Digital Commons Network^™

Unveiling Vaginal Fibrosis: A Novel Murine Model Using Bleomycin And Epithelial Disruption, Jennifer M Mccracken, Gisele A Calderon, Felipe Rivas, Dorothea Erxleben, Taylor Moseley, Lishore A Kumar, Daniel E Kennedy, Swathi Balaji, Adam Hall, Julie C E Hakim

Faculty, Staff and Students Publications

Vaginal fibrosis induced by cancer therapy continues to take a physical and psychoemotional burden. To advance the efforts to generate a reproducible and cost-effective animal model, we tested the effect of repeated bleomycin instillations with mucosal layer disruption on induction of vaginal fibrosis. Tissue samples collected at various time points were analyzed for fibrosis-related gene expression changes and collagen content. Low (1.5 U/kg) and high-dose (2.5 U/kg) bleomycin instillations alone did not induce fibrosis, but when high-dose bleomycin was combined with epithelial disruption, increased profibrotic gene expression and trichrome staining were observed. To evaluate spatial and temporal changes in the …

Exploration Of Cytokines And Microbiome Among Males And Females With Diarrhea-Predominant Irritable Bowel Syndrome, Li Juen Chen, Anna M Plantinga, Robert Burr, Kevin Cain, Pamela Barney, Tor Savidge, Robert J Shulman, Margaret Heitkemper, Kendra Kamp

Faculty, Staff and Students Publications

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine …

Insulin-Like Growth Factor Binding Protein-3 (Igfbp-3): A Biomarker Of Coronary Artery Disease Induced Myocardial Ischaemia, Jacqui A Lee, Jessika Wise, Sara D Raudsepp, Louise N Paton, Jan Powell, Kieran Jina, Sally Aldous, Richard W Troughton, Philip D Adamson, A Mark Richards, W Frank Peacock, James L Januzzi, Noah Erceg, Luca Koechlin, Jasper Boeddinghaus, Pedro Lopez-Ayala, Christian Mueller, Martin P Than, John W Pickering, Chris J Pemberton

Faculty, Staff and Students Publications

Aims: Among individuals presenting to the emergency department (ED) with chest pain, clinical uncertainty surrounds the appropriate identification of non-myocardial infarction (MI) individuals who would most benefit from objective functional/anatomical testing (e.g. imaging). We applied a proteomic biomarker discovery approach to identify novel candidates reflecting coronary artery disease (CAD) induced ischaemia that could translate to measurement in clinical samples.

Methods and results: Mass spectroscopy (MS) of perfusate from an isolated rat heart model of cardiac ischaemia identified >100 novel protein biomarkers. A prominent candidate, insulin-like growth factor binding protein (IGFBP-3), was then interrogated for its ability to identify CAD-related ischaemia …

Neuro-Ophthalmic Complications Following Eighth Cranial Nerve Microvascularx Decompression, Stanley M Saju, Patrick J Hunt, Pamela Davila-Siliezar, Noor Laylani, Andrew G Lee

Faculty, Staff and Students Publications

Purpose: To discuss a novel diagnosis of post-surgical iatrogenic AICA vasospasm following eighth cranial nerve microvascular decompression as the most likely etiology for a lateral pontine infarct.

Observations: A 49-year-old male presented with tinnitus, vertigo, binocular and monocular diplopia following left occipital decompressive craniectomy and microvascular decompression of cranial nerve VIII. Magnetic resonance imaging demonstrated patent vasculature with evolution of a subacute infarct of the left lateral pons and middle cerebellar peduncle in the territory of the left AICA.

Conclusions: We report a unique case of lateral pontine infarction without vascular occlusion acutely following surgical microvascular decompression of CN VIII, …

Learning Soft Tissue Deformation From Incremental Simulations, Nathan Lampen, Daeseung Kim, Xuanang Xu, Xi Fang, Jungwook Lee, Tianshu Kuang, Hannah H Deng, Michael A K Liebschner, Jaime Gateno, Pingkun Yan

Faculty, Staff and Students Publications

Background: Surgical planning for orthognathic procedures demands swift and accurate biomechanical modeling of facial soft tissues. Efficient simulations are vital in the clinical pipeline, as surgeons may iterate through multiple plans. Biomechanical simulations typically use the finite element method (FEM). Prior works divide FEM simulations into increments to enhance convergence and accuracy. However, this practice elongates simulation time, thereby impeding clinical integration. To accelerate simulations, deep learning (DL) models have been explored. Yet, previous efforts either perform simulations in a single step or neglect the temporal aspects in incremental simulations.

Purpose: This study investigates the use of spatiotemporal incremental modeling …

Anesthetic Considerations For Repair Of Thoracoabdominal Aortic Aneurysms, David A Lyubashevsky, Thomas Powell, Ali Khalifa, Vicente Orozco-Sevilla, Daniel A Tolpin

Faculty, Staff and Students Publications

Anesthetic management of open thoracoabdominal aneurysm (TAAA) repair poses a number of challenges for even the most experienced of cardiovascular anesthesiologists. This procedure encompasses a large number of unique anesthetic techniques, including one-lung ventilation, invasive hemodynamic monitoring, left-heart bypass, massive transfusion, selective renal and visceral perfusion, and central nervous system monitoring with CSF drainage. In this article, we aim to describe the anesthetic management for thoracoabdominal aortic aneurysm repair, including preoperative workup, intraoperative management, as well as postoperative concerns in the intensive care unit.

A Multicenter Training And Interrater Reliability Study Of The Based Score For Infantile Epileptic Spasms Syndrome, John R Mytinger, Dara V F Albert, Shawn C Aylward, Christopher W Beatty, Sonam Bhalla, Sonal Bhatia, Guy N Brock, Micheal A Ciliberto, Purva R Choudhari, Daniel J Clark, Jennifer Madan Cohen, Theresa M Czech, Megan M Fredwall, Ernesto Gonzalez-Giraldo, Chellamani Harini, Senyene E Hunter, Amanda G Sandoval Karamian, Akshat Katyayan, Isaac Kistler, Neil Kulkarni, Virginia B Liu, Corinne Mccabe, Thomas Murray, Kerri Neville, Shital H Patel, Spriha Pavuluri, Donald J Phillips, Debopam Samanta, Deepa Sirsi, Emily M Spelbrink, Carl E Stafstrom, Maija Steenari, Danielle S Takacs, Tyler Terrill, Linh Tran, Jorge Vidaurre, Daniel W Shrey

Faculty, Staff and Students Publications

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE).

METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 …

A Predictive Chromatin Architecture Nexus Regulates Transcription And Dna Damage Repair, Audesh Bhat, Sonali Bhan, Aindrila Kabiraj, Raj K Pandita, Keneth S Ramos, Sandhik Nandi, Shreya Sopori, Parthas S Sarkar, Arti Dhar, Shruti Pandita, Rakesh Kumar, Chandrima Das, John A Tainer, Tej K Pandita

Faculty, Staff and Student Publications

Genomes are blueprints of life essential for an organism's survival, propagation, and evolutionary adaptation. Eukaryotic genomes comprise of DNA, core histones, and several other nonhistone proteins, packaged into chromatin in the tiny confines of nucleus. Chromatin structural organization restricts transcription factors to access DNA, permitting binding only after specific chromatin remodeling events. The fundamental processes in living cells, including transcription, replication, repair, and recombination, are thus regulated by chromatin structure through ATP-dependent remodeling, histone variant incorporation, and various covalent histone modifications including phosphorylation, acetylation, and ubiquitination. These modifications, particularly involving histone variant H2AX, furthermore play crucial roles in DNA damage …

Robust Automated Method Of Spatial Resolution Measurement In Radiotherapy Ct Simulation Images, Pavel Govyadinov, Rick R Layman, Tucker Netherton, Raymond Mumme, Aaron K Jones, Laurence E Court, Moiz Ahmad

Faculty, Staff and Student Publications

Background: Variation in imaging protocol, patient positioning, and the presence of artifacts can vary image quality in CT images used for radiotherapy planning. Automated methods for spatial resolution (SR) estimation exist but require further investigation and validation for wider adoption.

Purpose: To validated previously existing algorithm for SR estimation and introduce improvements that make it robust to patient positioning, CT protocol, site, and artifacts.

Method: A reference algorithm based on the previous gold standard was recreated and modified to improve robustness. The algorithms were tested on three different datasets: (1) a cylindrical ACR CT QC phantom scanned using a Siemens …

Clinical Use Of Gafchromic Ebt4 Film For In Vivo Dosimetry For Total Body Irradiation, Emily Draeger, Fada Guan, Min-Young Lee, Dae Yup Han, William Donahue, Zhe Jay Chen

Faculty, Staff and Student Publications

Purpose: In vivo dosimetry is a common requirement to validate dose accuracy/uniformity in total body irradiation (TBI). Several detectors can be used for in vivo dosimetry, including thermoluminescent dosimeters (TLDs), diodes, ion chambers, optically stimulated luminescent dosimeters (OSLDs), and film. TLDs are well established for use in vivo but required expertise and clinical system availability may make them impractical for multifractionated TBI. OSLDs offer quick readout, but recalls have restricted their use. The purpose of this work was to validate the newly available Gafchromic EBT4 film for TBI in vivo dosimetry.

Methods: Film calibration curves were created under standard conditions …

Seq-Scope: Repurposing Illumina Sequencing Flow Cells For High-Resolution Spatial Transcriptomics, Yongsung Kim, Weiqiu Cheng, Chun-Seok Cho, Yongha Hwang, Yichen Si, Anna Park, Mitchell Schrank, Jer-En Hsu, Angelo Anacleto, Jingyue Xi, Myungjin Kim, Ellen Pedersen, Olivia I Koues, Thomas Wilson, Changhee Lee, Goo Jun, Hyun Min Kang, Jun Hee Lee

Faculty, Staff and Student Publications

Spatial transcriptomics technologies aim to advance gene expression studies by profiling the entire transcriptome with intact spatial information from a single histological slide. However, the application of spatial transcriptomics is limited by low resolution, limited transcript coverage, complex procedures, poor scalability and high costs of initial setup and/or individual experiments. Seq-Scope repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, overcoming these limitations. It offers submicrometer resolution, high capture efficiency, rapid turnaround time and precise annotation of histopathology at a much lower cost than commercial alternatives. This protocol details the implementation of Seq-Scope with an Illumina NovaSeq 6000 …

Medical Image Segmentation Assisted With Clinical Inputs Via Language Encoder In A Deep Learning Framework, Hengrui Zhao, Biling Wang, Deepkumar Mistry, Jing Wang, Michael Dohopolski, Daniel Yang, Weiguo Lu, Steve Jiang, Dan Nguyen

Faculty, Staff and Student Publications

Introduction: Auto-segmentation of tumor volumes and organs at risk (OARs) is a critical step in cancer radiotherapy treatment planning, where rapid, precise adjustments to treatment plans are required to match the patient anatomy. Although auto-segmentation has been clinically accepted for most OARs, auto-segmentation of tumor volumes, particularly clinical target volumes (CTVs), remains a challenge. This difficulty arises because images alone are often insufficient to capture the necessary information for accurate delineation of microscopic tumor invasion invisible on the image itself.

Methods: We propose a deep learning-based medical image segmentation framework designed to mimic the clinical process of delineating CTVs and …

Difference-Makers For Collecting Sexual Orientation And Gender Identity Data In Oncology Settings, Mandi L Pratt-Chapman, Edward J Miech, Megan A Mullins, Shine Chang, Gwendolyn P Quinn, Shail Maingi, Matthew B Schabath, Charles Kamen

Faculty, Staff and Student Publications

Purpose: The purpose of this analysis was to identify key difference-making conditions that distinguish oncology institutions that collect sexual orientation and gender identity (SOGI) data across a sample of American Society of Clinical Oncology (ASCO) members.

Methods: From October to November 2020, an anonymous 54-item web-based survey was distributed to ASCO members. Coincidence analysis was used to identify difference-making conditions for the collection of SOGI data.

Results: ASCO members' responses to just three items consistently distinguished practices that reported collecting both SO and GI data (n = 25) from those who did not (n = 20): (1)."Do you ask your …

An Automated Treatment Planning Portfolio For Whole Breast Radiotherapy, Hana Baroudi, Leonard Che Fru, Deborah Schofield, Dominique L Roniger, Callistus Nguyen, Donald Hancock, Christine Chung, Beth M Beadle, Kent A Gifford, Tucker Netherton, Joshua S Niedzielski, Adam Melancon, Manickam Muruganandham, Meena Khan, Simona F Shaitelman, Sanjay Shete, Patricia Murina, Daniel Venencia, Sheeba Thengumpallil, Conny Vrieling, Joy Zhang, Melissa P Mitchell, Laurence E Court

Faculty, Staff and Student Publications

Background: Automation in radiotherapy presents a promising solution to the increasing cancer burden and workforce shortages. However, existing automated methods for breast radiotherapy lack a comprehensive, end-to-end solution that meets varying standards of care.

Purpose: This study aims to develop a complete portfolio of automated radiotherapy treatment planning for intact breasts, tailored to individual patient factors, clinical approaches, and available resources.

Methods: We developed five automated conventional treatment approaches and utilized an established RapidPlan model for volumetric arc therapy. These approaches include conventional tangents for whole breast treatment, two variants for supraclavicular nodes (SCLV) treatment with/without axillary nodes, and two …

A Combination Of Low Doses Of Lithium And Valproate Improves Cognitive Outcomes After Mild Traumatic Brain Injury, John B Redell, Mark E Maynard, Michael J Hylin, Kimberly N Hood, Andrea Sedlock, Dragan Maric, Jing Zhao, Anthony N Moore, Badrinath Roysam, Shibani Pati, Pramod K Dash

Faculty, Staff and Student Publications

The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + …

Erratum: Comparison Of The Neer Classification To The 2018 Update Of The Orthopedic Trauma Association/Ao Fracture Classification For Classifying Proximal Humerus Fractures: Erratum, Meir T Marmor, Julie Agel, Jarrod Dumpe, James F Kellam, Geoffrey S Marecek, Eric Meinberg, Mai P Nguyen, Stephen Sims, Gillian L Soles, Matthew D Karam

Faculty, Staff and Student Publications

This corrects the article "Comparison of the Neer classification to the 2018 update of the Orthopedic Trauma Association/AO fracture classification for classifying proximal humerus fractures" in volume 5, e200.

Synchronous Presentation Of Right Parotid Branchial Cleft Cyst And Left Neck Hpv-Associated Cystic Metastatic Squamous Cell Carcinoma: A Diagnostic Quandary, Syed H A Naqvi, Syed H S Naqvi, David Allen, Arturo A Eguia, Jing Liu, Ron J Karni

Faculty, Staff and Student Publications

Branchial cleft cyst arising within the parotid space is considered an extremely rare phenomenon. In contrast, cystic squamous cell carcinoma in the lateral neck is not an uncommon presentation of HPV-related head and neck cancer. Although they have singly been narrated in literature, simultaneous expression of these anomalies has yet to be reported. We describe a case of synchronous presentation of branchial cleft cyst of the right parotid gland and cystic metastatic squamous cell carcinoma of the left neck. These findings are discussed in light of the challenges in fine needle aspiration biopsy of cystic masses, and the risk of …

Bilateral Macronodular Adrenocortical Disease: A Single Centre Experience, Anuj Ban, Rohit Barnabas, Manjiri Karlekar, Anurag Ranjan Lila, Chethan Yami Channaiah, Saba Samad Memon, Virendra A Patil, Vijaya Sarathi, Gwendolyn Fernandes, Hemangini Thakkar, Sameer Rege, Nalini S Shah, Tushar Bandgar

Faculty, Staff and Student Publications

Background: Data on bilateral macronodular adrenocortical disease (BMAD) with respect to computed tomography (CT) scan characteristics (attenuation and washout) and long-term follow-up are limited. This study aims to describe BMAD patients managed in a single centre.

Methods: BMAD was defined by the presence of bilateral adrenal macronodules (>1 cm) on CT. Clinical, biochemical, radiological, genetic characteristics, management and follow-up of 22 BMAD patients were studied retrospectively.

Results: The median age (range) at presentation was 49.5 (23-83) years, predominantly observed in females (16/22). Eighteen (82%) patients were incidentally diagnosed (11 with mild autonomous cortisol secretion (MACS) and seven non-secretory), three …

The Associations Of Sensory Impairment With 10-Year Risk Of Dementia And Alzheimer's Disease: The Health And Retirement Study, 2010-2020, Kun Li, Rahul Ghosal, Donglan Zhang, Yike Li, Matthew C Lohman, Monique J Brown, Anwar T Merchant, Chih-Hsiang Yang, Jean Neils-Strunjas, Daniela B Friedman, Jingkai Wei

Faculty, Staff and Student Publications

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. …

Endovascular Therapy In Patients With Acute Ischemic Stroke With Large Infarct: A Guideline From The Society Of Vascular And Interventional Neurology, Maxim Mokin, Tudor G Jovin, Sunil A Sheth, Thanh N Nguyen, Kaiz S Asif, Ameer E Hassan, Ashutosh P Jadhav, Cynthia Kenmuir, David S Liebeskind, Ossama Mansour, Raul G Nogueira, Robin Novakovic, Santiago Ortega-Gutierrez, Albert J Yoo, Waldo R Guerrero, Amer M Malik

Faculty, Staff and Student Publications

Background: Recent randomized clinical trials of endovascular therapy in patients with large infarct provided new evidence in support of endovascular interventions in patients with acute ischemic stroke. The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee aims to provide up-to-date recommendations on focused relevant clinical questions. Here, we review current evidence and provide recommendations for the selection and endovascular treatment of patients with anterior circulation large vessel occlusion and large infarct.

Methods: The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the …

Curq+ With Resveratrol Diminish Joint Pain In A Child With Pseudoachondroplasia: A Case Report, Jacqueline T Hecht, Ana-Coral Barreda-Bonis, Karen L Posey

Faculty, Staff and Student Publications

This case report details the successful use of over-the-counter resveratrol and CurQ+ in a five-year-old with pseudoachondroplasia (PSACH), a severe dwarfing condition caused by mutations in cartilage oligomeric matrix protein (COMP). Disproportionate short stature, abnormal joints, joint deformities, and pain starting in early childhood are characteristic findings. Adult treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and joint replacement to manage joint pain. Childhood pain goes largely untreated given the concern of daily use of NSAIDs in the very young. Recently, resveratrol has been shown to reduce pain and CurQ+ improves growth in a mouse model of PSACH. The use of these …

Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography, Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Significance: Systemic sclerosis (SSc) is a chronic idiopathic disease that causes immune dysregulation, vasculopathy, and organ fibrosis that affects more than 3 million people in the US alone. The modified Rodnan skin score (mRSS) is the current gold standard for diagnosing and staging skin fibrosis in SSc. However, mRSS is subjective, requires extensive training, and has high observer variability.

Aim: We aim to provide a quantitative method for the assessment of fibrosis.

Approach: We utilized optical coherence tomography (OCT), its extensions, optical coherence elastography (OCE), and OCT angiography (OCTA) to evaluate SSc-like fibrosis and therapy response in a mouse model. …

[Treatment Adherence For Attention Deficit Hyperactivity Disorder (Adhd) In The Champ Ut-Health Houston Program], Rachitha P Jadala, Hali Temkin, Kerri L Daniel, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: ADHD has a safe and effective treatment, but treatment adherence is often low. Several factors contribute to this low adherence, some of which are modifiable.

Methods: We conducted a literature review of recent studies on medication adherence in children and adolescents with ADHD. We gathered data on ADHD treatment adherence from our clinic in the ADHD Program and the Child and Adolescent Mood Disorders Program (ChAMP) at the University of Texas Health-Houston Program. We analyzed factors related to medication adherence, such as patient age, sex, prescription type, release formula, and their association with adherence in 117 patients with ADHD …

Genomic Characterisation Of The Relationship And Causal Links Between Vascular Calcification, Alzheimer’S Disease, And Cognitive Traits, Emmanuel O. Adewuyi, Simon M. Laws

Research outputs 2022 to 2026

Background/Objectives: Observational studies suggest a link between vascular calcification and dementia or cognitive decline, but the evidence is conflicting, and the underlying mechanisms are unclear. Here, we investigate the shared genetic and causal relationships of vascular calcification—coronary artery calcification (CAC) and abdominal aortic calcification (AAC)—with Alzheimer’s disease (AD), and five cognitive traits. Methods: We analyse large-scale genome-wide association studies (GWAS) summary statistics, using well-regarded methods, including linkage disequilibrium score regression (LDSC), Mendelian randomisation (MR), pairwise GWAS (GWAS-PW), and gene-based association analysis. Results: Our findings reveal a nominally significant positive genome-wide genetic correlation between CAC and AD, which becomes non-significant after …

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …

Comparison Of Deep Learning And Traditional Machine Learning Models For Predicting Mild Cognitive Impairment Using Plasma Proteomic Biomarkers, Kesheng Wang, Donald A. Adjeroh, Wei Fang, Suzy M. Walter, Danqing Xiao, Ubolrat Piamjariyakul, Chun Xu

Health & Biomedical Sciences Faculty Publications

Mild cognitive impairment (MCI) is a clinical condition characterized by a decline in cognitive ability and progression of cognitive impairment. It is often considered a transitional stage between normal aging and Alzheimer’s disease (AD). This study aimed to compare deep learning (DL) and traditional machine learning (ML) methods in predicting MCI using plasma proteomic biomarkers. A total of 239 adults were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort along with a pool of 146 plasma proteomic biomarkers. We evaluated seven traditional ML models (support vector machines (SVMs), logistic regression (LR), naïve Bayes (NB), random forest (RF), k-nearest neighbor …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Wmh Contributions To Cognitive Impairment: Rationale And Design Of The Diverse Vcid Study, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason Hinman, David K Johnson, Danielle Harvey, Myriam Fornage

Faculty, Staff and Student Publications

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter …

Guidelines For Minimal Reporting Requirements, Design And Interpretation Of Experiments Involving The Use Of Eukaryotic Dual Gene Expression Reporters (Mindr), Gary Loughran, Dmitry E Andreev, Ilya M Terenin, Olivier Namy, Martin Mikl, Martina M Yordanova, C Joel Mcmanus, Andrew E Firth, John F Atkins, Christopher S Fraser, Zoya Ignatova, Shintaro Iwasaki, Joanna Kufel, Ola Larsson, Sebastian A Leidel, Alexander S Mankin, Marco Mariotti, Marvin E Tanenbaum, Ivan Topisirovic, Nora Vázquez-Laslop, Gabriela Viero, Neva Caliskan, Yiwen Chen, Patricia L Clark, Jonathan D Dinman, Philip J Farabaugh, Wendy V Gilbert, Pavel Ivanov, Jeffrey S Kieft, Oliver Mühlemann, Matthew S Sachs, Ivan N Shatsky, Nahum Sonenberg, Anna-Lena Steckelberg, Anne E Willis, Michael T Woodside, Leos Shivaya Valasek, Sergey E Dmitriev, Pavel V Baranov

Faculty, Staff and Student Publications

Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. …

Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen

Faculty, Staff and Student Publications

Background: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.

Objective: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with …