Medicine and Health Sciences Commons^™

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Mechanisms Of Change Of A Multifaceted Implementation Strategy On Fidelity To A Guideline For The Prevention Of Mental Health Problems At The Workplace: A Mechanism Analysis Within A Cluster-Randomized Controlled Trial, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak

2020-Current year OA Pubs

BACKGROUND: Occupational guidelines exist to support workplaces with the prevention of mental health problems (MHP) among their staff. However, knowledge of effective implementation strategies to support their implementation is limited. This study experimentally tested whether a multifaceted implementation strategy - comprising an educational meeting, five workshops, implementation teams, small cyclical tests of change, and facilitation - improves fidelity to a guideline for preventing MHP in a school setting through the pathway of change of the Capability Opportunity Motivation-Behavior (COM-B)-model. To gain a more granular understanding of the mechanisms of change, the Theoretical Domains Framework (TDF) was used to specify mediators …

Development Of An Age-Appropriate Household Dysfunction Measure And Its Concurrent Validity With Multiple Outcomes Among Middle School Adolescents In Southeast Texas, Sumaita Choudhury, Timothy J Walker, Emily T Hébert, Christine M Markham, Ross Shegog, Robert C Addy, Melissa F Peskin

Faculty, Staff and Student Publications

Existing adverse childhood experience (ACE) measures include a limited number of household dysfunction (HD) items and the use of adult-oriented language that is not always appropriate for middle schoolers. We developed an age-appropriate 10-item HD measure informed by previously validated ACE measures and tested its concurrent validity with dating violence (DV) perpetration, lifetime substance use, and mental health outcomes among middle schoolers in Southeast Texas. This cross-sectional study used the baseline data from a DV prevention intervention program for sixth graders (N = 126), Me & You Tech. Baseline data were collected from March 2023 to April 2023. To …

Preterm Birth Increases Susceptibility To Hyperglycemia Induced Glomerular Alterations In Male Mice, Aleksandra Cwiek, Kevin M Bennett, Edwin J Baldelomar, Et Al.

2020-Current year OA Pubs

Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project was to determine the effect of preterm birth on kidney health after exposure to hyperglycemia. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, …

Methylation Risk Score Of C-Reactive Protein Associates Sleep Health With Related Health Outcomes, Ziqing Wang, Danielle A Wallace, Brian W Spitzer, Tianyi Huang, Kent D Taylor, Jerome I Rotter, Stephen S Rich, Peter Y Liu, Martha L Daviglus, Lifang Hou, Alberto R Ramos, Sonya Kaur, J Peter Durda, Hector M González, Myriam Fornage, Susan Redline, Carmen R Isasi, Tamar Sofer

Faculty, Staff and Student Publications

C-reactive protein (CRP) reflects inflammation status and is linked to poor sleep, metabolic and cardiovascular health. Methylation (MRS) and polygenic risk scores (PRS) reflect long-term systemic inflammation, and genetically-determined CRP, respectively. To refine understanding of inflammation-linked sleep and health outcomes, we construct PRS-CRPs using GWAS summary statistics and a previously-developed MRS-CRP in the Hispanic Community Health Study/Study of Latinos. Via survey-weighted linear regression, we estimate associations between blood-, PRS-, and MRS-CRP, with multiple sleep and health outcomes (n = 2217). MRS-CRP and PRS-CRPs are associated with increasing blood-CRP level by 43% and 23% per standard deviation. MRS-CRP is associated with …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

The Impact Of Breast Radiotherapy On The Tumor Genome And Immune Ecosystem, Aislyn Schalck, Tuan Tran, Jianzhuo Li, Emi Sei, Shanshan Bai, Min Hu, Jerome Lin, Scott J Bright, Samuel Reddick, Fei Yang, Harsh Batra, Alejandro Contreras, Maria Gabriela Raso, Michael C Stauder, Karen E Hoffman, Jay P Reddy, Kevin T Nead, Benjamin D Smith, Gabriel O Sawakuchi, Wendy A Woodward, Stephanie S Watowich, Jennifer K Litton, Isabelle Bedrosian, Elizabeth A Mittendorf, Huong Le-Petross, Nicholas E Navin, Simona F Shaitelman

Faculty, Staff and Student Publications

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. …

Methods For Joint Modeling Of Longitudinal Omics Data And Time-To-Event Outcomes: Applications To Lysophosphatidylcholines In Connection To Aging And Mortality In The Long Life Family Study, Konstantin G Arbeev, Olivia Bagley, Svetlana V Ukraintseva, Alexander Kulminski, Eric Stallard, Michaela Schwaiger-Haber, Gary J Patti, Yian Gu, Anatoliy I Yashin, Michael A Province

2020-Current year OA Pubs

Studying the relationships between longitudinal changes in omics variables and event risks requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process models [SPM]) to longitudinal metabolomics data from the Long Life Family Study, focusing on the understudied associations of longitudinal changes in lysophosphatidylcholines (LPCs) with mortality and aging-related outcomes. We analyzed 23 LPC species, with 5,066 measurements of each in 3,462 participants, 1,245 of whom died during follow-up. JM analyses found that higher levels of the majority of LPC species were associated with lower mortality risks, with the …

The Impact Of Narratives And Active Video Games Among Black And Hispanic Children With Overweight And Obesity: A Randomized Controlled Trial, Amy S Lu, Tom Baranowski, Tiago V Barreira, Amy Fleischman, Melanie C Green, Shirley Y Huang, I-Min Lee, Lynne L Levitsky, Farzad Noubary, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Overweight and obesity disproportionately affect Black and Hispanic children who also play more video games. Narratives, coupled with home-based active video games (AVGs), may enhance PA and mitigate these disparities. This study tested the effect of narrative-enhanced home-based AVGs among predominantly Black and Hispanic children with overweight and obesity.

Methods: This 6-month three-group RCT recruited 135 children aged 7-14 from pediatric clinics in Boston, MA (January 2020 - May 2022) during the COVID-19 pandemic. Participants were randomized into: [Narrative + AVG], receiving an Xbox/Kinect with six AVGs interspersed with a narrative animation Ataraxia (72 episodes over six months), which …

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

A Review Of Medical Ethics In Orthopaedic Surgery: Current Foci And Future Considerations, Ryan X Lam, Zhi Mei Sonia He, Ruhi Thapar, Maggie Wang, Dion G Birhiray, Matthew Milad, Lara Ouellette, Umar Ghilzai, Tucker J Cushing, M Brent Price, Brenden B Ronna, Omar H Atassi, Christopher H Perkins, John R Dawson, William M Granberry, Melvyn A Harrington, Douglas R Dirschl, Lorenzo R Deveza

Library Staff Publications

Medical ethics education is a required component of orthopaedic surgery resident training per the Accreditation Council for Graduate Medical Education (ACGME) guidelines, although no standardized curriculum currently exists.

Beyond the 4 principles of bioethics (autonomy, beneficence, nonmaleficence, justice), additional ethical concepts relevant to orthopaedic care include utilitarianism, deontology, virtue ethics, moral intuitionism, microethics, and narrative ethics.

Ethical themes identified in the literature relevant to orthopaedic surgery include the ethics involved in medical decision-making, use of new technologies, caring for vulnerable patients, performing high-stakes procedures, the impacts of trainee status on patient care, and patient attitude regarding conflict of interest.

Ethical …

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Decoding Resistance To Immune Checkpoint Inhibitors In Non-Small Cell Lung Cancer: A Comprehensive Analysis Of Plasma Proteomics And Therapeutic Implications, Michal Harel, Nili Dahan, Coren Lahav, Eyal Jacob, Yehonatan Elon, Igor Puzanov, Ronan J. Kelly, Yuval Shaked, Raya Leibowitz, David P. Carbone, David R. Gandara, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic analysis of plasma proteomic profiles to explore the underlying biology of treatment resistance in NSCLC.

METHODS: The analysis was performed on 388 "resistance-associated proteins" (RAPs) that were previously described as pretreatment plasma proteomic predictors within the PROphet computational model designed to predict ICI clinical benefit in NSCLC. Putative tissue origins of the RAPs were explored using publicly available datasets. Enrichment analyses were performed to investigate RAP-related biological …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

A Cross-Sectional Study Of The Role Of Epithelial Cell Injury In Kidney Transplant Outcomes, Philip F. Halloran, Tarek Alhamad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

METHODS: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

RESULTS: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. …

Subcortical Correlates Of Consciousness With Human Single Neuron Recordings, Michael Pereira, Nathan Faivre, Fosco Bernasconi, Nicholas Brandmeir, Jacob E Suffridge, Kaylee Tran, Shuo Wang, Victor Finomore, Peter Konrad, Ali Rezai, Olaf Blanke

2020-Current year OA Pubs

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness remains unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing …

In Vivo Crispr Activation Screen Identifies Acyl-Coa-Binding Protein As A Driver Of Bone Metastasis, Hongqi Teng, Qinglei Hang, Caishang Zheng, Yuelong Yan, Shaomin Liu, Yang Zhao, Yalan Deng, Litong Nie, Weiche Wu, Marisela Sheldon, Zachary Yu, Wei Shi, Jianxuan Gao, Chenling Meng, Consuelo Martinez, Jie Zhang, Fan Yao, Yutong Sun, Di Zhao, Boyi Gan, Tong Meng, Li Ma

Faculty, Staff and Student Publications

One of the most common sites of cancer metastasis is to the bone. Bone metastasis is associated with substantial morbidity and mortality, and current therapeutic interventions remain largely palliative. Metastasizing tumor cells need to reprogram their metabolic states to adapt to the nutrient environment of distant organs; however, the role and translational relevance of lipid metabolism in bone metastasis remain unclear. Here, we used an in vivo CRISPR activation screening system coupled with positive selection to identify acyl-coenzyme A (CoA) binding protein (ACBP) as a bone metastasis driver. In nonmetastatic and weakly metastatic cancer cells, overexpression of wild-type ACBP, but …

A Review Of Mirvetuximab Soravtansine-Gynx In Folate Receptor Alpha-Expressing Platinum-Resistant Ovarian Cancer, Judith A Smith, Patrick Medina, Mary Miao, Kathleen N Moore

Faculty, Staff and Student Publications

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces …

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

Treatment Of Overactive Katp Channels With Glibenclamide In A Zebrafish Model And A Clinical Trial In Humans With Cantú Syndrome, Lotte Kleinendorst, Sarah E Siegelaar, Helen I Roessler, Lema Meiwand, Malou Van Den Boogaard, Rianne H A C M De Bruin-Bon, Kirsten F Van Duinen, R Nils Planken, Elisabeth H Jaspars, Patrick M J H Kemperman, Berto J Bouma, Colin G Nichols, Marcel W Bekkenk, Gijs W Van Haaften, Mieke M Van Haelst

2020-Current year OA Pubs

This study explores the efficacy of glibenclamide, a K

Identification Of Surrogate Biomarkers For Mucopolysaccharidosis Type Iva, Yasuhiko Ago, Shaukat Khan, Kimberly Klipner, Allison Bradford, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 …

Evaluation Of Knowledge, Attitudes And Vaccine Hesitancy Towards Mmr Vaccine Among Parents In The United Arab Emirates, Kamel A. Samara, Hiba Jawdat Barqawi, Deema M. Alhayali, Samah Mohamed Kannas, Rim M. Elmorsy, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: The Measles, Mumps, and Rubella (MMR) vaccine is highly effective, but vaccine hesitancy (VH) is a key barrier to achieving herd immunity. This study aims to assess the general attitudes and knowledge of UAE parents regarding measles and the MMR vaccine while identifying determinants of VH.

METHODOLOGY: A cross-sectional study was done from 15th April 2024 and 5th June 2024. This study recruited 462 parents residing in the UAE using convenience sampling. Recruitment occurred through various social media platforms including WhatsApp, X, and Instagram, as well as in public by approaching parents in parks and malls. Information collected included …