Medical Specialties Commons^™

The Impact Of Cumulative And Acute Loading On Achilles Tendon Health, Performance, And Reported Pain In Collegiate Gymnasts, Julio Serrano Samayoa

Electronic Theses and Dissertations

Gymnasts are at a high risk of Achilles tendon (AT) injuries due to intense loads during takeoffs and landings. To better understand better the relationship between impact loading and its effects on tendon adaptation and athletic performance, this study uses Inertial Measurement Units (IMUs) to track AT loading across a collegiate gymnastics season. This data were compared against physiological and athletic performance metrics, obtained through force plates and ultrasound imaging, to explore how mechanical load influences reported pain and athletic performance. Results varied, with cumulative impacts being correlated with improved jump height (Spearman 0.362, Pearson 0.348), while peak power and …

Applications Of Computer Vision In Biomechanics And Orthopaedics, William Stewart Burton Ii

Electronic Theses and Dissertations

Machine learning has emerged as a key technology for enabling advanced computer vision systems. These systems now permeate many industries, and have enhanced traditional processes through autonomous interpretation of visual data. In the field of orthopaedics, the increasing prevalence of imaging highlights a need for similar tools. In many cases, however, direct translation of available frameworks fails to resolve the complex problems currently facing this field. Stringent performance requirements, complex visual environments, data scarcity, and implications for patient safety represent domain-specific factors which pose unique challenges to proven techniques. Novel approaches are needed to realize the full benefits of visual …

Editorial: Cardiogenic Shock: Basic And Clinical Consideration, Volume Ii, Umberto Di Dedda, Indranee Rajapreyar, J. Eduardo Rame, Clement Delmas, Paolo Meani

Division of Cardiology Faculty Papers

No abstract provided.

Identification Of Lrp1+Cd13+ Human Periosteal Stem Cells That Require Lrp1 For Bone Repair, Youngjae Jeong, Lorenzo Deveza, Laura Ortinau, Kevin Lei, John R Dawson, Dongsu Park

Faculty, Staff and Students Publications

Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, podoplanin (PDPN) and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs, selectively expressed identified markers low density lipoprotein receptor-related protein 1 (LRP1) and CD13. These LRP1+CD13+ human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. Upon transplantation into bone injuries in mice, they preserved self-renewal capability in vivo. Single-cell analysis of mouse periosteum further supported the preferential …

Improving Healthcare Utilization Models And Uncovering Health Behavior Patterns In Asian Americans Through Data Disaggregation, Luke Cho

Undergraduate Research Symposium Podium Presentations

Although Asian Americans are made up of 20+ distinct ethnicities with unique health outcomes, previous healthcare research has treated them as a monolithic group, covering up many important disparities in health outcomes and healthcare utilization patterns. This study examines how disaggregating Asian American health data by ethnicity improves models analyzing healthcare utilization patterns, focusing on routine physicals, dental checkups, alternative medicine consultations, and preference for ethnic concordance.

Using data from the 2015 Asian American Quality of Life survey (2,609 adults in Austin, Texas), binomial generalized linear models (GLMs) analyzed the impact of income, age, gender, insurance status, and ethnicity on …

Maternal Morbidity Associated With Early Preterm Birth In Low-Risk Singleton Pregnancies, Moti Gulersen, Erez Lenchner, Alisha Goyal, Amos Grunebaum, Frank A. Chervenak, Eran Bornstein

Department of Obstetrics and Gynecology Faculty Papers

Background/Objectives: While neonatal morbidities associated with early preterm birth are known, the risks of maternal morbidities in these births remain unclear. Thus, we set out to assess the risk of maternal morbidities associated with early preterm births. Methods: Retrospective cohort study utilizing the United States (US) Natality Live Birth database from the Centers for Disease Control and Prevention (2016–2021). Low-risk singleton pregnancies were included. High-risk conditions such as out-of-hospital births, fetal anomalies, pregestational and gestational diabetes, and hypertensive disorders of pregnancy were excluded. The rates of several maternal morbidities were compared among three gestational age at birth groups: 23 0/7–27 …

Neuroprotective Effect Of L-Dopa-Induced Interleukin-13 On Striatonigral Degeneration In Cerebral Ischemia, Eunhae Jeon, Myeong-Seong Seo, Enkhmaa Lkhagva-Yondon, Yu-Ree Lim, Seung-Woo Kim, Yu Jeong Kang, Jun Seok Lee, Byoung Dae Lee, Rayul Wi, So-Yoon Won, Young Cheul Chung, Eun S Park, Eunhee Kim, Byung Kwan Jin, Myung-Shin Jeon

Faculty, Staff and Student Publications

Levodopa (L-DOPA) treatment is a clinically effective strategy for improving motor function in patients with ischemic stroke. However, the mechanisms by which modulating the dopamine system relieves the pathology of the ischemic brain remain unclear. Emerging evidence from an experimental mouse model of ischemic stroke, established by middle cerebral artery occlusion (MCAO), suggested that L-DOPA has the potential to modulate the inflammatory and immune response that occurs during a stroke. Here, we aimed to demonstrate the therapeutic effect of L-DOPA in regulating the systemic immune response and improving functional deficits in mice with ischemia. Transient MCAO led to progressive degeneration …

Clc-Kb Pore Mutation Disrupts Glycosylation And Triggers Distal Tubular Remodeling, Yogita Sharma, Robin Lo, Viktor N Tomilin, Kotdaji Ha, Holly Deremo, Aishwarya V Pareek, Wuxing Dong, Xiaohui Liao, Svetlana Lebedeva, Vivek Charu, Neeraja Kambham, Kerim Mutig, Oleh Pochynyuk, Vivek Bhalla

Faculty, Staff and Student Publications

Mutations in the CLCNKB gene (1p36), encoding the basolateral chloride channel ClC-Kb, cause type 3 Bartter syndrome. We identified a family with a mixed Bartter/Gitelman phenotype and early-onset kidney failure and by employing a candidate gene approach, identified what we believe is a novel homozygous mutation (CLCNKB c.499G>T [p.Gly167Cys]) in exon 6 of CLCNKB in the index patient. We then validated these results with Sanger and whole-exome sequencing. Compared with wild-type ClC-Kb, the Gly167Cys mutant conducted less current and exhibited impaired complex N-linked glycosylation in vitro. We demonstrated that loss of Gly-167, rather than gain of a mutant Cys, …

A Proteogenomic Analysis Of Cervical Cancer Reveals Therapeutic And Biological Insights, Jing Yu, Xiuqi Gui, Yunhao Zou, Qian Liu, Zhicheng Yang, Jusheng An, Xuan Guo, Kaihua Wang, Jiaming Guo, Manni Huang, Shuhan Zhou, Jing Zuo, Yimin Chen, Lu Deng, Guangwen Yuan, Ning Li, Yan Song, Jia Jia, Jia Zeng, Yuxi Zhao, Xianming Liu, Xiaoxian Du, Yansheng Liu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, Hu Zhou, Zhen Shao, Lingying Wu, Daming Gao

Faculty, Staff and Students Publications

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, …

The Role Of Uncertainty In Illness: Insights Into Psychological Adjustment In Systemic Lupus Erythematosus, Theresa A. Skojec

MUSC Theses and Dissertations

There are currently few studies that directly explore the relationship between uncertainty in illness and psychological adjustment to Systemic Lupus Erythematosus (SLE), highlighting a critical gap in understanding how patients cope with and adjust to the emotional and mental challenges posed by this chronic condition. This dissertation comprises three manuscripts focused on filling this knowledge gap. The first is an integrative review guided by Mishel’s Uncertainty in Illness Theory, which examines how uncertainty affects patients' psychological and emotional well-being during illness and explores strategies to manage or reduce this uncertainty. The integrative review included 27 publications that examined uncertainty in …

The Role Of Microrna-155 As A Biomarker In Diffuse Large B-Cell Lymphoma, Epameinondas Koumpis, Vasileios Georgoulis, Konstantina Papathanasiou, Alexandra Papoudou-Bai, Panagiotis Kanavaros, Evangelos Kolettas, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL …

Comparison Of The Bristol Stool Scale And Modified Version For Children: Use By Providers Vs Children, James Orozco, Mariella M Self, Sara Grisales, Bruno P Chumpitazi, Danita I Czyzewski, Meagan S Mcmullen, Rebecca Berger, Clarissa A Gonzalez, Amber L Cunha, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Accurate report of stool form is essential to diagnosis and assessment of treatment response. The modified Bristol Stool Form Scale for Children (mBSFS-C) classifies stool form into 5 types and is reliable and valid. However, a direct comparison of provider's and children's ratings using the mBSFS-C vs the traditional BSFS that uses 7 stool form types has not been done.

Methods: Pediatric gastroenterology providers and children rated the same 35 stool photographs, reflecting diverse stool forms, using both scales. The order of photograph presentation and scale use were randomized. For each photograph, the most common rating (modal rating) was …

Genotype-Specific Effects Of Elamipretide In Patients With Primary Mitochondrial Myopathy: A Post Hoc Analysis Of The Mmpower-3 Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce Cohen, Gregory M Ennes, Marni J Falk, Amy Goldstein, Gráinne Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russekk Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, Anthony Abbruscato, David A Brown, Alana Sullivan, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Students Publications

BACKGROUND: As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those …

Initiation Of Hearing Aids Use And Incident Dementia Among Mid-To-Late Life Adults: The Health And Retirement Study 2010-2018, Jingkai Wei, Kun Li, Youngran Kim, Rahul Ghosal, Donglan Zhang, Anwar T Merchant, Casey Crump

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Hearing aids may reduce the risk of dementia among individuals with hearing loss. However, no evidence is available from randomized controlled trials (RCTs) on the effectiveness of hearing aids use in reducing incident dementia. Using target trial emulation, we leveraged an existing longitudinal cohort study to estimate the association between hearing aids initiation and risk of dementia.

RESEARCH DESIGN AND METHODS: The Health and Retirement Study was used to emulate target trials among non-institutionalized participants aged ≥50 years with self-reported hearing loss, without dementia at baseline, and without use of hearing aids in the previous 2 years. …

Plasmodium Berghei Liver Stage Parasites Exploit Host Gabarap Proteins For Tfeb Activation, Jacqueline Schmuckli-Maurer, Annina F Bindschedler, Rahel Wacker, Oliver M Würgler, Ruth Rehmann, Timothy Lehmberg, Leon O Murphy, Thanh N Nguyen, Michael Lazarou, Jlenia Monfregola, Andrea Ballabio, Volker T Heussler

Duncan NRI Faculty and Staff Publications

Plasmodium, the causative agent of malaria, infects hepatocytes prior to establishing a symptomatic blood stage infection. During this liver stage development, parasites reside in a parasitophorous vacuole (PV), whose membrane acts as the critical interface between the parasite and the host cell. It is well-established that host cell autophagy-related processes significantly impact the development of Plasmodium liver stages. Expression of genes related to autophagy and lysosomal biogenesis is orchestrated by transcription factor EB (TFEB). In this study, we explored the activation of host cell TFEB in Plasmodium berghei-infected cells during the liver stage of the parasite. Our results …

Genetic Risk Classification For Adults With Aml Receiving Less-Intensive Therapies: The 2024 Eln Recommendations, Hartmut Döhner, Courtney D Dinardo, Frederick R Appelbaum, Charles Craddock, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Lucy A Godley, Robert P Hasserjian, Richard A Larson, Ross L Levine, Yasushi Miyazaki, Dietger Niederwieser, Gert Ossenkoppele, Christoph Röllig, Jorge Sierra, Eytan M Stein, Martin S Tallman, Hwei-Fang Tien, Jianxiang Wang, Agnieszka Wierzbowska, Andrew H Wei, Bob Löwenberg

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.

Insights Into Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Gurpreet Kaur, Ketki Patil, Janam Dave, B Vijayalakshmi Ayyar, Victoria R Tenge, Frederick H Neill, Xi-Lei Zeng, Allison L Speer, Sara C Di Rienzi, Robert A Britton, Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system hindered the study of HuNoV replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We optimized culture media conditions and generated genetically modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present new insights into this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity …

Optimal Management Of Patients With Moderate-To-Severe Inflammatory Bowel Disease, Tugrul Purnak, Atilla Ertan

Faculty, Staff and Student Publications

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and often debilitating condition requiring complex and individualized management. Over the past few decades, advancements in understanding IBD pathophysiology have led to a transformative shift in therapeutic approaches. This article provides a comprehensive overview of the evolution of IBD treatments, from early symptom-focused therapies to modern biologics, small molecule agents, and emerging treatment strategies. We discuss therapeutic goals centered on achieving clinical remission, endoscopic/mucosal healing, and enhancing patient quality of life. Additionally, we explore the rationale for the early and personalized use of biologic therapies …

Firearm Access, Carriage And Use In An Ethnically Diverse Sample Of Young Adults In Texas, Usa, Yu Lu, Elizabeth Baumler, Annalyn Saludares Demello, Leila Wood, Hillary Mcguire, Jeff R Temple

Faculty, Staff and Student Publications

Background Despite the high rates of firearm ownership and firearm-related injuries and mortalities in Southern US states, understandings on the factors contributing to these are lacking.

Methods Using wave 10 (2021) data from a longitudinal study, we examined firearm-related experiences among 636 ethnically diverse young adults (mean age=26 years; 62% female) in Texas, USA.

Results Just over half of participants had ready access to firearms, with 22.3% having carried a firearm outside of their home, 4.9% having been threatened with a firearm by a romantic partner and 4.4% by a non-romantic partner. More firearm access and carriage were reported in …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Comparative Efficacy And Safety Of Transcatheter Versus Mitral-Valve Surgery In Elderly Patients With Mitral Regurgitation: A Systematic Review And Meta-Analysis, Saif Almuzainy, Mohamed Lemine, Rayan Aljubeh, Sami Alsalem

Journal of the Saudi Heart Association

Objectives: Mitral valve surgery is the reference treatment for severe symptomatic mitral regurgitation (MR). Percutaneous mitral valve interventions, such as the MitraClip procedure, offer an alternative, particularly for high-risk patients. The aim of this systematic review and meta-analysis was to analyze the safety and effectiveness of transcatheter mitral valve repair (TMVR) compared to surgical mitral valve repair or replacement (SMVR) in elderly patients with mitral regurgitation. Methods: We searched PubMed, Scopus, Ovid, EBSCO, and ProQuest through July 2024. Eligible studies were randomized controlled trials and observational comparative studies of TMVR versus SMVR for patients with MR, reporting outcomes such as …

Limosilactobacillus Reuteri Ameliorates Maternal Separation Stress In Newborn Mice And Alters Subsequent Adult Behaviour, Z. M. Saleh, B. Okeugo, V. R. Venna, F. W. Blixt, V. A. Quaicoe, E. S. Park, S. Giorgberidze, Meng Luo, Christopher M. Taylor, J. M. Rhoads, Y. Liu

School of Medicine Faculty Publications

Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension …

Leveraging The T2t Assembly To Resolve Rare And Pathogenic Inversions In Reference Genome Gaps, Kristine Bilgrav Saether, Jesper Eisfeldt, Jesse D Bengtsson, Ming Yin Lun, Christopher M Grochowski, Medhat Mahmoud, Hsiao-Tuan Chao, Jill A Rosenfeld, Pengfei Liu, Marlene Ek, Jakob Schuy, Adam Ameur, Hongzheng Dai, Undiagnosed Diseases Network, James Paul Hwang, Fritz J Sedlazeck, Weimin Bi, Ronit Marom, Josephine Wincent, Ann Nordgren, Claudia M B Carvalho, Anna Lindstrand

Faculty, Staff and Students Publications

Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis. Short-read genome sequencing (srGS) can only resolve ∼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the …

The Effect Of A Structural Wellness Intervention On Id Fellows And Faculty, Michael T. Czapka, Christopher Lehmann, John Flores, Erica Mackenzie, Elizabeth Bell, Aniruddha Hazra

Journal of Wellness

Introduction: Physician burnout is prevalent amongst Infectious Diseases (ID) physicians and trainees in the United States. There is limited data assessing the impact of structural interventions in reducing burnout among medical professionals.

Methods: The multifaceted intervention included increased faculty presence over the weekend and faculty support during the week. ID fellows were surveyed before and after the intervention and faculty were surveyed after the intervention using the Maslach Burnout Inventory for Medical Personnel and additional questions regarding wellness and time for education. Pre- and post-intervention responses were compared. Free response answers were analyzed to determine major themes. Metrics of clinical …

Spatiotemporal Mapping Of Auditory Onsets During Speech Production, Garret Lynn Kurteff, Alyssa M Field, Saman Asghar, Elizabeth C Tyler-Kabara, Dave Clarke, Howard L Weiner, Anne E Anderson, Andrew J Watrous, Robert J Buchanan, Pradeep N Modur, Liberty S Hamilton

Faculty, Staff and Students Publications

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared with perception, but whether this differentially affects the onset and sustained temporal profiles is not known. …

High-Coverage Nanopore Sequencing Of Samples From The 1000 Genomes Project To Build A Comprehensive Catalog Of Human Genetic Variation, Jonas A Gustafson, Sophia B Gibson, Nikhita Damaraju, Miranda P G Zalusky, Kendra Hoekzema, David Twesigomwe, Lei Yang, Anthony A Snead, Phillip A Richmond, Wouter De Coster, Nathan D Olson, Andrea Guarracino, Qiuhui Li, Angela L Miller, Joy Goffena, Zachary B Anderson, Sophie H R Storz, Sydney A Ward, Maisha Sinha, Claudia Gonzaga-Jauregui, Wayne E Clarke, Anna O Basile, André Corvelo, Catherine Reeves, Adrienne Helland, Rajeeva Lochan Musunuri, Mahler Revsine, Karynne E Patterson, Cate R Paschal, Christina Zakarian, Sara Goodwin, Tanner D Jensen, Esther Robb, 1000 Genomes Ont Sequencing Consortium, University Of Washington Center For Rare Disease Research (Uw-Crdr), Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, William Richard Mccombie, Fritz J Sedlazeck, Justin M Zook, Stephen B Montgomery, Erik Garrison, Mikhail Kolmogorov, Michael C Schatz, Richard N Mclaughlin, Harriet Dashnow, Michael C Zody, Matt Loose, Miten Jain, Evan E Eichler, Danny E Miller

Faculty, Staff and Students Publications

Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest in using long-read sequencing (LRS) to streamline clinical genomic testing, but the absence of control data sets for variant filtering and prioritization has made tertiary analysis of LRS data challenging. To address this, the 1000 Genomes Project (1KGP) Oxford Nanopore Technologies Sequencing Consortium aims to generate LRS data from at least 800 of the 1KGP samples. Our goal is to use LRS to identify a broader spectrum of variation …

Cardiopulmonary Exercise Testing In Pulmonary Arterial Hypertension And Chronic Thromboembolic Pulmonary Hypertension, Alexis Coulis, Shir Levanon, Gurshaun Randhawa, Yevgeniy Brailovsky, Farhan Raza, Estefania Oliveros

Division of Cardiology Faculty Papers

Cardiopulmonary exercise testing allows for a comprehensive assessment of the mechanism of exercise limitation in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Competitive pathophysiologic mechanisms may affect the clinical interpretation of cardiopulmonary disease as they relate to dyspnea, leg fatigue, and exercise intolerance.

Construction And Evaluation Of A New Rat Reference Genome Assembly, Grcr8, From Long Reads And Long-Range Scaffolding, Kai Li, Melissa L Smith, J Chris Blazier, Kelli J Kochan, Jonathan M D Wood, Kerstin Howe, Anne E Kwitek, Melinda R Dwinell, Hao Chen, Julia L Ciosek, Patrick Masterson, Terence D Murphy, Theodore S Kalbfleisch, Peter A Doris

Faculty, Staff and Student Publications

We report the construction and analysis of a new reference genome assembly for Rattus norvegicus, the laboratory rat, a widely used experimental animal model organism. The assembly has been adopted as the rat reference assembly by the Genome Reference Consortium and is named GRCr8. The assembly has employed 40× Pacific Biosciences (PacBio) HiFi sequencing coverage and scaffolding using optical mapping and Hi-C. We used genomic DNA from a male BN/NHsdMcwi (BN) rat of the same strain and from the same colony as the prior reference assembly, mRatBN7.2. The assembly is at chromosome level with 98.7% of the sequence assigned …

Phase I Dose Escalation Study Of Io-108, An Anti-Lilrb2 Antibody, In Patients With Advanced Solid Tumors, Matthew H Taylor, Aung Naing, John Powderly, Paul Woodard, Luke Chung, Wen Hong Lin, Hongyu Tian, Nathan Siemers, Hong Xiang, Rong Deng, Kyu Hong, Donna Valencia, Tao Huang, Ying Zhu, X Charlene Liao, Xiao Min Schebye, Manish R Patel

Faculty, Staff and Student Publications

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. …

Cladribine-Based Therapy For Acute Myeloid Leukemia In Child, Adolescent, And Early Young Adult Patients: The Md Anderson Cancer Center Experience, David Mccall, Shaikha Alqahtani, Moriah Budak, Irtiza Sheikh, Aaron E Fan, Ramya Ramakrishnan, Cesar Nunez, Michael Roth, Miriam B Garcia, Amber Gibson, Naval Daver, Sofia Garces, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Courtney D Dinardo, Guillermo Montalban Bravo, Guillermo Garcia-Manero, Branko Cuglievan, Tapan Kadia

Faculty, Staff and Student Publications

Background: Cladribine-based combination chemotherapy has demonstrated promising efficacy in patients with relapsed/refractory adult acute myeloid leukemia (AML), prompting its increased utilization in the frontline; in pediatrics, it has been typically reserved for relapsed or refractory cases. While fludarabine has been used more commonly as a purine analog in intensive regimens, cladribine may be an important alternative.

Methods: We performed a retrospective study at MD Anderson Cancer Center from January 2015 to July 2023, which included patients aged 1-21 years with refractory or relapsed AML who received cladribine outside of a transplant conditioning.

Results: A total of 30 patients were included, …