Digital Commons Network^™

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 …

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 …

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 …

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.

Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan

Wills Eye Hospital Papers

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we …

Role Of M6a Mrna Methylation In Plant Defense, Rakesh Srivastava, Niraj Lodhi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

N6-methyladenosine (m⁶A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m⁶A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m⁶A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m⁶A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host–pathogen arms race. …

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

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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 …

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 …

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.

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.

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 …

Unveiling The Potential Of Marine Peptides In Leukemia: Mechanistic Insights And Future Horizon In Peptide Research, Salman Ahmed, Waqas Alam, Khalaf Alsharif, Michael Aschner, Esra Küpeli̇ Akkol, Mamdouh Allahyani, Hayaa Alhuthali, Luci̇ano Saso, Esra Gi̇zem Türkcanoğlu, Haroon Khan

Turkish Journal of Medical Sciences

Leukemia is a malignant disorder that affects the bone marrow and blood. It is frequently diagnosed in adults, with a higher incidence in males than females. Globally, it ranks as the 15th most widespread cancer and is the 11th leading cause of cancer-related fatalities. The intensity and severity of treatment have increased, leading to a rise in relapse rates, toxicity, and adverse health effects. Therefore, there is a critical need for new treatments. The antileukemic properties of natural compounds have been extensively studied. Aquatic organisms are a rich source of potential medicinal compounds. Anticancer peptides offer an ideal treatment approach …

Assessment Of Alterations In Regional Homogeneity And Amplitude Of Low-Frequency Fluctuations In Children With Dyslexia ​, Esra Demi̇rci̇, Şeri̇fe Gengeç Benli̇, Semra İçer, Zeynep Ak, Ebru Aker, Zehra Fi̇li̇z Karaman

Turkish Journal of Medical Sciences

Background/aim: Exploratory methods in neuroimaging are gaining increasing attention for revealing functional connectivity structures across the entire brain. This study aims to contribute to the understanding of the functional mechanisms underlying dyslexia, along with the effects of specialized education for dyslexia treatment, by utilizing measures such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF).

Materials and methods: Resting-state functional magnetic resonance imaging data were collected from three groups of Turkish-speaking children aged 7–12: diagnosed with dyslexia for the first time (Dys, n = 19), children with dyslexia who received specialized education (EDys, n = 20), …

A Comparative Study Of Diagnostic Performance In Shoulder Pain: Clinical Tests Versus Ultrasonography And Magnetic Resonance Imaging, Yasemi̇n Tombak, Özgür Zeli̇ha Karaahmet, Ayşegül Tombak, Ömer Ata, Eda Gürçay

Turkish Journal of Medical Sciences

Background/aim: Shoulder pain is common and often evaluated with physical examination tests, yet their diagnostic accuracy remains controversial. The aim of this cross-sectional study was to determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) rates of clinical test results in patients with shoulder pain, based on ultrasonography (US) and magnetic resonance imaging (MRI) findings as reference diagnostic methods.

Materials and methods: The study included 78 patients who had complaints of shoulder pain. All patients underwent physical examinations and specific clinical tests (such as Neer and Jobe tests) to reveal shoulder pathologies, and US and MRI …

Reliability Of Handheld Autorefractometers In Patients After Cataract Surgery ​, Ayça Küpeli̇ Çinar, Abdulkadi̇r Can Çinar, Hande Güçlü

Turkish Journal of Medical Sciences

Background/aim: Accurate postoperative refraction assessment is essential for optimal visual rehabilitation after cataract surgery. Although handheld autorefractometers (HH-ARMs) are widely used in pediatric and uncooperative patients, their reliability in adults after cataract surgery remains uncertain. This study compared refractive outcomes obtained with a HH-ARM (Mediworks V100; Mediworks, Guangzhou, China) and a TB-ARM (Canon RK-F2; Canon Inc., Tokyo, Japan) to evaluate the clinical applicability of HH-ARM in this population.

Materials and methods: This prospective study included 150 eyes of 150 patients (aged 55–85 years) who underwent uncomplicated phacoemulsification with intraocular lens (IOL) implantation. At 1 month postoperatively, spherical value (SV), cylindrical …

Ai Performance In Emergency Medicine Fellowship Examination: Comparative Analysis Of Chatgpt-4o, Gemini 2.0, Claude 3.5, And Deepseek R1 Models, İshak Şan, Medi̇ne Akkan Öz, Mehmet Yortanli, Murat Genç, Bensu Bulut, Ayşenur Gür, Rami̇z Yazici, Hüseyi̇n Mutlu, Mustafa Önder Gönen

Turkish Journal of Medical Sciences

Background/aim: This study evaluated the accuracy rates and response consistency of four different large language models (ChatGPT- 4o, Gemini 2.0, Claude 3.5, and DeepSeek R1) in answering questions from the Emergency Medicine Fellowship Examination (YDUS), which was administered for the first time in Türkiye.

Materials and methods: In this observational study, 60 multiple-choice questions from the Emergency Medicine YDUS administered on 15 December 2024, were classified as knowledge-based (n = 26), visual content (n = 2), and case-based (n = 32). Each question was presented three times to the four large language models. The models’ accuracy rates were evaluated according …

Fear Of Covid-19 And Hygiene Behaviors: A Study Of Secondary School Students In İstanbul ​, Zozan Göksu, Hayri̇ye Kirkoyun Uysal, Mehmet Demi̇rci̇, Di̇lek Dülger, Seda Eki̇ci̇

Turkish Journal of Medical Sciences

Background/aim: This study investigates the relationship between fear of COVID-19, measured using the Fear of COVID-19 Scale (FCV-19S), and the hygiene behaviors of secondary school students, assessed with the Hygiene Behavior Scale (HBS).

Materials and methods: Included in this cross-sectional study were 206 secondary school students. The study data were analyzed using multivariate linear regression.

Results: No relationship was found between the fear of COVID-19 scale (FCV-19S) score of the student sample and the mean total HBS and subdimension values (p > 0.05). It was noted that positive hygiene behaviors decreased as the scale score increased. Students with retired mothers scored …

Validation Of The Turkish Version Of The Assessment Of Systemic Sclerosis-Associated Raynaud’S Phenomenon (Asrap) ​, Duygu Temi̇z Karadağ, Şeyma Yilmaz, Betül Di̇kkanoğlu Demi̇rok, John D. Pauling, Ayten Yazici, Ayşe Çefle

Turkish Journal of Medical Sciences

No abstract provided.

Cultural Adaptation And Psychometric Characteristics Of The Child Oral And Motor Proficiency Scale (Chomps)-Turkish Version, Ebru Umay, Si̇bel Eyi̇gör, Damla Cankurtaran, Sema Kalkan, Ni̇hal Tezel, Cuma Uz, Şükran Güzel, Fatma Balli Uz, Güler Gözpinar, Recep Gayir, Fatma Nazli, Keri̇m Demi̇rsöz, Ece Ünlü Akyüz, Britt Pados

Turkish Journal of Medical Sciences

Background/aim: The child oral and motor proficiency scale (ChOMPS) is a parent-reported assessment that evaluates a child’s eating and drinking skills within the framework of all related motor functions. It has been found to be useful in research studies and recommended in reviews. The purpose of this study was to perform the translation and cultural adaptation of the English version of the ChOMPS to Turkish and conduct psychometric testing of the ChOMPS–Turkish version, including reliability and validity.

Materials and methods: This study was conducted with 185 children. Cronbach’s α, corrected item-to-total correlations, coefficient of variation, and Cronbach’s α when one …

Hesperidin Efficacy Of Epidural Fibrosis In A Post Laminectomy Rat Model: An Experimental Study, Emrah Keski̇n, Mehmet Seli̇m Gel

Turkish Journal of Medical Sciences

Background/aim: Epidural fibrosis (EF) plays a significant role in the development of failed back surgery syndrome (FBSS). This study evaluates the antifibrotic effect of hesperidin, a citrus-derived bioflavonoid, within a rat laminectomy model.

Materials and methods: Thirty-two female Wistar albino rats were randomized into four groups (n = 8 each). Group 1 received laminectomy alone (control); Group 2 received a gelatin sponge; Groups 3 and 4 intraperitoneally received 50 mg/kg and 100 mg/kg of hesperidin, respectively, for 7 days post-laminectomy. After 6 weeks, epidural tissues were assessed histopathologically, and hydroxyproline levels were measured.

Results: Group 4 showed significantly lower EF …

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 …

A Social Media Campaign And Web-Based Survey About Prostate Cancer Genetics: Mixed Methods Study, Amy Leader, Stacy Loeb, Preethi Selvan, Ashley Hunter, Rebecca Hartman, Scott Keith, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population.

OBJECTIVE: There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the …

Landscape And Clinicopathologic Features Of Ras Pathway Mutations In Chronic Myelomonocytic Leukemia, Guillermo Montalban-Bravo, Sanam Loghavi, Ziyi Li, Kelly Chien, Rashmi Kanagal-Shamanna, Alex Bataller, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Koji Sasaki, Gautam Borthakur, Mahesh Swaminathan, Courtney Dinardo, Tapan Kadia, Farhad Ravandi, Naval Daver, Nicholas Short, Naveen Pemmaraju, Ghayas Issa, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford Csizmar, Hassan Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, Carlos Bueso-Ramos, Ayalew Tefferi, Hagop Kantarjian, Guillermo Garcia-Manero, Mrinal M Patnaik

Faculty, Staff and Student Publications

RAS pathway (RASp) mutations induce proliferative features, and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASp mutations remain unexplored. To characterize the landscape, architecture, and implications of unique RASp mutations in CMML, we evaluated a cohort of 814 patients with CMML. We identified 461 RASp mutations among 342 patients (42%). N/KRAS and CBL mutations were the most common, frequently involved the P-loop or RING domains, respectively, and frequently appeared as dominant events (63% and 65%, respectively). BRAF, NF1, and PTPN11 mutations spanned throughout the gene structure, and frequently appeared as subclonal …

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 …

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 …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …