Digital Commons Network^™

Ebneo Commentary: The Lakana Trial: Mass Administration Of Azithromycin To Infants In Mali Did Not Reduce Mortality, Maya I Brasher, Monika S Patil

Faculty, Staff and Students Publications

The LAKANA trial: a randomized control trial evaluating the impact of mass administration of azithromycin to infants 1 to 11 months of age in Mali showed no reduction in mortality.

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Human Exposure To Spirochete-Infected Ornithodoros Turicata In A Residential Setting In The Austin, Texas Metropolitan Area, Serhii Filatov, Bonny Mayes, Sarah M Gunter, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

A central Texas resident found an engorged Ornithodoros turicata tick attached to their ankle while at home. The tick tested positive for Borrelia turicatae, an agent for soft tick-borne relapsing fever. Three weeks earlier, the patient started experiencing febrile episodes, rash, and nausea, yet the etiological agent went undiagnosed.

Helminth-Infected Mozambican Children With Malaria Have Increased Anaemia, Cytokines And Helminth-Specific Antibodies, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejía, José Muñoz, Ruth Aguilar, Bin Zhan, Augusto Nhabomba, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Owing to their overlapping geographical distribution and the consequent occurrence of coinfections, several studies have evaluated the impact of helminth infections on malaria immune responses and clinical outcomes. However, little has been reported on how malaria coinfection affects anthelmintic responses in children harbouring worm infections. We therefore aimed to assess the impact of malaria coinfection on helminth-related clinical and immune outcomes in children. Here, we measured in plasma the levels of 30 cytokines, total IgE, and helminth-specific IgM, IgA, IgG, IgG1-4, and IgE antibodies to a panel of 11 helminth antigens by Luminex. Samples were obtained from 441 children aged …

An Examination Of Buprenorphine And Norbuprenorphine Concentrations In Inpatients Receiving Medications For Opioid Use Disorder, Michèle Haykal, Benjamin Li, Andres Avellaneda Ojeda, Roberto Sanchez, Nancy Shenoi, Asim Shah, Nidal Moukaddam

Faculty, Staff and Students Publications

Background: Interpretation of urine buprenorphine and norbuprenorphine concentrations is widely used to assess adherence during treatment for opioid use disorder. However, the relationships between dose, timing of sample collection, and metabolite ratios remain unclear, leading to potential misinterpretation in clinical practice.

Methods: Data were collected from patients on a psychiatry unit who were either inducted on or continued buprenorphine therapy and underwent urine testing for buprenorphine and its metabolite, norbuprenorphine. Urine samples were collected 16 to 786 min after the last buprenorphine dose. Norbuprenorphine-to-buprenorphine ratios were calculated. Data analysis using Python included polynomial regression and random forest models.

Results: Daily …

Blinded, Bias-Controlled Multi-Rater Evaluation Of Human-Versus-Ai Brain Metastasis Segmentation Using A Hybrid Foundation-Model Framework, Yiding Han, Enze Zhu, Mhd Hasan Ai Mekdash, Omar Awad, Piyush Pathak, Shixiao Liang, Daniel Allan Hamstra, Xizhe Zhang, Zaid Ali Siddiqui, Baozhou Sun

Faculty, Staff and Students Publications

Background: Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance.

Purpose: To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment.

Methods: TUM-SAM integrates nnU-Net-based lesion detection with a …

Hypovascular Aggressive Angiomyxoma In A Pregnant Adolescent: A Case Report And Review Of Its Multimodal Imaging Appearances, Kyler Shin, Kweku Agyepong, Craig Kym, Mohammad Ghasemi-Rad, David Léon

Faculty, Staff and Students Publications

Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that primarily arises in the perineum and pelvis of young females. It is sometimes identified incidentally on pelvic examination and obstetric imaging. Although asymptomatic at small sizes, AAM is typically hypervascular and can grow large enough to complicate a patient's obstetric and gynecologic course of treatment. While AAM is a rare diagnosis reported in the literature, there are limited descriptions of its multimodal radiologic appearance, and uncommonly, it can present as a hypovascular mass. We describe a rare case of hypovascular AAM in pregnancy that did not respond favorably to targeted embolization, …

Comprehensive Assessment Of Direct And Passive Smoking Across The Pancreatitis Spectrum, Samuel Han, Dhiraj Yadav, Jun Xu, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Liang Li, Stephen J Pandol, Walter G Park, Guru Trikudanathan, Stephen K Van Den Eeden, Santhi Swaroop Vege, Darwin L Conwell, Christie Y Jeon, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Smoking is a key risk factor for pancreatitis, contributing to pathogenesis and disease progression. Data regarding second-hand smoking, or passive smoking (PS) exposure, are lacking. We therefore aimed to assess the impact of PS exposure across the pancreatitis spectrum.

Methods: We analyzed baseline data from the PROCEED study, a multicenter study in the United States including patients with acute (AP), recurrent acute (RAP), and chronic (CP) pancreatitis. Participants detailed their individual smoking history and PS exposure, which was compared between AP, RAP, and CP subgroups. Participant factors and clinical characteristics were compared by level of individual and PS exposure. …

Homework Adherence In Exposure-Based Cbt For Youth With Obsessive-Compulsive Disorder: Clinical Outcomes And Predictors Across Treatment, Abigail E Pine, Qimin Liu, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Exposure-based cognitive behavioral therapy (CBT) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), but not all youth fully respond to this treatment. While multiple factors may influence CBT response, homework adherence in CBT is a modifiable target that can improve treatment outcomes. This report examines the relationship between homework adherence and clinical outcomes in a large sample of youth with OCD who received exposure-based CBT. Here, 137 youth with OCD between 7 and 17 years old (M = 12.42, SD = 2.88) participated in a randomized controlled trial of exposure-based CBT. Homework adherence was monitored weekly, and OCD severity …

Mental Health Stigma In Latin American Youth With Obsessive-Compulsive Disorder, Ryan J Mccarty, Matias Jensen, Elissa Paz Jensen Santa Cruz, Melisa N Sagarnaga, Pamela Claisse Quiroz, Tomás Miño, Paola Giusti-Rodriguez, Mayra C Martinez Mallen, Maria B Moyano, Dayan Berrones, Jacey L Anderberg, Renee M Frederick, Hannah C Moore, Josselyn S Muñoz, Vanessa Zavala Cruz, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Working Group (Gttoc), Ogechi C Onyeka, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is an impairing mental health condition that affects individuals across the lifespan. Some literature has evaluated mental health stigma in adults with OCD but limited attention has been given to youth, as well as those of Latino ancestry. The present study reported the extent of stigma experiences among Latin American youth with OCD, as well as examined sociodemographic, clinical and psychological correlates. 235 youth with clinician confirmed diagnoses of OCD from 10 North and South American countries completed questionnaires assessing stigma experiences, symptomatology, and functioning. Sociodemographic and clinical variables were also collected. The average OCD stigma response …

Caregiver Satisfaction With Anxiety Treatment For Autistic Youth: A Mixed Methods Examination, Lesley A Norris, Jonathan C Rabner, Marika Marklin, Margaret E Crane, Kathrin Renschler, Emma Jenkins, Joshua Kemp, Eric A Storch, Jeffrey J Wood, Connor M Kerns, Adam B Lewin, Brent J Small, Philip C Kendall

Faculty, Staff and Students Publications

For Cognitive Behavioral Therapy to best meet the specific needs of autistic youth with co-occurring anxiety and to continue to grow as a sustainable treatment option, it is important to incorporate caregiver perspectives and feedback. Data were drawn from a randomized controlled trial and included 148 caregivers of autistic youth (ages 7-13 years, M = 9.89, SD = 1.79; 23% female; 77.7% White) with co-occurring anxiety disorders randomized to one of two active treatment conditions (Coping Cat, n = 72, or Behavioral Interventions for Anxiety in Children with Autism [BIACA], n = 76). A systematic inductive thematic analysis was used …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Genetics Of Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have …

Jak Inhibition In Pnpt1-Related Mitochondrial Interferonopathy: A Case Report And Review Of Mitochondrial-Immune Crosstalk, Dan Ross Brooks, Hyun Yong Koh, Taylor Martin Kerrins, Steven Lang, Emily Bland, Rui Yang, Sarah Kogan Nicholas, Stephanie Jean Sikkink, Stephen Kralik, Christine Eng, Chaya Nautiyal Murali, Seema Lalani, Pilar Lenglet Magoulas, Lisa Emrick, Kristen Sydney Fisher, Fernando Scaglia

Faculty, Staff and Students Publications

Biallelic pathogenic variants in PNPT1 cause combined oxidative phosphorylation deficiency 13 (COXPD13) (MIM #614932), linking mitochondrial dysfunction to type I interferon (IFN) activation through cytosolic leakage of mitochondrial double‐stranded RNA (mt‐dsRNA). This mechanism connects mitochondrial disease to interferonopathies such as Aicardi–Goutières syndrome (AGS). We describe a 7‐month‐old female infant with compound heterozygous PNPT1 variants presenting with severe hypotonia, feeding difficulties necessitating gastrostomy, dystonia, and elevated serum lactate. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar, brainstem, and basal ganglia atrophy, with a lactate peak on MR spectroscopy (consistent with an inverted doublet). Serum immune profiling revealed a mild but elevated …

Statistics Of Natural Scenes Shape Contextual Modulation In The Visual Cortex, Jiakun Fu, Suhas Shrinivasan, Luca Baroni, Zhuokun Ding, Paul G Fahey, Paweł A Pierzchlewicz, Nikos Karantzas, Kayla Ponder, Rachel Froebe, Lydia Ntanavara, Taliah Muhammad, Konstantin F Willeke, Eric Wang, Zhiwei Ding, Dat Tran, Stelios Papadopoulos, Saumil Patel, Jacob Reimer, Alexander S Ecker, Xaq Pitkow, Jan Antolik, Fabian H Sinz, Ralf M Haefner, Andreas S Tolias, Katrin Franke

Faculty, Staff and Students Publications

Vision is context dependent, with neuronal responses shaped not only by local features but also by surrounding visual input. While classical studies, using grating stimuli, show that iso-oriented surrounds suppress responses more than orthogonal surrounds, the role of contextual modulation under natural stimulus conditions remains less clear. Using recordings from mouse primary visual cortex (V1), we trained convolutional neural network models to predict neuronal responses to natural images and synthesized surround stimuli that selectively suppressed or facilitated responses to optimal center inputs. In vivo experiments confirmed these predictions. Facilitatory surrounds resembled naturalistic continuations of the optimal center stimulus, consistent with …

Development Of An Educational Curriculum For The Surgical Implantation Of Dbs Systems, David Bieber, Rany T Abdallah, Alaa Ab-Elsayed, Adam R Burkey, Dario J Englot, Kunal Gupta, Charles N Munyon, Casey H Halpern, Kai J Miller, Joshua M Rosenow, Ahmed M Raslan, Konstantin V Slavin, Jennifer A Sweet, Sameer Sheth, Nestor Tomycz, Ashwin Viswanathan, Chengyuan Wu, Jeffrey S Raskin

Faculty, Staff and Students Publications

Background: Deep-brain stimulation (DBS) systems are implanted for movement disorders, epilepsy, and psychiatric conditions. Neurologic surgery remains the only discipline credentialed to implant DBS devices, although significant practice variation exists, partly due to heterogeneous training. The North American Neuromodulation Society (NANS) education committee offers a granular recommendation for the progression of an early learner through the practitioner level. It is contextualized within the six-core competency rubric for the surgical implantation of DBS devices.

Materials and methods: Guided by the Accreditation Council for Graduate Medical Education (ACGME) core competencies, a subcommittee of the NANS education committee met virtually and in-person over …

Fluocinolone Acetonide Implant As A Baseline Therapy For Diabetic Macular Edema: Results From The Randomized Phase 4 New Day Study, Michael A Singer, Charles C Wykoff, Christopher D Riemann, Victor H Gonzalez, Christina Y Weng, Kamel Alkhatib, Rohit A Amarshi, Scott Moody, Mary Pao

Faculty, Staff and Students Publications

Purpose: The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME).

Design: Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study.

Participants: Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST).

Methods: Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if …

Social Determinants As Pathways In Disparities In Oral Cavity Cancer Stage At Diagnosis: A Registry-Based Analysis From 2010–2020, Guillermo A Tortolero, Erich M Sturgis, Itunu O Sokale, Abiodun Oluyomi, Kristina R Dahlstrom, Aaron P Thrift

Faculty, Staff and Students Publications

Purpose: Racial and ethnic differences in oral cavity cancer (OCC) stage at diagnosis are substantial, but the reasons remain unclear. We assessed insurance status and social neighborhood factors as potential pathways.

Methods: Using the Texas Cancer Registry, we identified adults diagnosed with OCC between 2010 and 2020. We examined the crude and multivariable associations of race and ethnicity, insurance status, and social neighborhood factors with stage at diagnosis. We investigated the mediating effects of insurance status and neighborhood-level social factors on racial and ethnic differences in stage at diagnosis using four-way decomposition with modified Poisson regression and robust standard errors. …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Quality Domains In Home-Based Pediatric Hospice And Palliative Care: Adolescent And Young Adult Perspectives, Daniel H Grossoehme, Claire A Crawford, Jhansi Chandra Ellakula, Toluwalase Ajayi, Justin N Baker, Sarah Friebert, Lisa Humphrey, Jillann Jarrell, Rachel Thienprayoon, Pamela S Hinds

Faculty, Staff and Students Publications

Background: Current United States palliative care practice guidelines are intended to cover care across all age groups. Previous research with pediatric providers and caregivers concluded that pediatric hospice and palliative care have unique attributes. Not known is how adolescent hospice and palliative care patients understand quality palliative care. The purpose of this study was to characterize and define quality of care domains as described by adolescent and young adult patients receiving home-based hospice and palliative care.

Methods: Semi-structured interviews with 10-26 year-olds who received home-based hospice and/or palliative care visits in the prior three years at six diverse sites in …

Extended-Phase Anticoagulation For Pediatric Venous Thromboembolism After Einstein Jr, Nathan Wilken, Jun Teruya

Faculty, Staff and Students Publications

No abstract provided.

Fgfr3::Tacc3 Fusion And Notch1 Loss-Of-Function In A Case Of Hpv-Associated Sinonasal Squamous Cell Carcinoma: Diagnostic Challenge And Implications For Targeted Therapy, Xu Cao, Hong Yu, Reham Hamdy Abdulazim Soliman, Pei Ying, Songlin Zhang, Li Liang

Faculty, Staff and Students Publications

Sinonasal squamous cell carcinoma (SNSCC) comprises a heterogeneous group of tumors with emerging molecular subtypes. Human papillomavirus (HPV)-associated SNSCC is a distinct entity, although actionable genomic alterations beyond HPV-driven pathways remain underexplored. Distinguishing HPV-associated SNSCC from carcinoma ex inverted papilloma can be particularly challenging in limited biopsy specimens, as these lesions may appear morphologically similar. We report a case of HPV-associated SNSCC with concurrent FGFR3::TACC3 fusion and NOTCH1 p.C1416 stop-gain mutation.

Oncocytic Intraductal Carcinoma Of The Parotid Gland With Strn::Alk Fusion, Reham H Soliman, Chris Shi, Kevin E Fisher, Hong Yu, Fouad El-Dana, Xu Cao, Li Liang, Pei Ying, Songlin Zhang

Faculty, Staff and Students Publications

Intraductal carcinoma (IDC) of the salivary gland is an uncommon epithelial neoplasm characterized by a predominantly intraductal or intracystic proliferation rimmed by a myoepithelial cell layer. Advances in molecular profiling have revealed recurrent gene fusions in IDC, most frequently involving RET, although fusions implicating other kinase genes have also been described. Among these, ALK rearrangements are rare and remain poorly characterized. Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this …

Leading Healthcare Improvement: An Implementation Strategy, Kelley Arredondo, Anthony Ecker, Lindsay Vaclavik, Jacquelene Shahin, Ashley Thompson, Molly Horstman, David Ramsey, Kyler M Godwin

Faculty, Staff and Students Publications

Introduction: Healthcare professionals often implement quality improvement (QI) initiatives but lack training to implement and sustain QI initiatives. Leading Healthcare Improvement (LHI) is a course that combines principles from change management, team science, and leadership effectiveness into an implementation strategy to enable clinicians to lead sustainable change.

Methods: LHI is a 6-session, 4-month interactive training. Learners work on an active QI project throughout the course. A Wilcoxon signed-rank test was conducted to evaluate pre- and post-course changes in learners' self-reported confidence across five QI competencies.

Results: Veterans Healthcare Administration clinicians and fellows completed the LHI pre- (n = 111) and …

Effect Of Androgen Receptor Polymorphism On Hypogonadism Severity And Efficacy Of Testosterone Replacement Therapy, Nelson W Mills, Beatriz S Hernandez, Peyton J Coady, Arnaav Walia, Gal Saffati, Daniela Orozco Rendon, Dalia Khera, Nadia Khera, Weitao Song, Mohit Khera

Faculty, Staff and Students Publications

Background: The preferred treatment for hypogonadism, testosterone replacement therapy (TRT), has a varying efficacy that is currently not fully understood. This observation may be explained by polymorphism of the androgen receptor (AR), a ligand-binding transcription factor whose polyglutamine tract length affects various health conditions and androgen sensitivity. It has been theorized that this polymorphism may also affect the severity of hypogonadism. This study sought to determine a correlation between hypogonadism severity, TRT efficacy, and number of CAG trinucleotide repeats in the AR gene.

Methods: One hundred sixty-two males presenting to a single institution with symptoms of hypogonadism were recruited for …

Tusc3 Serves As A Rate-Limiting Gatekeeper Of A Glycan-Mediated Er Triage Checkpoint For Bmp4/Dpp, Antonio Galeone, Emilio Solazzo, Francesco Lavezzari, Seung Yeop Han, Gaia Consonni, Bruna My, Riccardo Rizzo, Giuseppe Gigli, Hamed Jafar-Nejad, Thomas Vaccari

Faculty, Staff and Students Publications

Trimming of the three glucose residues decorating nascent N-glycoproteins is a critical step for their entry into the endoplasmic reticulum quality control (ERQC) and recognition by ER chaperones. However, the functional relevance of the second glucose (G2) and the regulatory step upstream of its removal by glucosidase II (GCS2) remain poorly understood. Here, we report that TUSC3, a component of the oligosaccharyltransferase (OST) complex, regulates G2 to G1 trimming on N-glycosylated bone morphogenetic protein 4 (BMP4) and its Drosophila homolog Dpp to promote their ERQC entry. Loss- and gain-of-function genetic experiments and biochemical assays in mammalian cells and flies indicate …

Reply To: A Lethal Progressive Neuroinflammation Disguised As Mogad Revealing A Final Diagnosis Of Griscelli Syndrome: Regarding: Mogad Is The Most Common Cause Of Isolated Optic Neuritis In Children, Chaitanya Aduru, Akansha Chandrasekar, Kyla Blasingame, Jonathan Rosen, Jesse M Levine, Karla Salazar, Madhuri Chilakapati, Rod Foroozan, Victoria Adeseye, Jonathan M Yarimi, Nikita Shukla, Timothy E Lotze, Kristen S Fisher, Alexander J Sandweiss

Faculty, Staff and Students Publications

No abstract provided.

Chemotherapeutic Induction Of Cytosolic Single-Stranded Dna Accumulation Sensitizes Triple-Negative Breast Cancer To Immunotherapy, Yong Du, Li Yang, Hui Dai, Jianli Zhou, Zhicheng Zhou, Ruoxi Yuan, Rui Ye, Anh Thai Quynh Nguyen, Kishor Bhatia, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Background: Despite the widespread adoption of chemoimmunotherapy in triple-negative breast cancer (TNBC), the mechanisms by which cytotoxic chemotherapy engages antitumor immunity remain poorly defined. Identifying tumor-intrinsic immunogenic programs that predict and enhance responsiveness to immune checkpoint blockade (ICB) is therefore of critical clinical importance.

Methods: Transcriptomic signatures of TREX1 deficiency were generated from CRISPR-engineered TNBC models and applied to multiple independent TNBC cohorts treated with chemoimmunotherapy. Cytosolic single-stranded DNA (ssDNA) accumulation was quantified using a flow cytometry-based assay to functionally screen chemotherapeutic agents. Immune activation and therapeutic efficacy were evaluated using in vitro assays, syngeneic mouse tumor models, flow cytometry, …

Letter To The Editor: Hemodynamic Role In Hepatic Encephalopathy Pathogenesis Following Transjugular Intrahepatic Portosystemic Shunt Placement, John Halphen, Yash S Dayal, Cameron Laurie, Mohadese Ahmadzade, David Wynne, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Hepatic encephalopathy (HE) is a common complication following transjugular intrahepatic portosystemic shunt (TIPS) placement and is thought to result from reduced hepatic detoxification of neurotoxins. However, Zhuang et al in the World Journal of Radiology demonstrate that this understanding may be incomplete through exploration of the pathophysiology from a hemodynamic perspective. They found significant changes in cerebral blood flow (CBF) and spontaneous brain activity following TIPS. Initially, CBF increased in specific areas within the first month, followed by a return to baseline at three months. These CBF changes coincided with increased spontaneous brain activity that persisted in some areas, suggesting …

Long-Term Functional Synaptic Integration Of Genome-Edited Retinal Organoids In A Primate Model Of Macular Degeneration, Atsuta Ozaki, Akihiro Kawai, Ryutaro Akiba, Satoko Okayama, Nobuhiko Ohno, Keisuke Kajita, Tomohiro Masuda, Satoshi Yokota, Shin-Ichiro Ito, Du Peiyan, Kenta Onoue, Shigenobu Yonemura, Mineo Kondo, Yasuo Kurimoto, Yingbin Fu, Michiko Mandai

Faculty, Staff and Students Publications

Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1-/- human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation non-human primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography, we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses …