Medicine and Health Sciences Commons^™

Classification Of Gck-Mody In A Child With Mild Hyperglycemia And Islet Autoantibody Positivity: A Diagnostic Challenge, Aman N Yarlagadda, Maria J Redondo, Toni I Pollin, Mustafa Tosur, Colleen O Jodarski, Jennifer J Bell

Faculty, Staff and Students Publications

We report a 9-year-old female who presented with mild, persistent hyperglycemia, with hemoglobin A1c and oral glucose tolerance test results in the prediabetes range, relatively preserved C-peptide, and mildly positive glutamate decarboxylase 65 autoantibody levels. A strong family history of lean, noninsulin-dependent diabetes suggested a possible monogenic cause. Genetic testing with a 28-gene maturity-onset diabetes of the young (MODY) panel identified a heterozygous variant of uncertain significance in GCK (NM_000162.5:c.179C>T [p.Thr60Ile]). Following review by the ClinGen Monogenic Diabetes Variant Curation Expert Panel, the GCK variant was reclassified as pathogenic, confirming a diagnosis of glucokinase (GCK)-MODY/GCK-hyperglycemia, a stable …

Anterior Cutaneous Nerve Entrapment Syndrome From Glucagon-Like Peptide-1 Receptor Agonist Injection, Neha Singh, Elisa Chaparro, Jordan Michael Shapiro, Emanuel Narcis Husu

Faculty, Staff and Students Publications

Anterior cutaneous nerve entrapment syndrome (ACNES) is an underdiagnosed cause of abdominal pain. We report the first documented ACNES case following subcutaneous administration of glucagon-like peptide-1 receptor agonist. A 44-year-old man developed focal, neuropathic abdominal pain coinciding with initiation of tirzepatide injections. Clinical examination confirmed ACNES diagnosis, and pain improved after relocating injections away from the abdomen and initiating multimodal pharmacotherapy. This case emphasizes the need to consider ACNES in patients endorsing focal abdominal pain with concurrent use of glucagon-like peptide-1 therapy and highlights injection site modification as a simple, effective management strategy while exercising self-restraint with respect to workup.

A Trans-Omics Gene-Smoking Interaction Study Of Lung Cancer Based On Consortium Data, Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller, Zhibin Hu, Hongbing Shen, Rayjean J Hung, Christopher I Amos, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang

Faculty, Staff and Students Publications

Rationale: Genetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

Objectives: To identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

Methods: We conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the …

Malaria In Children At 9 Us Hospitals: 2016-2023, Sesh Alexander Sundararaman, Brianne Roper, Amy K F Davis, Karen L Hanze Villavicencio, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Ziyi Wang, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Objectives: This study set out to describe imported pediatric malaria in the United States over an 8-year period, including patient demographics, clinical outcomes, and risk factors for severe disease.

Methods: A retrospective descriptive study of pediatric patients treated for malaria at 9 hospitals in the United States from 2016 to 2023 was conducted to analyze patient demographics, clinical outcomes, and risk factors for severe malaria.

Results: A total of 171 children were treated across the 9 US hospitals included in this study from 2016 to 2023. Most patients had traveled to West Africa to visit friends and relatives. Fever was …

Identification Of A Persistent Ascaris-Derived Kalirin Epitope Associated With Chronic T Cell Activation In The Lung, Yifan Wu, Leroy Versteeg, Meng-Chih Wu, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis remains a dominant global health burden due to its vast prevalence and associated morbidity. The obligatory migration of Ascaris larvae through pulmonary tissue triggers intense type-2 inflammation which typically presents as acute allergic airway disease. Even after the parasite is eliminated, a single episode of larval migration can result in chronic lung damage and dysfunction, which may be driven by the long-term retention of helminth antigens in macrophages. However, the molecular identity of these retained antigens, and the mechanisms by which they sustain chronic T cell responses, remain unknown. In this study, we utilized immunopeptidomics to identify a retained …

Validation Of The Immune-Mediated Colitis Endoscopic Score Using A Retrospective Cohort Of Patients With Immune-Mediated Colitis, Malek Shatila, Carolina Colli Cruz, Krishnavathana Varatharajalu, Andres Caleb Urias Rivera, Kian Abdul-Baki, Kei Takigawa, Tanvi Gupta, Elliot Baerman, Linfeng Lu, Irene Jeong-Ah Lee, Hamza Salim, Raakhi Menon, Andrew Sullivan, Varun Vemulapalli, Cristina Natha, Ayesha Khan, Petros Grivas, David Faleck, Michael Dougan, Anusha Shirwaiker Thomas, Yinghong Wang

Faculty, Staff and Students Publications

Background and aims: Immune-mediated colitis (IMC) is a challenging adverse effect of immune checkpoint inhibitor therapy, often leading to treatment interruption or discontinuation. Current IMC endoscopic scoring systems were adapted from those used for inflammatory bowel disease but fail to fully capture IMC. The newly proposed IMC endoscopic score (IMCES) seeks to help guide prognosis and treatment. We aimed to validate IMCES and explore its association with IMC clinical severity and outcomes.

Methods: This single-center retrospective study included patients with IMC who received immune checkpoint inhibitors and underwent endoscopic evaluation. IMCESs were calculated on the basis of 10 gross endoscopic …

Rethinking Flow: The Paradox Of Renoprotection Without Increased Renal Blood Flow In Cardiopulmonary Bypass, Shiksha Mohan, Ronald A Shaju, Sharan Misra, Titiksha Sharma, Veeraj K Sirivolu, Abhinav Rajkumar, Anthony Rodas-Camacho, Aizah Zaidi, Dhruv Dhingra, Ilma Khan, Rishav Bhattacharya, Vishal Pancholy, Shivam Banerjee, Shreyo Ghosh, Shiyi Li, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

No abstract provided.

Perinatal Mental Health Screening And Care Among Those With Pregnancy Complications, Alison N Goulding, Terri L Fletcher, Emily S Miller

Faculty, Staff and Students Publications

Perinatal mental health conditions are common and, without effective treatment, can contribute to adverse maternal and child outcomes. In the United States, mental health conditions are a leading cause of maternal morbidity and mortality, contributing to over 20% of pregnancy-related deaths. This expert review aims to assess current literature and provide recommendations regarding mental health care in high-risk patients who experience pregnancy complications. Individuals experiencing pregnancy complications are at increased risk for perinatal mental health conditions, including depression, anxiety, and post-traumatic stress disorder, as compared to those with uncomplicated pregnancies. Despite this increased disease burden, there is limited research on …

Choline Counteracts Pregnancy Undernutrition-Associated Colitis In Sheep By Restoring Microbiota Driven Bile Acid Metabolism, Weibin Wu, Peng Jiao, Yamei Gu, Huizhen Lu, Caiyun Fan, Zheng Sun, Lizhuang Hao, Shengyong Mao, Jianbo Cheng, Yanfeng Xue

Faculty, Staff and Students Publications

High-fertility sheep experience undernutrition during late gestation, which induces body metabolic disruption and intestinal inflammation. Crucially, the gut microbiota-bile acid axis is a promising intestinal inflammation target, but how choline modulates this axis in livestock enteritis is unknown. This study investigated choline's protective mechanisms against undernutrition-induced intestinal inflammation in sheep, focusing on gut microbiota and bile acid regulation. Choline consistently alleviates colitis severity, restores epithelial barrier integrity, and suppresses intestinal inflammation. These protective effects are accompanied by pronounced remodeling of the colonic microbial ecosystem, characterized by the enrichment of Clostridiales bacterium to elevate bile salt hydrolase activity and regulate bile …

Coxfa4l2 Upregulation Preserves Residual Cytochrome C Oxidase Activity In Coxfa4-Related Leigh-Like Encephalopathy, Micol Falabella, Sandra Lopez Calcerrada, Jana Aref, Jiaze Gao, William L Macken, Chiara Pizzamiglio, Renata Kabiljo, Anna Lucia Francavilla, Pauline Gaignard, Antoine Pouzet, Jonathan Levy, Giulia Barcia, Jamie K Leighton, Efstathia Chronopoulou, Germaine Pierre, Riza Köksal Özgül, Ali Dursun, Rebecca Halligan, Helen Mundy, Javeria Raza Alvi, Tipu Sultan, William James Craigen, Lisa Emrick, Jill A Rosenfeld, Gehad Elmakkawy, Jihye Kim, Joseph J Gleeson, Aboulfazl Rad, Gabriela Oprea, Maqbool Hussain, Khalil Ur Rehman, Sadia Riaz, Robert W Taylor, Vincent Procaccio, Maha S Zaki, Erika Fernandez-Vizarra, Ciro Leonardo Pierri, Michael G Hanna, Henry Houlden, Reza Maroofian, Cristina Ugalde, Jan-Willem Taanman, Robert D S Pitceathly

Faculty, Staff and Students Publications

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present …

A Comparison Between Carlin And Dna Typewriter In Crispr-Mediated Lineage Tracing, Fengshuo Liu, Xiang Zhang, Yipeng Yang

Faculty, Staff and Students Publications

Background: CARLIN and DNA Typewriter are two major breakthroughs in CRISPR-based lineage tracing technology. It is essential to understand the potential and performance of these methods in lineage tracing, which provides important guidance on experimental design.

Results: In this study, we systematically compare these two strategies using a unified stochastic simulation framework with known ground-truth lineages. By explicitly modeling CRISPR editing dynamics, barcode evolution, and cell division processes, the framework enables quantitative benchmarking of lineage reconstruction accuracy across diverse experimental parameter regimes. Both methods are evaluated using multiple accuracy metrics, including Robinson-Foulds accuracy and triplet accuracy, allowing a comprehensive assessment …

Correction: Misregulated Alternative Splicing In Endometriosis: A Role For Aberrant Mrna Variants In Endometriotic Cell Growth, Venkata Naga Goutham Davuluri, Michelle Dias, Roxanna Llinas, Neha Kamath, Pooja Popli, Shannon M Hawkins, Chandrakant Tayade, Elise T Courtois, Hari Krishna Yalamanchili, Ramakrishna Kommagani

Faculty, Staff and Students Publications

This corrects the article "Misregulated alternative splicing in endometriosis: a role for aberrant mRNA variants in endometriotic cell growth", 149.

Toxitarget: A Multi-Omics Database For Toxicant-Responsive Molecular Targets, Ravindra Kumar, Tianyi Fu, Prashant Kumar Kuntala, Benpeng Miao, Shuhua Fu, Daofeng Li, Frederick L Tyson, Marisa S Bartolomei, Cheryl L Walker, Ting Wang, Bo A Zhang

Faculty, Staff and Students Publications

Environmental toxicant exposures can induce widespread alterations in both the transcriptome and epigenome of mammals, and directly contribute to the increased risk of various diseases, including cardiovascular disorders, cancer, and neurological disorders. To evaluate how early-life toxicants produce long-term impacts on the transcriptome and epigenome in mice, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 3607 multi-omics datasets from longitudinal studies in mice. The molecular changes in responding to distinct environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), …

Associations Among Pork Intake, Weight-Loss, And Diet Quality Outcomes In A Commercial Weight-Management Program, Ana M Palacios, Grace Anderson, Beate Henschel, Alexandra M Lee, Kelli M Richardson, Chelsie Parker, Stephanie L Dickinson, Jing X Kersey, David B Allison, Gary D Foster, Michelle I Cardel

Faculty, Staff and Students Publications

Background: Pork is a common source of high-quality protein. However, it is typically recommended in moderation due to its saturated fat content, especially as its role in weight management, weight-loss (WL) programs, and overall diet quality is not well understood. This study aimed to identify associations among pork intake, WL, and diet quality among adults with overweight or obesity participating in a weight management program (WMP).

Methods: This secondary analysis used data from a 6-month randomized controlled trial (NCT05648344) evaluating the effectiveness of a WMP on diet quality. Data were collected through online surveys and the Automated Self-Administered …

The 2026 Fifa World Cup: Communicable Disease Risks And Advice For Visitors To Canada, The United States, And Mexico, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Beatriz Elena Porras-Pedroza, Álvaro A Faccini-Martínez, Daniel Grisales-Nieto, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

Icam1high Neutrophils Sculpt Tumor Evolution And Metastasis Through Symbiotic Adhesion And Reverse Migration, Ling Wu, Zhan Xu, Jun Wang, Fengshuo Liu, Yunfeng Ding, Yang Gao, Siyue Wang, Jun Liu, Hilda L Chan, Weiguo Wu, Yi-Hsuan Wu, Liqun Yu, Xiaoxin Hao, Xuan Li, David G Edwards, Cher Sha, Tobie D Lee, Nan Guan, Sergio Aguirre, Luis Becerra-Dominguez, Dane Hoffman, Xiang Chen, Charlotte Helena Rivas, Xiaoyuan G Yan, Igor L Bado, Weijie Zhang, Qian Zhu, Arun Sreekumar, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Neutrophils are a prominent component of the tumor microenvironment that can have both pro- and anti-tumor functions. By analyzing neutrophils across different human cancers, we revealed an ICAM1high subset enriched in the tumor microenvironment, which were also observed in murine triple negative breast cancer (TNBC) models. ICAM1high neutrophils exhibited an enhanced capacity for cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion conferred mutual advantages to both cell types. In contrast, cancer cells with mesenchymal-like phenotypes were vulnerable to neutrophil-mediated cytotoxicity due to decreased cell adhesion and elastase resistance. These opposite effects drove tumor evolution toward a …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Pregnancy Outcomes After In Utero Exposure To Immune Checkpoint Inhibitors, Morgan Bou Zerdan, Bruna Kfoury, Eliane Aoun, Sarah Diane Hmaidan, Roni Nitecki Wilke, Jeffrey A How, Terri L Woodard, Pamela T Soliman, Laurie J Mckenzie

Faculty, Staff and Students Publications

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review.

Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases …

Unbiased Niche Labeling Maps Immune-Excluded Niche In Bone Metastasis, Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. …

A Remote Intervention To Improve Medication Nonadherence Guided By A Marker Of Risk Derived From The Electronic Health Records Of Adolescent Transplant Recipients, Eyal Shemesh, Ravinder Anand, Rachel A Annunziato, Emily M Fredericks, Jennifer Garcia, Nitika Arora Gupta, Lawrence C Kleinman, Alyssa Kriegermeier, Krupa R Mysore, Vicky L Ng, Steven J Lobritto, Shreena Patel, Emily Rothbaum Perito, Elizabeth B Rand, Rene Romero, Robert S Venick, Sarah Duncan-Park, Jeffrey Mitchell, Sarah G Anderson, Margaret L Stuber, Miguel Reyes-Múgica, George V Mazariegos, Benjamin L Shneider

Faculty, Staff and Students Publications

Improving medication adherence in adolescents who had a liver transplant (iMALT), a prospective, block-randomized, single-blind, controlled multisite study in 13 pediatric transplant centers, used the medication level variability index (MLVI) to identify nonadherent adolescents. It compared a 2-year remote behavioral telemetric intervention (TI) that focused on adherence and addressed barriers to standard of care (SOC). The primary endpoint was the composite incidence of centrally determined (3 masked pathologists) rejection, death, retransplantation, or consent withdrawal. In 148 participants (TI group, n = 72 and the SOC group, n = 76), with a mean age 15.5 years, there were twice as many …

Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu

Faculty, Staff and Students Publications

Importance: Heart failure (HF) affects more than 64 million individuals worldwide, and acute HF is associated with 1-year mortality rates of 23.6% in North America and Europe. Cardiac dyssynchrony from conduction system disease may cause HF progression, particularly in patients with left ventricular (LV) systolic dysfunction.

Observations: Electrical dyssynchrony in HF most commonly presents as left bundle-branch block and affects 20% to 30% of patients with reduced LV ejection fraction (LVEF). Cardiac resynchronization therapy, which includes biventricular pacing and conduction system pacing, restores synchronous ventricular contraction and is recommended for patients with symptomatic HF despite optimal medical therapy, LVEF of …

Targeted Suppression Of Spp1 Inhibits Tumor Invasion And Metastasis In Nrf2 Hyperactivated Cisplatin Resistant Hnscc, Mutsuki Kawabe, Sujuan Yang, Lorena I Gomez-Bolanos, Shiro Takamatsu, Sylvia Flores, Patricia D Castro, Tsung-You Tsai, Arisa Nishikawa Kaga, Kento Okamoto, Mitchell J Frederick, Vlad C Sandulache, Humam Kadara, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Background: Cisplatin remains the standard systemic therapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC), however, resistance to cisplatin continues to be a major barrier to effective treatment, particularly in tumors with NRF2 hyperactivation. Recent studies identify secreted phosphoprotein 1 (SPP1/osteopontin) as a key NRF2 target frequently overexpressed in cancers, where it drives aggressive tumor behavior, metastasis, chemoresistance, and, in some cases, immune suppression. Our recent data highlight SPP1 as one of the top 10 NRF2-upregulated genes in cisplatin-resistant HNSCC. However, its specific role in therapy resistance and metastasis in HNSCC remains unclear. Here, we investigate …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

Childcare Challenges Among Surgical Trainees And Faculty: A Single-Institution Study, Emma G Burke, Sarah Peiffer, Melissa Koci, Lindsay Dean, Kristy L Rialon, Michele Loor, Alice King

Faculty, Staff and Students Publications

Background: Previous studies have demonstrated the challenges of parenthood in surgical training and careers. However, certain aspects of childrearing for surgeons remain understudied. We aim to leftacterize the complexity and costs of childcare amongst surgical trainees and faculty.

Methods: An anonymous, self-administered survey was conducted within the Department of Surgery at a large academic medical center. Both male and female trainees and faculty were included in the analysis. Chi-square or Fisher's Exact test was performed.

Results: Forty-six respondents provided information about childcare costs, with 37% of respondents being residents or fellows. Trainees worked longer workhours (p = 0.003) than their …

Circulating Metabolites Associated With Protection Against Mycobacterium Tuberculosis Infection And Inhibition Of Mycobacterial Growth, Todia P Setiabudiawan, Lika Apriani, Julian Avila-Pacheco, Edwin Ardiansyah, Vinod Kumar, Bachti Alisjahbana, Ayesha J Verrall, Andrew R Dinardo, Agnes R Indrati, Vera P Mourits, L Charlotte J De Bree, Simone J C F M Moorlag, Clary B Clish, Leo A B Joosten, Arjan Van Laarhoven, Krista E Van Meijgaarden, Mihai G Netea, Simone A Joosten, Valerie A C M Koeken, Philip C Hill, Reinout Van Crevel

Faculty, Staff and Students Publications

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPstudys near AFMID (involved in …

The Perijunctional Zone Is A Molecularly Distinct Muscle Subdomain Altered In Duchenne Muscular Dystrophy, Seth G Haddix, Chuansheng Zhang, Yanhong Liu, Juan Oses-Prieto, Alma L Burlingame, Matthew N Rasband

Faculty, Staff and Students Publications

The neuromuscular junction (NMJ) is a well-established model for synapse development, structure, and function. Surrounding the NMJ is a narrow perijunctional zone (PJZ), enriched in muscle-specific voltage-gated sodium channels that prevent synaptic fatigue. Despite this role, the PJZ remains poorly characterized. To determine its molecular composition, we engineered mice to express the biotin ligase TurboID fused to the cell adhesion molecule neurofascin (Nfasc), and that localizes to the PJZ through ankyrin scaffolding proteins. Using proximity proteomics, we identify numerous PJZ-associated proteins, including Perilipin 4 (Plin4), that are highly enriched and clustered at the PJZ. We also perform proximity proteomics on …

Phkg2 Confers Resistance Of Escc To Cisplatin And Enhances Cxcl8-Dependent Immunosuppression To Exacerbate Tumorigenesis, Jiayan Wu, Chengrui Zhong, Haosheng Zheng, Fei Qin, Xianyu Qin, Yuzhen Zheng, Junguo Chen, Gengfeng Wang, Bozhu Jian, Zui Liu, Xingping Yang, Chao Cheng, Guolin Li, Hongying Liao

Faculty, Staff and Students Publications

Cisplatin (DDP)-based chemotherapy serves as a foundational cornerstone in the clinical management of esophageal squamous cell carcinoma (ESCC). However, intrinsic or acquired resistance to DDP persists as a significant clinical challenge, severely undermining therapeutic efficacy and contributing to unfavorable patient prognoses. Through functional screening with a CRISPR/Cas9 knockout library, transcriptomic profiling of cisplatin-resistant cell lines and clinical specimens, and in vitro/in vivo validation assays, we identified PHKG2 as a key mediator of cisplatin resistance in ESCC. Mechanistically, PHKG2-mediated cisplatin resistance is driven by the phosphorylation of IGF2BP3 at residues T225 and T306. This post-translational modification enhances IGF2BP3 phase separation, thereby …

Movement-Stabilized Three-Dimensional Optical Recordings Of Membrane Potential Changes And Calcium Dynamics In Hippocampal Ca1 Dendrites, Kevin C Gonzalez, Satoshi Terada, Asako Noguchi, George N Zakka, Cliodhna O'Toole, Giuliana Bilbao, Luke Reynolds, Anna Jász, Borbála Kertész, Zoltán Szadai, Alissa Shen, François St-Pierre, Franck Polleux, Attila Losonczy, Balázs Rózsa

Faculty, Staff and Students Publications

Local dendritic computations are thought to critically influence neuronal signaling and plasticity yet remain largely unexplored in vivo due to challenges in stably imaging small structures at ultrafast timescales. We developed a 3D real-time motion correction platform for movement-stabilized, ultrafast two-photon voltage imaging. By co-labeling CA1 pyramidal neurons with voltage and calcium indicators, we simultaneously measured somato-dendritic and electro-calcium coupling at multiple dendritic sites. We characterized isolated dendritic spikes and distance-dependent backpropagation of naturally occurring and photostimulation-evoked bursts and single spikes. We found that bursts backpropagated more reliably than single spikes, validated that somato-dendritic coupling decreases with distance from soma, …

A Review Of Robotic Vnotes Surgery: Current Applications, Advantages, And Future Directions, Daniel Y Lovell, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Over the past 500 years, the convergence of three distinct paths - vaginal surgery, laparoscopy, and robotic technologies - has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES). The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy, myomectomy, sacrocolpopexy, adnexal interventions, and oncologic operations, applicable to a wide range of diagnoses and pathologies. This approach offers patients significant benefits, including superior cosmetic outcomes, less pain, lower infection rates, and faster recovery of baseline quality of life. Surgeons benefit from improved ergonomics, better visualization, the ability to use multiple instruments, and enhanced …

Human Papillomavirus Vaccine Discourse And Sentiment On Reddit Before And After Covid-19: Mixed Methods Retrospective Cross-Sectional Study, Marcin Marciniak, Sean A Setzen, Deeya Bhattacharya, Jamie Masliah, Robin Powszok, Erich M Sturgis, Vanessa C Stubbs, Mihir K Bhayani

Faculty, Staff and Students Publications

Background: Human papillomavirus (HPV) is a sexually transmitted virus that causes various oropharyngeal and anogenital cancers. The HPV vaccine provides protection against several strains of HPV and is a key preventative tool against HPV-related cancers; however, vaccination rates remain suboptimal in the United States due to variable state mandates and misperceptions of vaccine efficacy and risks. As social media becomes an increasingly popular avenue for health discussions, platforms such as Reddit offer opportunities to understand public vaccine discourse, particularly among underrepresented groups. Furthermore, vaccine hesitancy and mistrust generally increased during the COVID-19 pandemic, potentially impacting HPV vaccination rates.

Objective: This …