Digital Commons Network^™

Metabolic Impact Of Dietary Glycine Supplementation In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Paul M Yen, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine plays a central role in human metabolism, and an adequate supply is required for synthesizing glutathione (GSH), eliminating excess metabolites as acylglycine via the glycine conjugation detoxification pathway, and maintaining 1-carbon cycle activity. However, glycine is deficient in individuals with severe obesity, which may compromise these pathways and metabolic health. This exploratory study examines whether dietary glycine supplementation could correct glycine deficiency and impairments in glycine-dependent metabolic pathways. 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m2) were treated with dietary glycine (100 mg/kg/day) for two weeks. We found that treatment significantly increased the plasma concentration of glycine …

Cep76 Impairment At The Centrosome-Cilium Interface Contributes To A Spectrum Of Ciliopathies, Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A Lewis, Farid Ullah, Thomas Arbogast, Jackson P Ogden, Madeleine Harion, Marjolaine Willems, Maha S Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E Davis

Faculty, Staff and Students Publications

Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including …

Nucleotide Motif-Guided Selection Of Plasma Microrna Biomarkers In Trauma, Boyang Ren, Ruoxing Li, Chien-Yu Lin, Chanhee Park, Sheng Wang, Andrew O Suen, John Kessler, Shiming Yang, Rosemary Kozar, Lin Zou, Brittney Williams, Ziyi Li, Peter Hu, Wei Chao

Faculty, Staff and Student Publications

Trauma remains a leading cause of morbidity and mortality in part due to complex pathophysiological responses. Yet our abilities to predict these changes are limited. Plasma miRNAs have been proposed as DAMPs that drive immune response and organ injury. Here, we test a panel of plasma miRNAs-selected based on next-generation sequencing and nucleotide motifs identified via a machine-learning algorithm-for their abilities to predict subclinical pathophysiological injuries. We find marked and severity-dependent increases in the miRNA biomarkers following trauma, which are closely associated with various injury markers. AUROC indicates that these biomarkers possess strong diagnostic and predictive abilities in overall trauma …

Visualization Of Lysosomal Membrane Proteins By Cryo Electron Tomography, Bridget M Mcveigh, José J De Jesús-Pérez, Dirk H Siepe, Prerana Gogoi, Shrawan Kumar Mageswaran, Marian Kalocsay, Elaine M Mihelc, Vera Y Moiseenkova-Bell

Faculty, Staff and Student Publications

Lysosomes are essential organelles for cellular homeostasis and signaling, with dysfunction linked to neurological disorders, lysosomal storage diseases, and cancer. While proteomics has advanced our understanding of lysosomal composition, the structural characterization of lysosomal membrane proteins in their native environment remains a significant challenge. Here, we developed a cryo electron tomography workflow to visualize lysosomal membrane proteins within intact, native lysosomal membranes. We isolated endolysosomes by independently targeting two lysosomal membrane proteins, transient receptor potential mucolipin 1 and transmembrane protein 192, enriching organelles that exhibited the expected morphology and proteomic composition of the endolysosomal system. Sub-tomogram averaging enabled the structural …

Intracellular Lactate Dynamics In Drosophila Neurons, Matthew S Price, Elham Rastegari, Richa Gupta, Katie Vo, Travis I Moore, Kartik Venkatachalam

Faculty, Staff and Student Publications

Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigated the effects of nutrient deprivation on lactate dynamics in Drosophila neurons by leveraging the limiting effects of the unstirred layer, a diffusion barrier that forms around cells in culture. We found that neurons constitutively consume lactate when the availability of trehalose, a glucose disaccharide preferred by insects, is limited by the unstirred layer. Acute mechanical disruption of the unstirred layer reduced this reliance on lactate. Through kinetic modeling and experimental validation, we demonstrate that neuronal lactate consumption rates under unstirred layer …

Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley

Children’s Nutrition Research Center Staff Publications

Background: Medical nutrition therapy is fundamental for managing glycemia and weight in type 1 diabetes, yet dietary guidance specific to this population and relevant subgroups is lacking.

Purpose: We synthesized the interventional literature investigating diet patterns for glycemic and weight management in youth and adults with type 1 diabetes, with attention to interindividual variation that suggests the need for precision approaches. The protocol was prospectively registered (CRD42024519941).

Data sources: AMED, CINAHL, Cochrane Library, Ovid MEDLINE, Ovid Embase, Google Scholar, and Web of Science Core Collection were searched from January 2011 to June 2024.

Study selection: Clinical trials ≥4 weeks with …

Two Commonly Reported Incidental Variants In Otc Are Associated With Late-Onset Disease, Steven H Lang, Russell S Lo, Gareth A Cromie, Aimée M Dudley, Nicholas Ah Mew, Kara Simpson, Vernon Reid Sutton, Sandra Darilek, Saima Ali, Matthew T Snyder, Brendan Lee, Ronit Marom, Sandesh C S Nagamani, Lindsay C Burrage

Faculty, Staff and Students Publications

Asymptomatic individuals with pathogenic variants in OTC, the gene encoding ornithine transcarbamylase are increasingly being identified through cascade testing, carrier screening, or as secondary findings from genome-wide sequencing tests. However, guidance for counseling and management of such individuals is currently lacking. We selected two common OTC variants for phenotypic and functional characterization: NM_000531.6:c.118C>T p.(Arg40Cys) and NM_000531.6:c.1061T>G p.(Phe354Cys). The former is the most frequently reported pathogenic/likely pathogenic missense variant present in gnomAD, and the latter has been frequently encountered in our clinical practice. We performed a retrospective chart review at our center, queried the database of the Urea Cycle …

Genetic Determinants And Genomic Consequences Of Non-Leukemogenic Somatic Point Mutations, Joshua S Weinstock, Sharjeel A Chaudhry, Maria Ioannou, Maria Viskadourou, Paula Reventun, Yasminka A Jakubek, L Alexander Liggett, Cecelia Laurie, Jai G Broome, Alyna Khan, Kent D Taylor, Xiuqing Guo, Patricia A Peyser, Eric Boerwinkle, Nathalie Chami, Eimear E Kenny, Ruth J Loos, Bruce M Psaty, Russell P Tracy, Jennifer A Brody, Jeong H Yun, Michael H Cho, Ramachandran S Vasan, Sharon L Kardia, Jennifer A Smith, Laura M Raffield, Aurelian Bidulescu, Emily C O'Brien, Mariza De Andrade, Jerome I Rotter, Stephen S Rich, Russell P Tracy, Yii Der Ida Chen, C Charles Gu, Chao A Hsiung, Charles Kooperberg, Bernhard Haring, Rami Nassir, Rasika Mathias, Alex Reiner, Vijay G Sankaran, Charles J Lowenstein, Thomas W Blackwell, Goncalo R Abecasis, Albert V Smith, Hyun M Kang, Pradeep Natarajan, Siddhartha Jaiswal, Alexander Bick, Wendy S Post, Paul Scheet, Paul Auer, Theodoros Karantanos, Alexis Battle, Marios Arvanitis

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as leukemogenic point mutations or mosaic chromosomal alterations (mCAs), are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we use 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic …

A Case Study Of Ai-Enabled Software As A Medical Device Cleared By The Fda For Assessing Hemorrhage Risk Index (Appraise-Hri) After Trauma, Andrew Frock, Jeffrey T Robbins, Francisco G Vital-Lopez, Valmik Desai, Gheorghe Doros, Barry E Sands, Arunkumar Prabhakaran, Christopher Nemeth, Gregory T Rule, Jason L Sperry, Francis X Guyette, Stephen R Wisniewski, Ernest E Moore, Martin Schreiber, Bellal Joseph, Chad T Wilson, Bryan Cotton, Daniel Ostermayer, Brian G Harbrecht, Mayur B Patel, Suzanne Tamang, Sanjay Malunjkar, David A Spain, Andrew T Reisner, Jonathan D Stallings, Jaques Reifman

Faculty, Staff and Student Publications

Hemorrhage is the leading cause of preventable death on the battlefield, yet combat medics lack clinical decision support systems to help stratify hemorrhage risk in trauma casualties. We previously trained the Automated Processing of the Physiological Registry for Assessment of Injury Severity - Hemorrhage Risk Index (APPRAISE-HRI) software to associate patterns in vital signs (heart rate and blood pressure) collected from trauma patients with three HRI levels: I (low), II (average), or III (high). To independently validate APPRAISE-HRI and obtain U.S. Food and Drug Administration (FDA) clearance, we collected trauma registry and continuous vital sign data from 5895 trauma patients …

A Pooled Sample Study Of Opioid Use Disorder Treatment Wait Time Among A Pregnant Population In New York, Stanley Nkemjika, Gulshan Begum, Bolaji Yoade, Vaibhav Vyas, Henry Onyeaka, Olubusola Olatunji, Olaniyi Olayinka, Ayana Jordan

Faculty, Staff and Student Publications

Background and Aim: Opioid use disorder (OUD) during pregnancy has become a major public health issue, with its prevalence rising significantly in recent years. The incidence of neonatal abstinence syndrome (NAS) has also surged, from 1.5 cases per 1000 hospital births in 1999 to 6.0 cases per 1000 in 2013. This study aims to identify and analyze the concerns faced by pregnant people in accessing OUD treatment on time, specifically focusing on New York.

Methods: The pooled sample of 225,275 individuals represents pregnant patients with OUD who received treatment at substance use disorder (SUD) facilities across New York State between …

Equal Survival For Black Americans With Multiple Myeloma When Appropriately Matched To White Americans, David E Mery, Guido Tricot, Samer Al Hadidi, Yihao Zhan, Cody Ashby, Clyde Bailey, Eric R Siegel, Daisy V Alapat, Hongwei Xu, Sandra Mattox, Caroline Schinke, Maurizio Zangari, Sharmilan Thanendrarajan, Qing Yi, Robert Z Orlowski, Frits Van Rhee, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

No abstract provided.

Protocol For Isolating Patient-Derived Ascites Cells And Extracellular Vesicles From Gastric Cancer Peritoneal Metastases, Yibo Fan, Jody V Vykoukal, Shumei Song, Melissa Pool Pizzi, Gengyi Zou, Katsuhiro Yoshimura, Jiankang Jin, Hiroyuki Katayama, George A Calin, Rebecca E Waters, Qiong Gan, Linghua Wang, Samir Hanash, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Peritoneal carcinomatosis (PC) cells and extracellular vesicles (EVs) from gastric cancer ascites are valuable for studying tumor-stroma interactions. Here, we present a protocol for isolating PC cells and EVs from patient ascites. We describe steps for PC cell culture, iodixanol-based EV purification, electron microscopy, nanoparticle tracking analysis, flow cytometry, and proteomic profiling. This protocol also includes TD-139 loading into exosomes for functional assays to evaluate their role in modulating the tumor microenvironment. For complete details on the use and execution of this protocol, please refer to Fan et al.

Varied Presentations Of Arterial Events In Vascular Ehlers-Danlos Syndrome, Milan Jaiswal, Sara Mansoorshahi, Sharon Zachariah, Thanila Macedo, Alana C Cecchi, Bihong Zhao, L Maximilian Buja, Dianna M Milewicz, Gustavo S Oderich, Rana O Afifi, Akiko Tanaka, Anthony L Estrera, Salman A Arain, Siddharth K Prakash

Faculty, Staff and Student Publications

Spontaneous arterial aneurysms and dissections are relatively common in patients with vascular Ehlers-Danlos syndrome, and arterial rupture accounts for most deaths. Members of the Aortic and Vascular Disease Clinic at UTHealth Houston hold a monthly conference that includes cardiothoracic and vascular surgeons, cardiologists, geneticists, radiologists, and pathologists to formulate multidisciplinary approaches for the management of complex cases. In this case series, we highlight the variable presentations and clinical evolution of complex aortic and vascular disease due to vascular Ehlers-Danlos syndrome.

Estrogen-Related Receptor Alpha Promotes Skeletal Muscle Regeneration And Mitigates Muscular Dystrophy, Thi Thu Hao Nguyen, Ya Xiang Huang, Svitlana Poliakova, Citu Citu, Eira Mann, Danesh H Sopariwala, Zhongming Zhao, Ashok Kumar, Vihang A Narkar

The Brown Foundation: Institute of Molecular Medicine

Skeletal muscle regeneration in chronic muscle diseases such as Duchenne Muscular Dystrophy (DMD) has remained clinically unsurmountable. Estrogen‐related receptor alpha (ERRα) plays a critical role in adult skeletal muscle metabolism and exercise fitness. Whether ERRα activation can drive muscle regeneration and mitigate dystrophy in DMD is not known. We have investigated ERRα signaling in pre‐clinical models of acute muscle injury and DMD. ERRα is induced in differentiating C2C12 myoblast and regenerating muscle. ERRα silencing suppressed proliferation and differentiation in C2C12 myoblasts. RNA sequencing revealed that angiogenic factor and proliferation genes were downregulated by ERRα knockdown in proliferating cells, whereas oxidative …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Differential Bk Channel Potentiation By Vanzacaftor Enantiomers Enables Therapy For Modulator-Ineligible People With Cystic Fibrosis, Nathalie Baumlin, Sumedha Gunewardena, Scott H Randell, Frank T Horrigan, Matthias Salathe

Faculty, Staff and Students Publications

No abstract provided.

Predictors Of Long-Term Follow-Up Clinic Attendance And Continued Engagement Among Survivors Of Cancer In Childhood And Adolescence, Ji Yun Tark, Kayla L Foster, Shawki L Qasim, Omar Shakeel, Alicia Howell, Mary C Shapiro, Abiodun Oluyomi, Zoann E Dreyer, Ashley M Butler, Austin L Brown, Maria M Gramatges

Faculty, Staff and Students Publications

Purpose: Survivorship care is vital to screen for and manage late effects, yet follow-up remains suboptimal. We examined factors associated with long-term survivor clinic (LTSC) nonattendance, delayed initiation, and disengagement at a large, diverse pediatric cancer center.

Methods: We analyzed outcomes in 1138 survivorship-eligible childhood cancer survivors diagnosed between 2011 and 2019. Outcomes included (1) LTSC nonattendance (no visit ≥ 2 years post-treatment), (2) delayed LTSC visit initiation (first visit > 5 years from end of treatment), and (3) LTSC visit disengagement (no follow-up after initial LTSC visit). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with …

Sub-Ciliary Localization Of Cep290 And Effects Of Its Loss In Mouse Photoreceptors During Development, Abigail R. Moye, Michael A. Robichaux, Melina A. Agosto, Alexandre P. Moulin, Alexandra Graff-Meyer, Carlo Rivolta, Theodore G. Wensel

Faculty, Staff and Students Publications

No abstract provided.

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Conversion Of Failed Anatomic Total Shoulder Arthroplasty To Reverse Shoulder Arthroplasty Yields Similar Pain And Functional Outcomes To Primary Reverse Shoulder Arthroplasty But Has A Higher Baseplate Failure Rate: A Matched Cohort Study., Kevin A Hao, Trevor G Simcox, Keegan M Hones, Jonathan O Wright, Thomas W Wright, Tyler Lamonica, Bradley S Schoch, Joseph J King

Faculty, Staff and Student Publications

Background: To investigate whether patients who initially underwent anatomic total shoulder arthroplasty (aTSA) for glenohumeral osteoarthritis and were subsequently revised to reverse TSA (rTSA) due to rotator cuff failure or glenoid loosening ultimately attained a similar clinical outcome compared with those who underwent primary rTSA and identify predictors of poor outcomes in the former population.

Methods: We did a single-center retrospective review of 63 shoulders who underwent revision rTSA after primary aTSA that failed due to glenoid component loosening (n = 32), rotator cuff failure (n = 24), or recurrent instability (n = 7). Pain and functional outcomes at minimum …

Correction: Román-Ríos Et Al., Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Figure Legend [...].

Tng260 Is A Small-Molecule Corest Inhibitor That Sensitizes Stk11-Mutant Tumors To Anti-Pd-1 Immunotherapy, Leanne G Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S Patel, Ke Geng, Reshmee Bhattacharya, Gerald S Falchook, Jonathan W Goldman, Alexander I Spira, Salman R Punekar, David R Spigel, Judy S Wang, Ferdinandos Skoulidis, Janaye Stephens, Mary Meynardie, Jaylen M Powell, Alfonso Lopez, Michela Ranieri, Magdalena A Ploszaj, Yi Jer Tan, Yeuan Ting Lee, Yi Yu, Jiehui Deng, Ting Chen, Patrick Mccarren, Alice Tsai, Suleman S Hussain, Brian Doyon, Kenjie Amemiya, Jacques Ermolieff, Preksha Shahagadkar, Nikitha M Das, Lauren R Flynn, Julie A Shields, Laney Danielczyk, Brian J Mcmillan, Andre Mignault, Samuel R Meier, Hsin-Jung Wu, David J Guerin, Douglas A Whittington, Chengyin Min, Iga Sienczylo, John P Maxwell, Heather J Dibenedetto, Hideo Watanabe, Brian B Haines, Alan Huang, Adam Crystal, Jannik N Andersen, Xinyuan Wu, Kwok-Kin Wong

Faculty, Staff and Student Publications

Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacetylase 1 as a target to reverse anti–PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity exceeding previously generated inhibitors in this class in preclinical studies. Treatment with TNG260 led to increased expression of immunomodulatory genes in STK11-deficient cancer cells. When combined with anti–PD-1, TNG260 induced immune-mediated stasis and/or regression in STK11 …

Introducing Mcodegpt As A Zero-Shot Information Extraction From Clinical Free Text Data Tool For Cancer Research, Kai Zhang, Tongtong Huang, Bradley A Malin, Travis Osterman, Qi Long, Xiaoqian Jiang

Faculty, Staff and Student Publications

Background: The vast amount of natural language clinical notes about patients with cancer presents a challenge for efficient information extraction, standardization, and structuring. Traditional NLP methods require extensive annotation by domain experts for each type of named entity and necessitate model training, highlighting the need for an efficient and accurate extraction method.

Methods: This study introduces a tool based on the Large Language Model (LLM) for zero-shot information extraction from cancer-related clinical notes into structured data aligned with the minimal Common Oncology Data Elements (mCODE™) structure. We utilize the zero-shot learning capabilities of LLMs for information extraction, eliminating the need …

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Probabilistic Data Linkage To Study The Epidemiology Of Unintentional Fatal Drowning In A Large Metropolitan Region, Rohit P Shenoi, Ned Levine, Elizabeth A Camp, Linh Nguyen, Sandra Mckay, Shaila Zaman

Faculty, Staff and Students Publications

Background: It is difficult to study the epidemiology of drowning at the regional level because of multiple data sources, many of which have a high degree of unstandardized and missing data. We aimed to link multiple datasets to identify demographics and geographic locations of unintentional fatal drowning in a metropolitan region and compare linked data with vital statistic data.

Methods: This cross-sectional study included unintentional drowning fatalities among persons of all ages in metropolitan Houston between 2016 and 2022. Probabilistic linking was used to link multiple datasets and geographical mapping to identify drowning locations. The effectiveness of data linkage was …

Generative Modeling For Interpretable Anomaly Detection In Medical Imaging: Applications In Failure Detection And Data Curation, Mckell E Woodland, Mais Altaie, Caleb S O'Connor, Austin H Castelo, Olubunmi C Lebimoyo, Aashish C Gupta, Joshua P Yung, Paul E Kinahan, Clifton D Fuller, Eugene J Koay, Bruno C Odisio, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

This work aims to leverage generative modeling-based anomaly detection to enhance interpretability in AI failure detection systems and to aid data curation for large repositories. For failure detection interpretability, this retrospective study utilized 3339 CT scans (525 patients), divided patient-wise into training, baseline test, and anomaly (having failure-causing attributes—e.g., needles, ascites) test datasets. For data curation, 112,120 ChestX-ray14 radiographs were used for training and 2036 radiographs from the Medical Imaging and Data Resource Center for testing, categorized as baseline or anomalous based on attribute alignment with ChestX-ray14. StyleGAN2 networks modeled the training distributions. Test images were reconstructed with backpropagation and …

The Clingen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications For Classification Of Variants In Ada, Dclre1c, Il2rg, Il7r, Jak3, Rag1, And Rag2, Vanessa C Jacovas, Michelle Zelnick, Shannon Mcnulty, Justyne E Ross, Namrata Khurana, Xueyang Pan, Alejandro Nieto, Shiloh Martin, Benjamin Mclean, Marwa A Elnagheeb, Morton J Cowan, Jennifer M Puck, Mike S Hershfield, James Verbsky, Jolan Walter, Eric J Allenspach, Alice Y Chan, Nicolai S C Van Oers, Rajarshi Ghosh, Megan Piazza, Bo Yuan, Luigi D Notarangelo, Britt A Johnson, Ivan K Chinn, Severe Combined Immunodeficiency Variant Curation Expert Panel

Faculty, Staff and Students Publications

Purpose: This collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America: ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2.

Methods: The SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines. These …

Yx0798 Is A Highly Potent, Selective, And Orally Effective Cdk9 Inhibitor For Treating Aggressive Lymphoma, Vivian Jiang, Yu Xue, Hong Kim, Qingsong Cai, Tianci Zhang, Lei Nie, Joseph Mcintosh, Yang Liu, Haiying Chen, Jia Zhou, Michael Wang

Faculty, Staff and Student Publications

Nongenetic transcription evolution has been increasingly explored and recognized to drive tumor cell progression and therapeutic resistance. As the regulation hub of transcription machinery, cyclin-dependent kinase 9 (CDK9) is the gatekeeper of RNA polymerase II transcription, and CDK9 dysfunction results in transcriptomic reprogramming and tumor cell progression. We recently reported that the heat shock protein 90 (HSP90)-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma (MCL) through transcriptomic reprogramming. We also showed that targeting CDK9 by AZD4573 and enitociclib is a safe and effective treatment in preclinical Mantle Cell Lymphoma (MCL) models, supporting CDK9 as a valid therapeutic target for …

Optimizing Genetic Ancestry Adjustment In Dna Methylation Studies: A Comparative Analysis Of Approaches, Kira D Höffler, Seyma Katrinli, Matthew W Halvorsen, Anne-Kristin Stavrum, Kevin S O'Connell, Alexey Shadrin, Srdjan Djurovic, Ole A Andreassen, James J Crowley, Jan Haavik, Kristen Hagen, Gerd Kvale, Kerry Ressler, Bjarne Hansen, Jair C Soares, Gabriel R Fries, Alicia K Smith, Stéphanie Le Hellard

Faculty, Staff and Student Publications

Background: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry.

Methods: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control …