Medical Specialties Commons^™

Aptamers As Potential Therapeutic Tools For Ovarian Cancer: Advancements And Challenges, Wojciech Szymanowski, Anna Szymanowska, Anna Bielawska, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo, Paola Amero

Faculty, Staff and Student Publications

Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug …

Late-Gadolinium Enhancement Is Common In Older Pediatric Heart Transplant Recipients And Is Associated With Lower Ejection Fraction, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Melanie Sojka, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure and cumulative rejection history in pediatric heart transplant recipients (PHTR) are associated with myocardial fibrosis on endomyocardial biopsy (EMB). Cardiovascular magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of future adverse clinical events including hospitalization and death. We describe the prevalence, pattern, and extent of LGE on CMR in a cohort of PHTR and its associations with recipient and graft characteristics.

METHODS: This was a retrospective study of consecutive PHTR who underwent …

Randomized Clinical Trial Of Low Dose Suramin Intravenous Infusions For Treatment Of Autism Spectrum Disorder, David Hough, Alice R Mao, Michael Aman, Reymundo Lozano, Constance Smith-Hicks, Veronica Martinez-Cerdeno, Michael Derby, Zachary Rome, Niel Malan, Robert L Findling

Faculty, Staff and Students Publications

Background: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses.

Methods: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 …

Mechanistic Toxicology In Light Of Genetic Compensation, Mary Jane Elizalde, Daniel A Gorelick

Faculty, Staff and Students Publications

Mechanistic toxicology seeks to identify the molecular and cellular mechanisms by which toxicants exert their deleterious effects. One powerful approach is to generate mutations in genes that respond to a particular toxicant, and then test how such mutations change the effects of the toxicant. CRISPR is a rapid and versatile approach to generate mutations in cultured cells and in animal models. Many studies use CRISPR to generate short insertions or deletions in a target gene and then assume that the resulting mutation, such as a premature termination codon, causes a loss of functional protein. However, recent studies demonstrate that this …

Molecular Mechanisms Of Twist1-Regulated Transcription In Emt And Cancer Metastasis, Xiaobin Yu, Tao He, Zhangwei Tong, Lan Liao, Shixia Huang, Walid D Fakhouri, Dean P Edwards, Jianming Xu

Faculty, Staff and Students Publications

TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to …

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …

Machine Learning Methods For Endocrine Disrupting Potential Identification Based On Single-Cell Data, Zahir Aghayev, Adam T Szafran, Anh Tran, Hari S Ganesh, Fabio Stossi, Lan Zhou, Michael A Mancini, Efstratios N Pistikopoulos, Burcu Beykal

Faculty, Staff and Students Publications

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example. The mechanistic stages of the estrogenic transcriptional activity can be measured with high content/high throughput microscopy-based biosensor assays at the single-cell level, which …

Plasma Metabolomics And Quantitative Interstitial Abnormalities In Ever-Smokers, Bina Choi, Raúl San José Estépar, Suneeta Godbole, Jeffrey L Curtis, Jennifer M Wang, Rubén San José Estépar, Ivan O Rosas, Jared R Mayers, Brian D Hobbs, Craig P Hersh, Samuel Y Ash, Meilan K Han, Russell P Bowler, Kathleen A Stringer, George R Washko, Wassim W Labaki

Faculty, Staff and Students Publications

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.

METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles …

Identification Of Blood Protein Biomarkers Associated With Prostate Cancer Risk Using Genetic Prediction Models: Analysis Of Over 140,000 Subjects, Hua Zhong, Jingjing Zhu, Shuai Liu, Dalia H Ghoneim, Praveen Surendran, Tao Liu, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Herbert Yu, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant …

Repurposing Egfr Inhibitors For Oral Cancer Pain And Opioid Tolerance, Maria Daniela Santi, Morgan Zhang, Naijiang Liu, Chi T Viet, Tongxin Xie, Dane D Jensen, Moran Amit, Huilin Pan, Yi Ye

Faculty, Staff and Student Publications

Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how …

A Qualitative Study On Parenting Practices To Sustain Adolescent Health Behaviors In American Indian Families, Christine Hodgson, Dylan Decker, Teresia M O'Connor, Melanie Hingle, Francine C Gachupin

Children’s Nutrition Research Center Staff Publications

American Indian (AI) adolescents who practice healthy behaviors of sleep, nutrition, physical activity, and limited screen time can lower their lifetime risk of diet-sensitive disease. Little is known about how AI parenting practices influence the health behaviors of youth. The objective of this qualitative study was to explore how a group of AI parents of youths at risk of disease influenced their youth’s health behaviors after a family intervention. A secondary objective was to understand the role of AI parents in supporting and sustaining health behavior change in their youths following the intervention. Semi-structured in-depth interviews were conducted with AI …

Neglected Tropical Disease Vaccines: Hookworm, Leishmaniasis, And Schistosomiasis, Peter J Hotez, Maria Elena Bottazzi, Paul M Kaye, Bruce Y Lee, Karl Philipp Puchner

Faculty, Staff and Students Publications

No abstract provided.

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as …

Language Nativeness Modulates Physiological Responses To Moral Vs Immoral Concepts In Chinese-English Bilinguals: Evidence From Event-Related Potential And Psychophysiological Measures, Fei Gao, Chenggang Wu, Hengyi Fu, Kunyu Xu, Zhen Yuan

Faculty, Staff and Student Publications

Morality has been an integral part of social cognition and our daily life, and different languages may exert distinct impacts on human moral judgment. However, it remains unclear how moral concept is encoded in the bilingual brain. This study, therefore, aimed to explore the emotional and cognitive involvement of bilingual morality judgement by using combined event-related potential (ERP) and psychophysiological (including skin, heart, and pulse) measures. In the experiment, thirty-one Chinese-English bilingual participants were asked to make moral judgments in Chinese and English, respectively. Our results revealed increased early frontal N400 and decreased LPC in L1 moral concept encoding as …

Tuberculosis Screening In Migrants To The Eu/Eea And Uk, Niklas Köhler, Anca Vasiliu, Anna Maria Mandalakas, Leonardo Martinez, Christoph Lange

Faculty, Staff and Students Publications

No abstract provided.

Gut Microbiota Composition And Diversity Before, During, And Two Months After Rifamycin-Based Tuberculosis Preventive Therapy, Marie Nancy Séraphin, Julia Bellot, Emily Klann, Maria Ukhanova, Florence G Saulsberry, Charles A Peloquin, Volker Mai

Faculty, Staff and Student Publications

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after …

Potentiation Of Apoptosis In Drug-Resistant Mantle Cell Lymphoma Cells By Mcl-1 Inhibitor Involves Downregulation Of Inhibitor Of Apoptosis Proteins, Yijing Li, Heng-Huan Lee, Vivian Changying Jiang, Yuxuan Che, Joseph Mcintosh, Alexa Jordan, Jovanny Vargas, Tianci Zhang, Fangfang Yan, Margaret Elizabeth Simmons, Wei Wang, Lei Nie, Yixin Yao, Preetesh Jain, Michael Wang, Yang Liu

Faculty, Staff and Student Publications

Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption …

Racial Disparities In Mit Family Translocation Renal Cell Carcinoma, Xiaofan Lu, Nassim Tawanaie Pour Sedehi, Xiaoping Su, Fangrong Yan, Omar Alhalabi, Nizar M Tannir, Gabriel G Malouf

Faculty, Staff and Student Publications

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian …

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

Conformational Ensemble-Dependent Lipid Recognition And Segregation By Prenylated Intrinsically Disordered Regions In Small Gtpases, Mussie K Araya, Alemayehu A Gorfe

Faculty, Staff and Student Publications

We studied diverse prenylated intrinsically disordered regions (PIDRs) of Ras and Rho family small GTPases using long timescale atomistic molecular dynamics simulations in an asymmetric model membrane of phosphatidylcholine (PC) and phosphatidylserine (PS) lipids. Here we show that conformational plasticity is a key determinant of lipid sorting by polybasic PIDRs and provide evidence for lipid sorting based on both headgroup and acyl chain structures. We further show that conformational ensemble-based lipid recognition is generalizable to all polybasic PIDRs, and that the sequence outside the polybasic domain (PBD) modulates the conformational plasticity, bilayer adsorption, and interactions of PIDRs with membrane lipids. …

Comparison Of Non-Laser And Laser Transvenous Lead Extraction: A Systematic Review And Meta-Analysis, Zaki Akhtar, Christos Kontogiannis, Georgios Georgiopoulos, Christoph T Starck, Lisa W M Leung, Sun Y Lee, Byron K Lee, Sreenivasa R K Seshasai, Manav Sohal, Mark M Gallagher

Faculty, Staff and Student Publications

AIMS: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis.

METHODS AND RESULTS: We searched Medline, Embase, Scopus, ClinicalTrials.gov, and CENTRAL databases for TLE studies published between 1991 and 2021. From the included 68 studies, safety and efficacy data were carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR), and pooled rates were synthesized from eligible studies to compare …

Established And Emerging Device Therapy In Heart Failure: Cardiac Contractility Modulation, Justin Haloot, Mihail G Chelu

The Texas Heart Institute Journal

No abstract provided.

Rare De Novo Gain-Of-Function Missense Variants In Dot1l Are Associated With Developmental Delay And Congenital Anomalies, Zelha Nil, Ashish R Deshwar, Yan Huang, Scott Barish, Xi Zhang, Sanaa Choufani, Polona Le Quesne Stabej, Ian Hayes, Patrick Yap, Chad Haldeman-Englert, Carolyn Wilson, Trine Prescott, Kristian Tveten, Arve Vøllo, Devon Haynes, Patricia G Wheeler, Jessica Zon, Cheryl Cytrynbaum, Rebekah Jobling, Moira Blyth, Siddharth Banka, Alexandra Afenjar, Cyril Mignot, Florence Robin-Renaldo, Boris Keren, Oguz Kanca, Xiao Mao, Daniel J Wegner, Kathleen Sisco, Marwan Shinawi, Undiagnosed Disease Network, Michael F Wangler, Rosanna Weksberg, Shinya Yamamoto, Gregory Costain, Hugo J Bellen

Faculty, Staff and Students Publications

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L …

Prognostic Value Of Integrative Genomic Approaches For Idh-Mutant Gliomas, Marco Gallo

Faculty, Staff and Students Publications

No abstract provided.

Tfeb And Tfe3 Control Glucose Homeostasis By Regulating Insulin Gene Expression, Adrien Pasquier, Nunzia Pastore, Luca D'Orsi, Rita Colonna, Alessandra Esposito, Veronica Maffia, Rossella De Cegli, Margherita Mutarelli, Susanna Ambrosio, Gennaro Tufano, Antonio Grimaldi, Marcella Cesana, Davide Cacchiarelli, Nathalie Delalleau, Gennaro Napolitano, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

To fulfill their function, pancreatic beta cells require precise nutrient-sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene …

The Prognostic Role Of Platelet-To-Lymphocyte Ratio In Acute Coronary Syndromes: A Systematic Review And Meta-Analysis, Michal Pruc, Frank William Peacock, Zubaid Rafique, Damian Swieczkowski, Krzysztof Kurek, Monika Tomaszewska, Burak Katipoglu, Maciej Koselak, Basar Cander, Lukasz Szarpak

Faculty, Staff and Students Publications

This study aimed to investigate the potential prognostic role of the platelet-to-lymphocyte (PLR) ratio in patients presenting with suspected acute coronary syndromes (ACS). A systematic search of PubMed Central, Scopus, EMBASE, and the Cochrane Library from conception through 20 August 2023 was conducted. We used odds ratios (OR) as the effect measure with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with a 95% CI for continuous data. If I2 was less than 50% or the p value of the Q tests was less than 0.05, a random synthesis analysis was conducted. Otherwise, a fixed pooled meta-analysis …

Srcap Mutations Drive Clonal Hematopoiesis Through Epigenetic And Dna Repair Dysregulation, Chun-Wei Chen, Linda Zhang, Ravi Dutta, Abhishek Niroula, Peter G Miller, Christopher J Gibson, Alexander G Bick, Jaime M Reyes, Yi-Tang Lee, Ayala Tovy, Tianpeng Gu, Sarah Waldvogel, Yi-Hung Chen, Bryan J Venters, Pierre-Olivier Estève, Sriharsa Pradhan, Michael-Christopher Keogh, Pradeep Natarajan, Koichi Takahashi, Adam S Sperling, Margaret A Goodell

Faculty, Staff and Students Publications

Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead …

Tunnel-Free Acromioclavicular Joint Reconstruction Is Associated With Improved Initial Reduction And Higher Patient Satisfaction, Brittany A Olsen, Joshua W Rollins, Daniel H Ngo, James M Gregory

Faculty, Staff and Student Publications

BACKGROUND: Many surgical techniques have been described for acromioclavicular (AC) joint reconstruction. Creation of bone tunnels through the clavicle or coracoid has been shown to be a risk factor for fracture. Use of an AC reconstruction technique that does not create bone tunnels may obviate this risk. This study aims to evaluate clinical outcomes of AC joint reconstruction using a tunnel-free technique compared to reconstruction using a cortical button and clavicular drill holes.

METHODS: Consecutive patients who underwent AC joint reconstruction by a single surgeon in a subspecialty referral practice were included. One group of patients received cortical button fixation …

Multimodal Analysis Of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury, Finian Keleher, Hannah M Lindsey, Rebecca Kerestes, Houshang Amiri, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Carrie Esopenko, Linda Ewing-Cobbs, Christopher C Giza, Naomi J Goodrich-Hunsaker, Cooper B Hodges, Kristen R Hoskinson, Andrei Irimia, Marsh Königs, Jeffrey E Max, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Adam T Schmidt, Dan J Stein, Stacy J Suskauer, Ashley L Ware, Anne L Wheeler, Brandon A Zielinski, Paul M Thompson, Ian H Harding, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.

Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.

Design, setting, and participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or …