Medicine and Health Sciences Commons^™

Transcription-Replication Collisions Trigger High-Fidelity Replication Reset, Matthew B Cooke, Kobie T Welch, Laura Deus Ramirez, Katelin M Hagstrom, Alice X Wen, Jennifer A Halliday, Susan M Rosenberg, Christophe Herman

Faculty, Staff and Students Publications

Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled …

Multimodal Cardiac Imaging Of Immune-Mediated Complications Post Heart Transplantation: A Contemporary Review, Bruno Bezerra Lima, Tam T Doan, Atilla Feher, James C Wilkinson, Marvin W Kronenberg, Chloe Carr, Malek Nayfeh, Tania Ruiz, Luke L Laws, Melissa Lou Silva, John A Wells, Leandro Slipczuk, Emily T Lippincott, John J Carr, Kaushik Amancherla, Cameron Henry, David Parra, Kelly Schlendorf, Quinn S Wells, Sean G Hughes, Jonathan Soslow

Faculty, Staff and Students Publications

Heart transplantation significantly enhances survival and quality of life for patients with end-stage heart failure. Despite advances in surgical and postoperative care, immune-mediated complications, acute graft rejection and cardiac allograft vasculopathy (CAV), remain major barriers to long-term success. Acute rejection predominantly affects early posttransplant survival, whereas CAV becomes a leading cause of mortality in later years. The gold standards for diagnosis, endomyocardial biopsy for rejection and coronary angiography for CAV, are invasive and imperfect. Noninvasive multimodality imaging is increasingly used to complement or, in selected scenarios, defer invasive testing. Echocardiography with strain detects early myocardial dysfunction when ejection fraction is …

Waiting Room And Hallway Care For Older Adults: A Qualitative Study With Emergency Nurses And Technicians, Sarah J Nessen, Ari B Friedman, Annika R Bhananker, K Jane Muir, Anita N Chary

Faculty, Staff and Students Publications

Background: Emergency Department (ED) crowding places older ED patients at risk for adverse outcomes. Crowding often necessitates ED waiting room and hallway care, but there has been limited research on approaches to care for older adults in these settings. Frontline clinician insights can inform best practices for older adults in the context of the ongoing ED crowding crisis. Our objective was to describe the experiences of emergency nurses and technicians in providing waiting room and hallway care for older adults.

Methods: This qualitative study used individual, semi-structured interviews with a purposive sample of 20 ED nurses and technicians at a …

Investigating The Neuronal Role Of The Proteasomal Atpase Subunit Gene Psmc5 In Neurodevelopmental Proteasomopathies, Sébastien Küry, Janelle E Stanton, Geeske M Van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most, Tianyun Wang, Jonas J Papendorf, Charlotte De Konink, Wallid Deb, Virginie Vignard, Maja Studencka-Turski, Thomas Besnard, Anna M Hajdukowicz, Franziska G Thiel, Sophie Wolfgramm, Laëtitia Florenceau, Silvestre Cuinat, Sylvain Marsac, Yann Verrès, Audrey Dangoumau, Léa Poirier, Ingrid M Wentzensen, Annabelle Tuttle, Cara Forster, Johanna Striesow, Richard Golnik, Damara Ortiz, Laura Jenkins, Jill A Rosenfeld, Alban Ziegler, Clara Houdayer, Dominique Bonneau, Erin Torti, Amber Begtrup, Kristin G Monaghan, Sureni V Mullegama, Catharina M L Nienke Volker-Touw, Koen L I Van Gassen, Renske Oegema, Mirjam S De Pagter, Katharina Steindl, Anita Rauch, Ivan Ivanovski, Kimberly Mcdonald, Emily Boothe, Andrew Dauber, Janice Baker, Noelle Andrea V Fabie, Raphael A Bernier, Tychele N Turner, Siddharth Srivastava, Kira A Dies, Lindsay C Swanson, Carrie Costin, Alali Abdulrazak, Rebekah K Jobling, John Pappas, Rachel Rabin, Dmitriy Niyazov, Anne Chun-Hui Tsai, Karen Kovak, David B Beck, May Christine V Malicdan, David R Adams, Lynne Wolfe, Rebecca D Ganetzky, Colleen C Muraresku, Davit Babikyan, Zdeněk Sedláček, Miroslava Hančárová, Andrew T Timberlake, Hind Al Saif, Berkley Nestler, Kayla King, M J Hajianpour, Gregory Costain, D'Arcy Prendergast, Chumei Li, David Geneviève, Antonio Vitobello, Arthur Sorlin, Christophe Philippe, Tamar Harel, Ori Toker, Ataf Sabir, Derek Lim, Mark J Hamilton, Lisa J Bryson, Elaine Cleary, Sacha Weber, Trevor L Hoffman, Anna M Cueto-González, Eduardo F Tizzano, David Gómez-Andrés, Marta Codina-Solà, Athina Ververi, Efterpi Pavlidou, Alexandros Lambropoulos, Kyriakos Garganis, Marlène Rio, Jonathan Levy, Sarah J Langas, Anne M Mcrae, Mathieu K Lessard, Maria Daniela D'Agostino, Isabelle De Bie, Meret Wegler, Rami Abou Jamra, Susanne B Kamphausen, Viktoria Bothe, Lorraine Potocki, Eric Olinger, Yves Sznajer, Elsa Wiame, Michelle L Thompson, Molly C Schroeder, Catherine Gooch, Raphael A Smith, Arti Pandya, Larissa M Busch, Uwe Völker, Elke Hammer, Kristian Wende, Benjamin Cogné, Bertrand Isidor, Jens Meiler, Clémentine Ripoll, Stéphanie Bigou, Frédéric Laumonnier, Peter W Hildebrand, Evan E Eichler, Kirsty Mcwalter, Peter M Krawitz, Florence Roux-Dalvai, Ype Elgersma, Julien Marcoux, Marie-Pierre Bousquet, Arnaud Droit, Jeremie Poschmann, Andreas M Grabrucker, Francois V Bolduc, Stéphane Bézieau, Frédéric Ebstein, Elke Krüger

Faculty, Staff and Students Publications

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor …

Leaping Between Branches: Hybridisation And The Tangled Evolutionary History Of True Lemurs, Giacomo Mercuri, Giovanni Merici, Kyle Kai-How Farh, Lukas F K Kuderna, Jeffrey Rogers, Tomàs Marques-Bonet, Giuseppe Donati, Riccardo Percudani, Cristian Capelli

Faculty, Staff and Students Publications

The true lemurs (genus Eulemur) are a genetically diverse and spatially widespread group of species inhabiting most of Madagascar's forests. Including 12 recognized species, the genus can be divided into four major evolutionary groups: E. rubriventer, E. mongoz, the Brown Lemur Species Complex (BLSC), and the coronatus-macaco-flavifrons complex (CMFC), although monophyly for the CMFC is not always supported. Recent genome-based studies highlighted topological and chronological differences between nuclear and mitochondrial phylogenies of true lemurs, which could be explained by events of hybridisation. In order to reconstruct the evolutionary history of the genus, we test for gene-flow between Eulemur clades using …

Hemorrhage-Related Maternal Morbidity Of Secondary Compared To Primary Postpartum Hemorrhage, Matthew R Carroll, Sarah Tounsi, Jessica L Gerard, Susan M Leong-Kee, Laurie S Swaim, Mark A Turrentine

Faculty, Staff and Students Publications

Objectives: To compare a composite hemorrhage-related maternal morbidity in individuals with secondary to primary postpartum hemorrhage and treatment interventions utilized.

Methods: A retrospective case-control study of deliveries complicated by secondary postpartum hemorrhage was performed at a tertiary care center. To estimate a clinically relevant increase of 50 % in the composite maternal hemorrhage-related maternal morbidity (35-53 % absolute increase) in individuals with secondary postpartum hemorrhage, a correlation coefficient of 0.2, at an 80 % power with a p < 0.05 with a two-sided test would require 95 individuals with secondary postpartum hemorrhage be matched to 95 individuals with a primary postpartum hemorrhage. Logistic regression analysis was used to evaluate the outcome of the composite of hemorrhage-related maternal morbidity.

Results: From January 2018 through December 2022, 33,026 deliveries occurred, and 94 individuals were identified that were admitted with secondary postpartum hemorrhage, …

Hemolysis Detection Using The Gem 7000 At The Point Of Care In A Pediatric Hospital Setting: Does It Affect Outcomes?, Ridwan B Ibrahim, Nazmin Bithi, Charlene Hernandez, Hanna Uhrova, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

No abstract provided.

An Analysis Of Diagnostic Metabolomic Profiles Associated With Hepatotoxicity During Childhood All Induction Therapy, Emily J Mason, Anna M Crain, Michael E Scheurer, Philip J Lupo, Karen R Rabin, Olga A Taylor, Marley Roberts, John P Woodhouse, Ashley Chavana, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, M Monica Gramatges, Joanna S Yi, Sandi L Pruitt, M Brooke Bernhardt, Hong Zhu, Steven D Mittelman, Van Huynh, Etan Orgel, Jeremy M Schraw, Austin L Brown

Faculty, Staff and Students Publications

Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children’s Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body …

Turning Patients' Open-Ended Narratives Of Chronic Pain Into Quantitative Measures: Natural Language Processing Study, Raquel Norel, Jennifer Gewandter, Zhengwu Zhang, Anika Tahsin, Chadi G Abdallah, John Markman, Zhiyao Duan, Guillermo Cecchi, Paul Geha

Faculty, Staff and Students Publications

Background: Subjective report of pain remains the gold standard for assessing symptoms in patients with chronic pain and their response to analgesics. This subjectivity underscores the importance of understanding patients' personal narratives, as they offer an accurate representation of the illness experience.

Objective: In this pilot study involving 20 patients with chronic low back pain (CLBP), we applied emerging tools from natural language processing (NLP) to derive quantitative measures that captured patients' pain narratives.

Methods: Patients' narratives were collected during recorded semistructured interviews in which they spoke about their lives in general and their experiences with CLBP. Given that NLP …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

A Contemporary Review On Heart Failure With Improved Ejection Fraction, Allison Weiss, Ambre Flowers, Scott D Eisenberg, Lingling Wu, Mario Rodriguez, Muzamil Khawaja, Errol Moras, Carl J Lavie, Gregg C Fonarow, W H Wilson Tang, Biykem Bozkurt, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Heart failure is a complex condition caused by various etiologies that reduce cardiac output or increase cardiac pressures. It is classified by left ventricular ejection fraction, a key prognostic factor. New therapies, devices, and better management of secondary causes have improved outcomes. A recently identified group-those with heart failure and improved ejection fraction-shows better prognosis. This review explores its definition, causes, clinical significance, and management strategies.

Profiling Tumour-Infiltrating Immune Cells In A Large Paediatric Medulloblastoma Cohort: A Retrospective Analysis, Mingze Chen, Xiangjun Shi, Yi Wang, Jiao Zhang, Jirong Guo, Xiuchen Guan, Yu Sun, Wenhao Wu, Chunde Li, Yongji Tian, Yunwei Ou, Tian Li, Kai Jiang, Michael D Taylor, Xuebin Liao, Liwei Zhang, Tao Sun

Faculty, Staff and Students Publications

Background: Tumour-infiltrating immune cells exert both pro-tumour and anti-tumour effects on intracranial tumours. In this study, we investigated the prognostic value of various infiltrating immune cells in medulloblastoma (MB) within a large cohort.

Methods: We employed multiplex immunofluorescent (mIF) staining of tissue microarrays to assess the densities of T cells, B cells, NK cells, macrophages, and immune checkpoints in tumour samples from 249 primary paediatric patients with primary MB. Overall survival (OS) analysis, progression-free survival (PFS), and Cox regression analyses were utilised to explore potential relationships between immune cell densities and survival outcomes. Subsequently, multivariate Cox regression was validated using …

Bilateral Concomitant Infection Of Cytomegalovirus And Varicella-Zoster Virus Retinitis In An Immunocompromised Adult, Henry C Skrehot, Amer Alsoudi, Daniel Olson, Nhon Le, Asad Loya, Tahira Scholle

Faculty, Staff and Students Publications

Purpose: To report a novel case of bilateral concomitant cytomegalovirus (CMV) retinitis and acute retinal necrosis (ARN) due to varicella-zoster virus (VZV) in an immunocompromised adult.

Methods: A case report was evaluated.

Results: A 36-year-old immunocompromised man presented with acute painful vision loss in the left eye. On initial presentation, uncorrected distance visual acuity was 20/20 in the right eye and counting fingers at 3 feet (≈1 m), which deteriorated to no light perception (NLP) in the left eye. Fundus examination showed necrotizing retinitis in both eyes, with features of both CMV retinitis and ARN. One week after initiation of …

The Effect Of Uterine Entry Technique On Chorioamniotic Membrane Separation In Fetoscopic Laser Photocoagulation For Twin-To-Twin Transfusion Syndrome: Protocol For A Randomized Controlled Trial, Brian A Burnett, Jessian L Munoz, Rebecca M Johnson, Christian M Parobek, Luis E Delgadillo Chabolla, Cara Buskmiller, Roopali V Donepudi, Magdalena Sanz Cortes, Michael A Belfort, Ahmed A Nassr

Faculty, Staff and Students Publications

Background: Chorioamniotic membrane separation (CAS) is a recognized complication of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS), associated with increased risks of preterm prelabor rupture of membranes (PPROM) and preterm birth (PTB). Although CAS is well described, its incidence and relationship to specific surgical techniques, particularly the method of uterine entry, are not well defined in the published literature. No randomized trials have evaluated whether entry technique influences the risk of CAS.

Methods: We present the protocol for a randomized controlled trial comparing sharp-trocar and Seldinger uterine entry techniques for FLP in TTTS diagnosed between 16 + 0 …

Deletion Of Fibro-Adipogenic Progenitors-Specific Follistatin Impairs Muscle Function And Accelerates Skeletal Muscle Atrophy In Obese Mice, Muhammad Rahil Aslam, Muhammad Bilal, Allah Nawaz, Tomonobu Kado, Shinya Abe, Nguyen Quynh Phuong, Memoona, Sana Khalid, Le Duc Anh, Ayumi Nishimura, Yoshiyuki Watanabe, Yoshiko Igarashi, Naeem Iqbal, Maki Yokoyama, Yasuhiro Onogi, Kennichi Hirabayashi, Hiroyuki Miwa, Takumi Era, Martin M Matzuk, Seiji Yamamoto, Koichi Ikuta, Isao Usui, Kohta Kobayashi, Toshihiko Satake, Masaru Kato, Shiho Fujisaka, Kazuyuki Tobe

Faculty, Staff and Students Publications

Background: Follistatin is a potent regulator of various TGF-β superfamily members, including myostatin (MSTN) and activin A. Previous studies have shown that follistatin is crucial in enhancing myogenesis during acute muscle injury. The mechanism by which fibro-adipogenic progenitors (FAPs)-specific follistatin influences muscle homeostasis in obese mice remains unknown. Therefore, we investigated the physiological role of follistatin in PDGFRα-positive FAPs in the regulation of muscle homeostasis and exercise in obese mice.

Methods: A PDGFRα-specific follistatin knockout (follistatin KO) mouse model was generated using PDGFRα-GFP-CreERT2 (PDGFRα-GCE) and follistatinflox/flox mice. These mice were fed a 60% high-fat diet (HFD) for 20 weeks, followed …

Alteration Of Gut Microbial Ecology By The Direct Activation Of The Brain: Inverse Gut-Microbiome-Brain Dynamics, I-Ching Wang, Jessica L Swanson, Jillian L Waters, Mikhail Y Kochukov, Shelly A Buffington, Sean W Dooling, Benjamin R Arenkiel, Mauro Costa-Mattioli

Faculty, Staff and Students Publications

The gut-microbiome-brain axis is a bidirectional communication system influencing host physiology and overall fitness. While "bottom-up" effects-where gut microbes influence brain function and behavior-are well established, direct evidence for "top-down" modulation-where the brain shapes the gut microbial ecology-remains elusive. Here, we show that the selective expression of the bacterial ion channel mNaChBac in glutamatergic lateral habenula (LHb) neurons increases their bursting activity and leads to endophentypes associated with depression. Importantly, this chronic activation leads to changes in the gut microbiome composition over time, as reflected by shifts in alpha-diversity and alterations in specific microbial taxa. These findings provide direct evidence …

Diras3-Derived Cyclic Peptides Disrupt Kras-Raf Interaction And Kras Nanoclustering, Suppressing Kras-Driven Pancreatic And Ovarian Tumors, Joshua P Gray, Gamze Bildik, Ha-Neul Kim, Margie N Sutton, Jing Wang, Amarachi O Osuji, Nefeli Batistatou, Hailing Yang, Weiqun Mao, Zhi Tan, Geneviève M C Gasmi-Seabrook, Junchen Liu, John F Hancock, Christopher B Marshall, Joshua A Kritzer, Mitsuhiko Ikura, Robert C Bast, Steven W Millward, Zhen Lu

Faculty, Staff and Students Publications

Mutations in KRAS drive 88% of pancreatic ductal adenocarcinomas (PDAC) and up to 40% of low-grade serous ovarian cancers (LGSOC), making KRAS a long-standing therapeutic target. We previously showed that DIRAS3 binds RAS, forming heterodimers that disrupt RAS clustering and downstream MAPK signaling. Building on this, we developed conformationally constrained DIRAS3-derived peptides using two cyclization strategies and characterized them by NMR and biolayer interferometry. These cyclic peptides attenuate the interaction between KRAS and the BRAF RAS-binding domain, penetrate cells efficiently, and inhibit KRAS nanoclustering on the inner leaflet of the plasma membrane. Functionally, they reduce cell viability and suppress PDAC …

Identifying Compounds To Treat Opiate Use Disorder By Leveraging Multi-Omic Data Integration And Multiple Drug Repurposing Databases, Jeran K Stratford, Megan Ulmer Carnes, Caryn Willis, Melyssa S Minto, Logain Elnimeiry, Ravi Mathur, Matthew Schu, Bryan C Quach, Javan Carter, Tracy Nolen, Nathan Vandergrift, Thomas R Kosten, Eric Otto Johnson, Bradley T Webb

Faculty, Staff and Students Publications

Genes influencing opioid use disorder (OUD) biology have been identified via genome-wide association studies (GWAS), gene expression, and network analyses. These discoveries provide opportunities to identifying existing compounds targeting these genes for drug repurposing studies. However, systematically integrating discovery results and identifying relevant available pharmacotherapies for OUD repurposing studies is challenging. To address this, we've constructed a framework that uses existing results and drug databases to identify candidate pharmacotherapies. For this study, two independent OUD related meta-analyses were used including a GWAS and a differential gene expression (DGE) study of post-mortem human brain. Protein-Protein Interaction (PPI) sub-networks enriched for GWAS …

Single Cell Long Read Whole Genome Sequencing Reveals Somatic Transposon Activity In Human Brain, Michal B Izydorczyk, Ester Kalef-Ezra, Dominic W Horner, Xinchang Zheng, Nadine Holmes, Marco Toffoli, Zeliha Sahin, Yi Han, Heer H Mehta, Sonja W Scholz, Clifton L Dalgard, Donna M Muzny, Adam Ameur, Fritz J Sedlazeck, Christos Proukakis

Faculty, Staff and Students Publications

The advent of single cell DNA sequencing revealed astonishing dynamics of genomic variability, but failed at characterizing smaller to mid size variants that on the germline level have a profound impact. In this work we discover previously uncharacterized genomic dynamics in 18 cells from three human brains utilizing single cell long-read whole genome sequencing. This provides key insights into the dynamic of the genomes of individual cells and further highlights brain specific activity of transposable elements, but requires validation in larger studies.

Retinol Tracing Within Murine Neural Retina Reveals Cell Type-Specific Retinol Transport And Distribution, Zachary J Engfer, Grazyna Palczewska, Samuel W Du, Jianye Zhang, Zhiqian Dong, Carolline Rodrigues Menezes, Jun Wang, Jianming Shao, Budd A Tucker, Robert F Mullins, Rui Chen, Philip D Kiser, Krzysztof Palczewski

Faculty, Staff and Students Publications

11-cis-Retinal is essential for light perception in mammalian photoreceptors (PRs), and aberrations in retinoid transformations cause severe retinal diseases. Understanding these processes is crucial for combating blinding diseases. The visual cycle, operating within PRs and the retinal pigment epithelium (RPE), regenerates 11-cis-retinal to sustain light sensitivity. Retinoids are also present in Müller glia (MG), hypothesized to supply 11-cis-retinol to cone PRs and retinal ganglion cells (RGCs). To trace retinoid movement through retinal cell types, we used cell-specific knock-in of lecithin:retinol acyltransferase (LRAT), which converts retinols into stable retinyl esters (REs). Ectopic LRAT expression in murine PRs, MG, and RGCs resulted …

Be Faster Community Of Practice To Increase Rapid Initiation Of Antiretroviral Therapy In Houston, Texas: A Pre-Post Intervention Study, Naomi Sequeira, Bich N Dang, Melanie Goebel, Monisha Arya, Avishek Ghosh-Hajra, Kathryn Fergus, Shital M Patel

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy of the Ending the HIV Epidemic (EHE) initiative. The Baylor College of Medicine Extension for Community Healthcare Outcomes (ECHO) Facilitating Antiretroviral Start Earlier (BE FASTER) program was developed to address this call-to-action. The program uses the ProjectECHO tele-mentoring model as an implementation tool in Harris County, a priority EHE jurisdiction. The authors present results on the acceptability and feasibility of the BE FASTER program.

Methods: Multidisciplinary health professionals from 5 Ryan White Part A funded agencies formed the community of practice. The BE FASTER program included 9 monthly …

Improved Technical Outcomes With Converting Thrombectomy Techniques After Failed First Pass Recanalization, Hidetoshi Matsukawa, Charles Matouk, Kazutaka Uchida, Sami Al Kasab, Mohammad-Mahdi Sowlat, Sameh Samir Elawady, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Q Wolfe, Ansaar T Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Adam S Arthur, Hugo Cuellar, Brain M Howard, Daniele G Romano, Omar Tanweer, Justin R Mascitelli, Isabel Fragata, Adam Polifka, Joshua W Osbun, Roberto Javier Crosa, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Richard Williamson, Pedro Navia, Peter Kan, Reade Andrew De Leacy, Shakeel A Chowdhry, Mohamad Ezzeldin, Alejandro M Spiotta, Shinichi Yoshimura, Ali M Alawieh

Faculty, Staff and Students Publications

Background: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes.

Methods: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique …

Elastic Cytomatrix Dynamics Influences Metabolic Rate And Tumor Microenvironment Formation, Tattym E Shaiken, Tulendy T Nurkenov, Meruyert S Kurmanbayeva, David Y Graham

Faculty, Staff and Students Publications

In healthy cells, the cytomatrix mechanics utilize mitochondrial respiration to control cytosolic motion and fine-tune the chemical processes. In cancer, the cytosolic motion is energized by glycolytic fermentation (the Warburg effect), which provides additional energy to supply the needs of the cytomatrix. Here, we describe the physical and chemical processes of the integrated and cooperative cytomatrix cytoarchitecture, in which structure and function are inseparable. The extracellular matrix is interconnected with the intracellular cytomatrix and functions as two integrated elastic solid phases. This finding led us to propose mechanisms of tumor microenvironment formation resulting from the mutational burden, in which altered …

Apathy Self-Awareness And Its Neural Correlates In Parkinson’S Disease, Hannah Conn, Hideo Suzuki, Zekai Jin, Ana Marin, Xi Zhu, Seonjoo Lee, Edward Huey, Ratko Radakovic, Sarah R Heilbronner, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy is a prevalent non-motor symptom in Parkinson's disease (PD) that negatively impacts quality of life. Impaired self-awareness of apathy (ISA-a) further impacts patient care by limiting engagement. While apathy has been associated with reduced fronto-striatal functional connectivity (FC), the neural basis of ISA-a remains unclear. We examined ISA-a in 52 individuals and the neural basis of ISA-a in 35 individuals with PD using a dimensional approach (i.e., initiation, executive, and emotional apathy) and resting-state fMRI (3T scanner). Apathetic PD patients (42%) showed poorer self-awareness than non-apathetic peers. Apathetic PD patients showed a trend towards reduced FC between the left …

Describing The Determinants Of Fluid Prescribing And Fluid Balance Optimization In The Pediatric Intensive Care Unit: A Qualitative Study At A Community Hospital, Salvador Roland Maffei, Graciela Sanabria, Matthew Pesek, Ayse Akcan-Arikan, Satid Thammasitboon, Patrick G Lyons

Faculty, Staff and Students Publications

Background: Critically ill children tend to receive fluid volumes exceeding physiologic requirements despite evidence demonstrating harm with increasing net positive fluid balance. However, interventions aimed at optimizing fluid balance have yet to demonstrate significant clinical benefit, likely because there are multiple drivers of this complex problem. In this study, we used qualitative inquiry to describe the current practice at a community pediatric intensive care unit and discover potential barriers and facilitators to clinical practice change.

Methods: We designed a semi-structured interview guide informed by the consolidated framework in implementation research (CFIR) and conducted interviews with attending physicians, dietitians, nurses, nurse …

Family Caregivers' Perspectives On Challenges And Support Needs In Hospital-Based Palliative Care For Persons Living With Dementia, Jung Kwak, Anita Chary, Sarah Stayer, Kwaku Duah Oppong, Sumin Yoon, Snehal Patel, Elizabeth A Kvale

Faculty, Staff and Students Publications

Palliative care needs of hospitalized persons living with dementia (PLWD) and their family caregivers remain poorly understood. This mixed-methods study explored caregivers' perspectives on challenges and support needs when hospitalized PLWD received specialist palliative care consultations. Thirty-two caregivers were recruited from two hospitals; 18 completed interviews and surveys, and 14 completed surveys only. Participants were racially and ethnically diverse (19% Black or African American, 34% Latino or Hispanic). Most identified as women (65%) and adult children (56%). Commonly reported challenges included managing health issues (59%), emotional distress (56%), and decision-making (47%). Thematic analysis of interviews revealed three themes: the value …

Comparing Diagnostic Tools For Heart Failure With Preserved Ejection Fraction Across Community And Clinical Cohorts, Luca Monzo, Olivier Huttin, Biykem Bozkurt, Kévin Duarte, Cecilia Linde, Lars H Lund, Camilla Hage, Erwan Donal, Martin Magnusson, Peter Nilsson, Margret Leosdottir, Erwan Bozec, Guillaume Baudry, Faiez Zannad, Nicolas Girerd

Faculty, Staff and Students Publications

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, particularly in older adults. While the Heart Failure Association (HFA)-PEFF and H2FPEF Scores offer structured diagnostic approaches, their clinical utility is still debated. This study aims to compare the diagnostic accuracy of HFpEF Scores versus inclusion criteria used in sodium-glucose cotransporter-2 inhibitors (SGLT2i) trials, age-adjusted N-terminal pro B-type natriuretic peptide (NT-proBNP) thresholds and the universal definition of heart failure (HF).

Methods: Diagnostic tools were assessed using sex-weighted and age-weighted propensity score adjustment in individuals aged 60-80 years from two established HFpEF cohorts (MEtabolic Road to DIAstolic Heart Failure (MEDIA), …

Disinhibited Behavior Associated With Rapid Clinical Response To Deep Brain Stimulation For Obsessive-Compulsive Disorder: Illustrative Cases, Sarah S Soubra, Tommy B Liu, Zain U Naqvi, Thomas Hamre, Danika L Paulo, Kalman A Katlowitz, Nisha Giridharan, Katie Van Arsdel, Jonathan H Bentley, Kasra A Mansourian, Davin Devara, Eric A Storch, Sarah R Heilbronner, Sameer A Sheth, Wayne Goodman, Nicole R Provenza

Faculty, Staff and Students Publications

Background: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) can alleviate symptoms of obsessive-compulsive disorder (OCD) refractory to conventional therapies. Overstimulation, however, can elicit pathological behaviors marked by disinhibition and recklessness.

Observations: Two patients with OCD underwent DBS of the VC/VS region and met responder status within 1 month of stimulation onset, as evidenced by a ≥ 35% reduction in their Yale-Brown Obsessive Compulsive Scale score. Notably, both patients exhibited signs of disinhibited behavior soon after DBS activation, including gambling, sleep disruption, and interpersonal relationship volatility. Through careful management, responder status persisted stably beyond the transient period of …

Application Of Freezetb, A Targeted Nanopore Sequencing Assay, For Identification Of Drug Resistance And Lineages Among Pulmonary Tuberculosis Cases In Alaska, Bryce Inman, Jeremy Butler, Soren George-Nichol, Ganna Kovalenko, Theresa Savidge, Yvette Vergnetti, Catherine Pongratz, Elizabeth Bee, Andrew R Dinardo, Alexander Kay, Anna Mandalakas, Eric Bortz, Tara E Ness

Faculty, Staff and Students Publications

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in Mycobacterium tuberculosis using targeted next-generation sequencing (tNGS). FreezeTB, a Fast, Reliable, Economical Evaluation tool to Zap Endemic Tuberculosis, amplifies 22 gene loci associated with resistance to 16 anti-tuberculosis drugs. M. tuberculosis isolates from Alaska …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …