Medical Sciences Commons^™

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, …

Investigating A Mediterranean Dietary Pattern With White Potatoes On Cardiometabolic Health In Adults With Pre-Diabetes From Diverse Racial And Ethnic Backgrounds, Sedona Gronna, Neda S. Akhavan, Sara K. Rosenkranz, Richard R. Rosenkranz

Undergraduate Research Symposium Posters

In the United States, one in three adults has pre-diabetes, and 80% are unaware that they are at risk of developing type-2 diabetes (T2D). Elevated blood glucose levels are associated with an increased risk of heart disease, obesity, dyslipidemia, and hypertension. African-American and Hispanic individuals are disproportionately affected by pre-diabetes and its complications, such as arterial stiffness and obesity, compared to Caucasians. Approximately 70% of those with pre-diabetes may develop T2D, therefore it is crucial to find effective ways to manage and reverse these conditions. Potatoes, which contain a good source of resistant starch, potassium, and other beneficial nutrients, might …

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, …

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 …

Modulation Of Monocyte Effector Functions And Gene Expression By Human Cytomegalovirus Infection, Matthew Planchon, Jay Fishman, Joseph El Khoury

SKMC Student Presentations and Publications

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) …

Legal Disputes Over Frozen Embryos After Dobbs: A Retrospective Study Of Claims, Contracts, And Liability In Cases Of Divorce Or Separation, Gerard Letterie, Dov Fox

Pace Law Review

This study reviewed legal claims and clinic liability over disputed frozen embryos in cases of divorce or separation. Our data shows that one-third of cases had no prior arrangement regarding disposition about what to do in the event of separation or divorce. When agreements were in place they were rarely clear enough to determine the court’s resolution in these cases. In a post-Dobbs era, absence of adequate guidance could have significant implications regarding liability for all parties.

Dobbs And Sterilization Decision-Making: Understanding The Coercive Spillover Effects In Reproductive Choice, Thomas Wilson Williams

Pace Law Review

The Supreme Court majority in Dobbs v. Jackson Women’s Health Organization argued their decision would have limited impact beyond abortion rights. This Article examines how Dobbs and subsequent state abortion restrictions are likely to increase women’s reliance on permanent sterilization procedures, particularly among already marginalized populations. Drawing on emerging data and historical context, I argue that some post-Dobbs sterilizations should be understood as effectively coerced by state policies, implicating reproductive justice concerns and potentially undermining fundamental rights established in Skinner v. Oklahoma. Then, I demonstrate how interdisciplinary bioethics frameworks and methodologies can help courts better understand the full …

Teen Dating Violence And The Covid-19 Pandemic: Trends From A Longitudinal Study In Texas, Leila Wood, Elizabeth Baumler, Morgan E Pettyjohn, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Teen dating violence (TDV) is a global public health and safety issue causing health impacts to youth people. This study aimed to examine: (1) the impact of the pandemic on TDV victimisation rates and (2) socioecological factors associated with sustained risk for TDV victimisation during the first year of COVID-19.

Methods: Data are from an ongoing randomised controlled trial of a TDV prevention programme in Texas (n=2768). We conducted annual assessments in 2019-2021. We used regression modelling to assess demographic, individual, peer and family factors associated with TDV risks.

Results: TDV rates declined from 11.9% in 2019 to 5.2% …

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 …

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 …

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 …

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.

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 …

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 …

Smartphone Haptics Can Uncover Differences In Touch Interactions Between Asd And Neurotypicals, Ivonne Monarca, Franceli L. Cibrian, Isabel López Hurtado, Monica Tentori

Engineering Faculty Articles and Research

Utilizing touch interactions from smartphones for gathering data and identifying digital markers for screening and monitoring neurological disorders, such as Autism Spectrum Disorder (ASD), is an emerging area of research. Smartphones provide multiple benefits for this kind of study, including unobtrusive data collection via built-in sensors, integrated haptic feedback systems, and the capability to create specialized applications. Acknowledging the significant yet understudied presence of tactile processing differences in individuals with ASD, we designed and developed Feel and Touch, a mobile game that leverages the haptic capabilities of smartphones. This game provides vibrotactile feedback in response to touch interactions and collects …

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 …

Immune Responses Drive Chorioretinitis And Retinal Pathology After Neonatal Cmv Infection, Jessica L. Mccord, John Y.S. Han, Ross E. Staudt, Nancy J. Philp Phd, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T …

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 …

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 …

Mitigating Neuroinflammation In Cognitive Areas: Exploring The Impact Of Hmg-Coa Reductase Inhibitor, Carlos Henrique Rocha Catalão, Luis Henrique Angenendt Da Costa, Jonathas Rodrigo Dos Santos, Luciane Carla Alberici, Luiz Luciano Falconi-Sobrinho, Norberto Cysne Coimbra, Diogo Dominguini, Felipe Dal-Pizzol, Tatiana Barichello, Maria José Alves Rocha

Faculty, Staff and Student Publications

Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. …

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, …

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. …

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 …

Fgf21 Acts In The Brain To Drive Macronutrient-Specific Changes In Behavioral Motivation And Brain Reward Signaling, Md Shahjalal H. Khan, Sora Q. Kim, Robert C. Ross, Florina Corpodean, Redin A. Spann, Diana A. Albarado, Sun O. Fernandez-Kim, Blaise Clarke, Hans Rudolf Berthoud, Heike Münzberg, David H. Mcdougal, Yanlin He, Sangho Yu, Vance L. Albaugh, Paul L. Soto, Christopher D. Morrison

School of Medicine Faculty Publications

Objective: Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. Methods and Results: In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. When the number of responses required to access protein reward varied, protein-restricted mice exhibited higher operant responses at moderate to high response requirements. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor …

Endovascular Treatment Of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score, Milagros Galecio-Castillo, Mudassir Farooqui, Waldo R Guerrero, Marc Ribo, Ameer E Hassan, Mouhammad A Jumaa, Afshin A Divani, Michael G Abraham, Nils H Petersen, Johanna T Fifi, Amer Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Guillermo Linares, Nazli Janjua, Jazba Soomro, Darko Quispe-Orozco, Marta Olivé-Gadea, Wondewossen G Tekle, Syed F Zaidi, Sara Y Sabbagh, Tiffany Barkley, Ayush Prasad, Reade A De Leacy, Mohamad Abdalkader, Sergio Salazar-Marioni, Weston Gordon, Charoskhon Turabova, Aaron Rodriguez-Calienes, Mahmoud Dibas, Maxim Mokin, Dileep R Yavagal, Albert J Yoo, Amrou Sarraj, Tudor G Jovin, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background: Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large-vessel occlusion with tandem lesions, stratified by baseline ASPECTS.

Methods and results: We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy < 24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0-5) and high (6-10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90-day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c-3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90-day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P=0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P=0.014). Additional significant differences were found in mRS shift, …

Efficacy Of High-Definition Transcranial Alternating Current Stimulation (Hd-Tacs) At The M1 Hotspot Versus C3 Site In Modulating Corticospinal Tract Excitability, Hao Meng, Michael Houston, Nicholas Dias, Chen Guo, Gerard Francisco, Yingchun Zhang, Sheng Li

Faculty, Staff and Student Publications

Previous studies have shown that beta-band transcranial alternating current stimulation (tACS) applied at the M1 hotspot can modulate corticospinal excitability. However, it remains controversial whether tACS can influence motor unit activities at the spinal cord level. This study aims to compare the efficacy of applying tACS over the hotspot versus the conventional C3 site on motor unit activities and subsequent behavioral changes. This study used a randomized crossover trial design, where fifteen healthy participants performed a paced ball-squeezing exercise while receiving high-definition tACS (HD-tACS) at 21 Hz and 2 mA for 20 min. HD-tACS targeted either the flexor digitorum superficialis …

Discovery Of Highly Potent And Alk2/Alk1 Selective Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Ravikumar Jimmidi, Diana Monsivais, Hai Minh Ta, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse …