

Newborn screening (NBS) programmes are considered to be one of the most successful secondary prevention measures in childhood to prevent or reduce morbidity and/or mortality via early disease identification and subsequent initiation of therapy. However, while many rare diseases can now be detected at an early stage using appropriate diagnostics, the introduction of a new target disease requires a detailed analysis of the entire screening process, including a robust scientific background, analytics, information technology, and logistics. In addition, ethics, financing, and the required medical measures need to be considered to allow the benefits of screening to be evaluated at a …

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation For B-Lineage Acute Lymphoblastic Leukemia, Mahmoud R Gaballa, Pinaki Banerjee, Denái R Milton, Xianli Jiang, Christina Ganesh, Sajad Khazal, Vandana Nandivada, Sanjida Islam, Mecit Kaplan, May Daher, Rafet Basar, Amin Alousi, Rohtesh Mehta, Gheath Alatrash, Issa Khouri, Betul Oran, David Marin, Uday Popat, Amanda Olson, Priti Tewari, Nitin Jain, Elias Jabbour, Farhad Ravandi, Hagop Kantarjian, Ken Chen, Richard Champlin, Elizabeth Shpall, Katayoun Rezvani, Partow Kebriaei

Faculty, Staff and Student Publications

Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the …

Temperature Changes During Implant Osteotomy Preparations In Fresh Human Cadaver Tibiae, Comparing Straight With Tapered Drills, Nikolaos Soldatos, Laura Nelson-Rabe, Nathan Palanker, Nikola Angelov, Georgios Romanos, Robin Weltman

Faculty, Staff and Student Publications

The success of osseointegration depends on many factors. With temperatures beyond a 47 °C threshold over 1 min, bone survival may be impaired. The purpose of the study was to evaluate, in fresh human cadaver tibiae, the temperature changes during osteotomy preparations using two straight and two tapered implant systems' drills, external irrigation, and varying revolutions per minute (RPM). The tibiae from a fresh female cadaver were harvested bilaterally. Two tapered and two straight design drills were assessed. Two-hundred and forty osteotomies were prepared at 6 mm depth following the drill sequence of the manufacturers' protocol for each drilling speed. …

Micrornas In Leukemias: A Clinically Annotated Compendium, Aleksander Turk, George A Calin, Tanja Kunej

Faculty, Staff and Student Publications

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved …

Targeted Dual-Modal Pet/Spect-Nir Imaging: From Building Blocks And Construction Strategies To Applications, Syed Muhammad Usama, Sierra C Marker, Servando Hernandez Vargas, Solmaz Aghaamiri, Sukhen C Ghosh, Naruhiko Ikoma, Hop S Tran Cao, Martin J Schnermann, Ali Azhdarinia

Faculty, Staff and Student Publications

Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal …

Ms 044 Guide To H. Grant Taylor, Md Papers (1925-1992), H. Grant Taylor (1903-1995)

Manuscript Finding Aids

Papers consist primarily of personal and professional correspondence; board meeting and committee meeting minutes and reports; drafts, manuscripts, and published professional papers; documentation chronicling his role with the Atomic Bomb Casualty Commission (ABCC) in Japan, his role in the organization and development of a regional medical plan centered in Houston, of the University of Texas (UT) Postgraduate School of Medicine and its Division of Continuing Education, and of M. D. Anderson Hospital and Tumor Institute (MDAH), currently known as UT M. D. Anderson Cancer Center, and its renowned Department of Pediatrics. See more at MS 044.

Ms 064 Guide To Robert D. Lange, Md Papers (1954-1966), Robert D. Lange (1920-1999)

Manuscript Finding Aids

The Robert D. Lange Collection contains publications and reprints from the Atomic Bomb Casualty Commission, The Journal of the Hiroshima Medical Association, Blood, The Journal of Hematology, Texas Reports on Biology and Medicine. Unique to this collection are the 46 lantern slides. The contribution consists of lantern slides, publications and a set of 35 mm slides. The print and photographic materials in this small collection complement each other well. See more at MS 064.

Fusionai, A Dna-Sequence-Based Deep Learning Protocol Reduces The False Positives Of Human Fusion Gene Prediction, Pora Kim, Hua Tan, Jiajia Liu, Himansu Kumar, Xiaobo Zhou

Faculty, Staff and Student Publications

Even though there were many tool developments of fusion gene prediction from NGS data, too many false positives are still an issue. Wise use of the genomic features around the fusion gene breakpoints will be helpful to identify reliable fusion genes efficiently. For this aim, we developed FusionAI, a deep learning pipeline predicting human fusion gene breakpoints from DNA sequence. FusionAI is freely available via https://compbio.uth.edu/FusionGDB2/FusionAI. For complete details on the use and execution of this protocol, please refer to Kim et al. (2021b).