Digital Commons Network^™

Prioritization Of Risk Genes In Multiple Sclerosis By A Refined Bayesian Framework Followed By Tissue-Specificity And Cell Type Feature Assessment, Andi Liu, Astrid M Manuel, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Multiple sclerosis (MS) is a debilitating immune-mediated disease of the central nervous system that affects over 2 million people worldwide, resulting in a heavy burden to families and entire communities. Understanding the genetic basis underlying MS could help decipher the pathogenesis and shed light on MS treatment. We refined a recently developed Bayesian framework, Integrative Risk Gene Selector (iRIGS), to prioritize risk genes associated with MS by integrating the summary statistics from the largest GWAS to date (n = 115,803), various genomic features, and gene-gene closeness.

RESULTS: We identified 163 MS-associated prioritized risk genes (MS-PRGenes) through the Bayesian framework. …

Lncrnas Uc145 And Prkg1-As1 Determine The Functional Output Of Dkk1 In Regulating The Wnt Signaling Pathway In Gastric Cancer, Jung-Ho Yoon, Hyojoo Byun, Cristina Ivan, George A Calin, Dahyun Jung, Sangkil Lee

Faculty, Staff and Student Publications

DKK1 inhibits the canonical Wnt signaling pathway that is known to be involved in various cancers. However, whether DKK1 acts as an oncogene or tumor suppressor gene remains controversial. Furthermore, the DKK1-regulating mechanism in gastric cancer has not yet been defined. The aim of this study was to explore whether the ultraconserved region UC.145 regulates epigenetic changes in DKK1 expression in gastric cancer. Microarray analysis revealed that UC.145 exhibited the highest binding affinity to EZH2, a histone methyltransferase. The effects of UC.145 inactivation were assessed in gastric cancer cell lines using siRNA. The results indicated that UC.145 triggers DKK1 methylation …

Immunogenomic Intertumor Heterogeneity Across Primary And Metastatic Sites In A Patient With Lung Adenocarcinoma, Runzhe Chen, Jun Li, Junya Fujimoto, Lingzhi Hong, Xin Hu, Kelly Quek, Ming Tang, Akash Mitra, Carmen Behrens, Chi-Wan Chow, Peixin Jiang, Latasha D Little, Curtis Gumbs, Xingzhi Song, Jianhua Zhang, Dongfeng Tan, John V Heymach, Ignacio Wistuba, P Andrew Futreal, Don L Gibbons, Lauren A Byers, Jianjun Zhang, Alexandre Reuben

Faculty, Staff and Student Publications

Background: Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.

Methods: In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a 32-year-old female never-smoker with left lung primary late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors. …

The Technical Landscape For Patient-Centered Cds: Progress, Gaps, And Challenges, Prashila Dullabh, Krysta Heaney-Huls, David F Lobach, Lauren S Hovey, Shana F Sandberg, Priyanka J Desai, Edwin Lomotan, James Swiger, Michael I Harrison, Chris Dymek, Dean F Sittig, Aziz Boxwala

Faculty, Staff and Student Publications

Supporting healthcare decision-making that is patient-centered and evidence-based requires investments in the development of tools and techniques for dissemination of patient-centered outcomes research findings via methods such as clinical decision support (CDS). This article explores the technical landscape for patient-centered CDS (PC CDS) and the gaps in making PC CDS more shareable, standards-based, and publicly available, with the goal of improving patient care and clinical outcomes. This landscape assessment used: (1) a technical expert panel; (2) a literature review; and (3) interviews with 18 CDS stakeholders. We identified 7 salient technical considerations that span 5 phases of PC CDS development. …

Asthma And Technology In Emerging African American Adults (The Athena Project): Protocol For A Trial Using The Multiphase Optimization Strategy Framework, Alan Baptist, Wanda Gibson-Scipio, April Idalski Carcone, Samiran Ghosh, Angela J Jacques-Tiura, Amy Hall, Karen Kolmodin Macdonell

Faculty, Staff and Student Publications

BACKGROUND: Asthma causes substantial morbidity and mortality in the United States, particularly among African American emerging adults (AAEAs; aged 18-30 years), but very few asthma programs have targeted this population. Interventions that provide education and address underlying motivation for managing asthma may be the most effective. However, intensive face-to-face interventions are often difficult to implement in this population.

OBJECTIVE: The purpose of this study is to develop an effective mobile asthma management intervention to improve control among AAEAs.

METHODS: We will assess the ability of multiple technologic components to assist and improve traditional asthma education. The first component is the …

Racial And Ethnic Differences In Genomic Profiling Of Early Onset Colorectal Cancer, David M Hein, Weiye Deng, Marylena Bleile, Syed Ali Kazmi, Brooke Rhead, Francisco M De La Vega, Amy L Jones, Radhika Kainthla, Wen Jiang, Brandi Cantarel, Nina N Sanford

Faculty, Staff and Student Publications

The incidence and mortality of early onset colorectal cancer (EOCRC) is rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, White Hispanic) using data from the American Association for Cancer Research Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1752 EOCRC patients, non-Hispanic Black patients had higher rates of KRAS mutations (60.9%; P = .001, q = 0.015), and non-Hispanic White and non-Hispanic Black …

Pattern Differentiation And Tuning Shift In Human Sensory Cortex Underlie Long-Term Threat Memory, Yuqi You, Lucas R Novak, Kevin J Clancy, Wen Li

Faculty, Staff and Student Publications

The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system 1, but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit 2-4. Through non-human research, the sensory cortex has emerged as a critical substrate for long-term threat memory 5-9, underpinned by sensory cortical pattern separation/completion 10,11 and tuning shift 12,13. In humans, research has begun to associate the human sensory cortex with long-term threat memory 14,15, but the lack of mechanistic insights obscures a direct linkage. Towards that end, …

Polygenic Transcriptome Risk Scores For Copd And Lung Function Improve Cross-Ethnic Portability Of Prediction In The Nhlbi Topmed Program, Xiaowei Hu, Dandi Qiao, Wonji Kim, Matthew Moll, Pallavi P Balte, Leslie A Lange, Traci M Bartz, Rajesh Kumar, Xingnan Li, Bing Yu, Brian E Cade, Cecelia A Laurie, Tamar Sofer, Ingo Ruczinski, Deborah A Nickerson, Donna M Muzny, Ginger A Metcalf, Harshavardhan Doddapaneni, Stacy Gabriel, Namrata Gupta, Shannon Dugan-Perez, L Adrienne Cupples, Laura R Loehr, Deepti Jain, Jerome I Rotter, James G Wilson, Bruce M Psaty, Myriam Fornage, Alanna C Morrison, Ramachandran S Vasan, George Washko, Stephen S Rich, George T O'Connor, Eugene Bleecker, Robert C Kaplan, Ravi Kalhan, Susan Redline, Sina A Gharib, Deborah Meyers, Victor Ortega, Josée Dupuis, Stephanie J London, Tuuli Lappalainen, Elizabeth C Oelsner, Edwin K Silverman, R Graham Barr, Timothy A Thornton, Heather E Wheeler, Topmed Lung Working Group, Michael H Cho, Hae Kyung Im, Ani Manichaikul

Faculty, Staff and Student Publications

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and …

A Bayesian Group Sequential Design For Randomized Biosimilar Clinical Trials With Adaptive Information Borrowing From Historical Data, Wen Zhang, Zhiying Pan, Ying Yuan

Faculty, Staff and Student Publications

At the time of developing a biosimilar, the reference product has been on market for years and thus ample data are available on its efficacy and characteristics. We develop a Bayesian adaptive design for randomized biosimilar clinical trials to leverage the rich historical data on the reference product. This design takes a group sequential approach. At each interim, we employ the elastic meta-analytic-predictive (EMAP) prior methodology to adaptively borrow information from the historical data of the reference product to make go/no-go decision based on Bayesian posterior probabilities. In addition, the randomization ratio between the test and reference arms is adaptively …

Iv Sotalol Use In Pediatric And Congenital Heart Patients: A Multicenter Registry Study, Lindsey E Malloy-Walton, Nicholas H Von Bergen, Seshadri Balaji, Peter S Fischbach, Jason M Garnreiter, S Yukiko Asaki, Jeffrey P Moak, Luis A Ochoa, Philip M Chang, Hoang H Nguyen, Akash R Patel, Christa Kirk, Ashley K Sherman, Jennifer N Avari Silva, J Philip Saul

Faculty, Staff and Student Publications

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. …

A Community-Led Mobile Health Clinic To Improve Structural And Social Determinants Of Health Among (Im)Migrant Workers, Shannon Guillot-Wright, N Miles Farr, Ellie Cherryhomes

Faculty, Staff and Student Publications

BACKGROUND: Community-led interventions that address structural and social determinants of health are lacking among (im)migrant workers, especially seafood workers. This lack of medical attention is especially alarming given their high rate of injury and death.

METHODS: Community-based participatory research (CBPR), a relational model that values the participants as equal partners in research, dissemination, and implementation, guided the interviews and mobile clinic. Seafood workers were engaged throughout data collection, analysis, and interpretation and played a significant role in moving the findings from research into actionable change.

RESULTS: to address the lack of healthcare options for (im)migrants, and at the request of …

Hypomethylating Agent And Venetoclax With Flt3 Inhibitor “Triplet” Therapy In Older/Unfit Patients With Flt3 Mutated Aml, Musa Yilmaz, Hagop Kantarjian, Nicholas J Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver

Faculty, Staff and Student Publications

In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a …

The Genomic Alterations In Glioblastoma Influence The Levels Of Csf Metabolites, Wilfredo De Jesús-Rojas, José Muñiz-Hernández, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, Arnaldo J Santos-López, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) has been linked to more than 50 genes that cause a spectrum of clinical symptoms, including newborn respiratory distress, sinopulmonary infections, and laterality abnormalities. Although the RSPH4A (c.921+3_6delAAGT) pathogenic variant has been related to Hispanic groups with Puerto Rican ancestry, it is uncertain how frequently other PCD-implicated genes are present on the island. A retrospective chart review of n = 127 genetic reports from Puerto Rican subjects who underwent genetic screening for PCD variants was conducted from 2018 to 2022. Of 127 subjects, 29.1% subjects presented PCD pathogenic variants, and 13.4% were homozygous for the RSPH4A …

Novel And Extendable Genotyping System For Human Respiratory Syncytial Virus Based On Whole-Genome Sequence Analysis, Jiani Chen, Xueting Qiu, Vasanthi Avadhanula, Samuel S Shepard, Do-Kyun Kim, James Hixson, Pedro A Piedra, Justin Bahl

Faculty, Staff and Student Publications

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition.

METHODS: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair-wise node distances.

RESULTS: …

Differential Ets1 Binding To T:G Mismatches Within A Cpg Dinucleotide Contributes To C-To-T Somatic Mutation Rate Of The Idh2 Hotspot At Codon Arg140, Jie Yang, Esha Gupta, John R Horton, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Cytosine to thymine (C>T) somatic mutation is highly enriched in certain types of cancer, and most commonly occurs via deamination of a 5-methylcytosine (5mC) to thymine, in the context of a CpG dinucleotide. In theory, deamination should occur at equal rates to both 5mC nucleotides on opposite strands. In most cases, the resulting T:G or G:T mismatch can be repaired by thymine DNA glycosylase activities. However, while some hotspot-associated CpG mutations have approximately equal numbers of mutations that resulted either from C>T or G>A in a CpG dinucleotide, many showed strand bias, being skewed toward C>T …

Barriers And Facilitators Of Implementing Automated Radiotherapy Planning: A Multisite Survey Of Low- And Middle-Income Country Radiation Oncology Providers, Gwendolyn J Mcginnis, Matthew S Ning, Beth M Beadle, Nanette Joubert, William Shaw, Christoph Trauernich, Hannah Simonds, Surbhi Grover, Carlos E Cardenas, Laurence E Court, Grace L Smith

Faculty, Staff and Student Publications

Purpose: Global access to radiotherapy (RT) is inequitable, with obstacles to implementing modern technologies in low- and middle- income countries (LMICs). The Radiation Planning Assistant (RPA) is a web-based automated RT planning software package intended to increase accessibility of high-quality RT planning. We surveyed LMIC RT providers to identify barriers and facilitators of future RPA deployment and uptake.

Methods: RT providers underwent a pilot RPA teaching session in sub-Saharan Africa (Botswana, South Africa, and Tanzania) and Central America (Guatemala). Thirty providers (30 of 33, 90.9% response rate) participated in a postsession survey.

Results: Respondents included physicians (n = 10, 33%), …

Venetoclax Combined With Induction Chemotherapy In Patients With Newly Diagnosed Acute Myeloid Leukaemia: A Post-Hoc, Propensity Score-Matched, Cohort Study, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Sanam Loghavi, Ken Furudate, Lianchun Xiao, Sherry Pierce, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Marina Konopleva, Naveen Pemmaraju, Uday Popat, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Courtney D Dinardo, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Venetoclax combined with intensive chemotherapy has been shown to be safe with promising activity in fit patients with newly diagnosed acute myeloid leukaemia. The aim of this study was to compare the activity of venetoclax plus intensive chemotherapy with intensive chemotherapy alone.

Methods: This was a post-hoc propensity score matched analysis of prospective clinical trials (NCT03214562, NCT02115295, and NCT01289457) in patients at The University of Texas MD Anderson Cancer Center, Texas, USA between March 29, 2010, and June 15, 2021. Eligible patients were aged 18 years and older, and had newly diagnosed acute myeloid leukaemia …

Activity Of Decitabine As Maintenance Therapy In Core Binding Factor Acute Myeloid Leukemia, Jayastu Senapati, Mahran Shoukier, Guillermo Garcia-Manero, Xuemei Wang, Keyur Patel, Tapan Kadia, Farhad Ravandi, Naveen Pemmaraju, Maro Ohanian, Naval Daver, Courtney Dinardo, Yesid Alvarado, Jeffrey Aldrich, Gautam Borthakur

Faculty, Staff and Student Publications

Background: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML.

Methods: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)-based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%.

Results: Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received …

New Practical Aspects Of Sweet Syndrome, Tejas P Joshi, Sarah K Friske, David A Hsiou, Madeleine Duvic

Faculty, Staff and Student Publications

Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous papules/plaques/pustules/nodules commonly appearing on the upper limbs, trunk, and head and neck; histologically, SS is characterized by dense neutrophilic infiltrate in the dermis. SS is accompanied by fever; an elevation of inflammatory markers (e.g., erythrocyte sedimentation rate, C reactive protein) in serum may also be observed. Although most cases of SS are idiopathic, SS also occurs in the setting of malignancy or following administration of an associated drug. SS has also been reported in association with pregnancy and a burgeoning list …

Home Cooking Quality Assessment Tool Validation Using Community Science And Crowdsourcing Approaches, Margaret Raber, Nalini Ranjit, Larkin L Strong, Karen Basen-Engquist

Faculty, Staff and Student Publications

Objective: To refine a measure of home cooking quality (defined as the usage level of practices with the potential to influence the nutrient content of prepared foods) and conduct a construct validation of the revised tool, the Healthy Cooking Questionnaire 2 (HCQ2).

Design: Two validation approaches are described: (1) a community science approach used to refine and validate Healthy Cooking Questionnaire (HCQ) constructs, and (2) responses to the revised HCQ (HCQ2) in a sample of Amazon Mechanical Turk (MTurk) workers to determine questionnaire comprehension.

Setting: The Community Scientist Program at the University of Texas MD Anderson Cancer Center facilitated discussion …

Home Cooking Quality Assessment Tool Validation Using Community Science And Crowdsourcing Approaches, Margaret Raber, Nalini Ranjit, Larkin L Strong, Karen Basen-Engquist

Faculty, Staff and Student Publications

Objective: To refine a measure of home cooking quality (defined as the usage level of practices with the potential to influence the nutrient content of prepared foods) and conduct a construct validation of the revised tool, the Healthy Cooking Questionnaire 2 (HCQ2).

Design: Two validation approaches are described: (1) a community science approach used to refine and validate Healthy Cooking Questionnaire (HCQ) constructs, and (2) responses to the revised HCQ (HCQ2) in a sample of Amazon Mechanical Turk (MTurk) workers to determine questionnaire comprehension.

Setting: The Community Scientist Program at the University of Texas MD Anderson Cancer Center facilitated discussion …

Building Capacity For Cancer Research In The Era Of Covid-19: Implementation And Results From An International Virtual Clinical Research Training Program In Zambia, Kevin Diao, Dorothy C Lombe, Catherine K Mwaba, Juliana Wu, Darya A Kizub, Carrie A Cameron, Elizabeth Y Chiao, Susan C Msadabwe, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: The incidence of cancer in sub-Saharan Africa is increasing rapidly, yet cancer research in the region continues to lag. One contributing factor is limited exposure to clinical research among trainees. We describe implementation and results of a virtual clinical research training program for Zambian clinical oncology fellows developed jointly by the Cancer Diseases Hospital in Zambia and the MD Anderson Cancer Center to address this need.

Methods: The clinical research training program consisted of 14 weekly virtual lectures, development of research questions by Zambian clinical oncology fellows, assignment of faculty and peer mentors, longitudinal mentorship of research protocols, and …

Chromatin State Dynamics Confers Specific Therapeutic Strategies In Enhancer Subtypes Of Colorectal Cancer, Elias Orouji, Ayush T Raman, Anand K Singh, Alexey Sorokin, Emre Arslan, Archit K Ghosh, Jonathan Schulz, Christopher Terranova, Shan Jiang, Ming Tang, Mayinuer Maitituoheti, Scot C Callahan, Praveen Barrodia, Katarzyna Tomczak, Yingda Jiang, Zhiqin Jiang, Jennifer S Davis, Sukhen Ghosh, Hey Min Lee, Laura Reyes-Uribe, Kyle Chang, Yusha Liu, Huiqin Chen, Ali Azhdarinia, Jeffrey Morris, Eduardo Vilar, Kendra S Carmon, Scott E Kopetz, Kunal Rai

Faculty, Staff and Student Publications

Objective: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.

Design: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and …

Whole Exome Sequencing Identifies Potential Candidate Genes For Spina Bifida Derived From Mouse Models, Chunyan Wang, Steve Seltzsam, Bixia Zheng, Chen-Han Wilfred Wu, Camille Nicolas-Frank, Kirollos Yousef, Kit Sing Au, Nina Mann, Dalia Pantel, Sophia Schneider, Luca Schierbaum, Thomas M Kitzler, Dervla M Connaughton, Youying Mao, Rufeng Dai, Makiko Nakayama, Jameela A Kari, Sherif El Desoky, Mohammed Shalaby, Loai A Eid, Hazem S Awad, Velibor Tasic, Shrikant M Mane, Richard P Lifton, Michelle A Baum, Shirlee Shril, Carlos R Estrada, Friedhelm Hildebrandt

Faculty, Staff and Student Publications

Spina bifida (SB) is the second most common nonlethal congenital malformation. The existence of monogenic SB mouse models and human monogenic syndromes with SB features indicate that human SB may be caused by monogenic genes. We hypothesized that whole exome sequencing (WES) allows identification of potential candidate genes by (i) generating a list of 136 candidate genes for SB, and (ii) by unbiased exome-wide analysis. We generated a list of 136 potential candidate genes from three categories and evaluated WES data of 50 unrelated SB cases for likely deleterious variants in 136 potential candidate genes, and for potential SB candidate …

An Evaluation Of Seasonal Maternal-Neonatal Morbidity Related To Trainee Cycles, Ayamo Oben, Paula Mcgee, William A Grobman, Jennifer L Bailit, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Mona Prasad, George R Saade, Dwight J Rouse, Sean C Blackwell, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

BACKGROUND:

The existence of the “July phenomenon” (worse outcomes related to the presence of new physician trainees in teaching hospitals) has been debated in the literature and media. Previous studies of the phenomenon in obstetrics are limited by the quality and detail of data.

OBJECTIVE:

To evaluate whether the months of June to August, when transitions in trainees occur, are associated with increased maternal and neonatal morbidity.

STUDY DESIGN:

Secondary analysis of an observational cohort of 115,502 mother–infant pairs that delivered at 25 hospitals from March 2008 to February 2011. Inclusion criteria were an individual who had a singleton, nonanomalous …

Predictive Performance Of Newborn Small For Gestational Age By A Us Intrauterine Versus Birth Weight-Derived Standard For Short-Term Neonatal Morbidity And Mortality, Nathan R Blue, Lisa Mele, William A Grobman, Jennifer L Bailit, Ronald J Wapner, John M Thorp, Steve N Caritis, Mona Prasad, Alan T N Tita, George R Saade, Dwight J Rouse, Sean C Blackwell, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

Objective:

The use of birth weight standards to define small for gestational age (SGA) may fail to identify neonates affected by poor fetal growth since they include births associated with sub-optimal fetal growth. Our objective was to compare intrauterine versus birth weight-derived standards to define newborn SGA to predict neonatal morbidity and mortality.

Study Design:

This was a secondary analysis of a multi-center observational study of 118,422 births. Liveborn singleton, non-anomalous newborns born at 23–41 weeks were included. Those with missing gestational age estimation or without a 1^st or 2^nd trimester ultrasound to confirm dating, birth weight, or …

Hemophilia A: Strategies For Improving Long-Term Holistic Management, Adherence, And Quality Of Life, Miguel A Escobar, Cindy Leissinger, Guy Young

Faculty, Staff and Student Publications

Hemophilia A is a rare inherited bleeding disorder characterized by a deficiency in factor VIII. The evolution of currently approved prophylaxis therapy in hemophilia A will be reviewed, including the clinical value of prophylaxis, real-world experience with prophylaxis, and patient quality-of-life factors that must be considered when choosing treatment options for these patients.

Perifollicular Hypopigmentation In Systemic Sclerosis: Associations With Clinical Features And Internal Organ Involvement, Melody P Chung, Christopher A Mecoli, Jamie Perin, Carrie Richardson, Zsuzsanna H Mcmahan

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether perifollicular hypopigmentation in systemic sclerosis (SSc) is associated with demographics, distinct clinical features, and autoantibody profiles.

METHODS: Patients with SSc were prospectively enrolled, with a standardized data form used to collect anatomic distribution of perifollicular hypopigmentation. Associations between hypopigmentation and features of SSc were assessed.

RESULTS: Of 179 adult patients with SSc, 36 (20%) patients had perifollicular hypopigmentation. Of these 36 patients, 94% (n = 34) were female and 33% (n = 12) had limited cutaneous SSc. In univariable logistic regression, Black race (odds ratio [OR] 15.63, 95% CI 6.6-37.20,

CONCLUSION: Perifollicular hypopigmentation is observed in …

Src Stimulates Abl-Dependent Phosphorylation Of The Guanine Exchange Factor Net1a To Promote Its Cytosolic Localization And Cell Motility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh

Faculty, Staff and Student Publications

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), …

Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel

Faculty, Staff and Student Publications

NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3' UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture …