Medicine and Health Sciences Commons^™

Stereotactic Adaptive Radiation Therapy For Borderline Resectable Or Locally Advanced Pancreatic Cancer To Minimize Gastrointestinal Toxicity (Artia-Pancreas): Protocol For A Single-Arm Prospective Trial, Lauren E Henke, Hyun Kim, Eric Laugeman, Steven Kohlmyer, Claire Mccann, Kate Pietrovito, Kenneth Russell, Jennifer Woo, Alex T Price

2020-Current year OA Pubs

BACKGROUND: Computed tomography (CT)-guided online stereotactic adaptive radiotherapy (CT-STAR) allows for ablative radiation doses to be delivered to selected patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) or unresectable pancreatic cancer. However, the use of CT-STAR to deliver an ablative dose to the pancreas while minimizing gastrointestinal (GI) side effects to reduce acute and late toxicity rates compared to historic controls has yet to be prospectively evaluated.

OBJECTIVE: The primary objective of this prospective, single-arm, multicenter phase 2 clinical trial (Adaptive Radiation Therapy Individualized Approach [ARTIA]-Pancreas) is to evaluate the rate of acute grade 3+ GI toxicity …

Upper Extremity Return To Sport Functional Testing: A Systematic Review, Marisa Pontillo, Eric Bellm, Patrick Barber, Matthew L. Gauthier, Casey A. Unverzagt, George J. Davies

Physical Therapy Faculty Publications

Background: Upper extremity return to sport (RTS) assessments are not standardized with respect to which metrics to use, if the metrics are appropriate for all populations and levels of competition, and what constitutes good or poor test performance. Subsequently, clinicians may utilize suboptimal metrics to evaluate RTS readiness, or forgo objective criteria altogether. The purpose of this study was to examine the psychometric properties (reliability, agreement/measurement error, hypothesis testing/construct validity, criterion/predictive validity, responsiveness) of upper extremity functional tests used to assess RTS readiness.

Methods: This systematic review followed PRISMA guidelines, with all studies included assessed via the PEDro scale. Literature …

Innovative Approaches For Lung Cancer Screening And Interception, Jianjun Zhang, Matthew D Park, Tej Pandya, Elaine Shum, Jia Wu, Simon Heeke, Ramin Salehi-Rad, Thomas U Marron, Zhubo Wei, Hui Li, Torsten G Blum, John V Heymach, Steven M Dubinett, Pan-Chyr Yang, Charles Swanton, Miriam Merad

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

Direct Synthesis Of Bicyclo[1.1.1]Pentane (Bcp) Boronates From Carboxylic Acids, Yongchen Wang, Jess C Tang, Gang Wu, Julian G West

Faculty, Staff and Student Publications

Bicyclo[1.1.1]pentane (BCP) boronic esters are crucial intermediates for accessing BCP-containing drugs with improved pharmacokinetic profiles, yet their synthesis typically relies on pre-formed redox-active esters derived from carboxylic acids. Here we report a general, single-step method for the direct conversion of carboxylic acids into BCP boronic esters. Upon irradiation of carboxylic acids with [1.1.1]propellane and bis(pinacolato)diboron (B2pin2) in dimethyl sulfoxide (DMSO), BCP boronates are obtained in good yields, which are further enhanced by the addition of an iron catalyst. Mechanistic studies suggest that photolytic cleavage of a B2pin2–DMSO complex initiates decarboxylation via hydrogen atom transfer (HAT), while iron catalysis enables a …

Author Correction: Machine Learning Models Predict Long Covid Outcomes Based On Baseline Clinical And Immunologic Factors, Naresh Doni Jayavelu, Hady Samaha, Sonia Tandon Wimalasena, Annmarie Hoch, Jeremy P Gygi, Gisela Gabernet, Al Ozonoff, Shanshan Liu, Carly E Milliren, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Joanna Schaenman, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuit, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Linda N Geng, Ana Fernandez Sesma, Viviana Simon, Florian Krammer, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Charles R Langelier, Impacc Network, Leying Guan, Holden T Maecker, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman

Faculty, Staff and Students Publications

This corrects the article "Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors", 1.

Cerebral Hypoperfusion Causes Behavioral Changes And Impairs The Rod Photoreceptor Pathway In The Retina Of Aged Mice, Spencer Talmage Barney, Daniela Becerril, Sheelu Monga, Samantha Flores, Audrey Lee, Marlon Fraga Mattos, Ross M Perez, Frank W Blixt, Michael Maniskas, Shuning Huang, Hongyu Wu, Chunfeng Tan, Louise D Mccullough, Elizabeth Zuniga-Sanchez, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Gradual reduction of cerebral blood flow occurs with aging, and it is a major cause of vascular dementia, a group of dementias with a cerebrovascular component. Interestingly, patients who have suffered a vascular insult may develop retinopathy, which may occur as an early symptom of vascular dementia. Several rodent models using young animals have been generated to mimic retinopathy caused by cerebral hypoperfusion; however, given that aging is an important factor in developing vascular dementia and hypoperfusion retinopathy, we propose to use aged (17-month-old) mice in a model of cerebral hypoperfusion. In this model, we implant two metallic micro-coils (0.16 …

Trends In Self-Reported Responses To Nutrition Facts Labels Before And After Nutrition Labeling Policy Implementation: A Comparison Of Adults In The United States And Mexico, Jim Thrasher Ph.D., Ma, Ms, Victor Vilalobos, Dai Fang, Alejandra Jáuregui, Alejandra Contreras-Manzano, Rachel Davis Ph.D., Lana Vanderlee, Christine M. White, Rachel B. Acton, James W. Hardin, Edward A. Frongillo Jr. Ph.D., Simón Barquera, David Hammond

Faculty Publications

Background

Objectives

Methods

Strain-Level Heterogeneity In Gardnerella Urinary Tract Persistence And Pathogenesis In An In Vivo Model Is Consistent With Comparative Phylogenomic Analyses, Lokesh Kumar, Sonia N Whang, Deborah K Verges, Robert F Potter, Nicole M Gilbert

2020-Current year OA Pubs

BACKGROUND: Gardnerella is a bacterial genera commonly present in the female urogenital tract, especially in bacterial vaginosis. Gardnerella are frequently detected in urine collected directly from the bladder and have been implicated in urinary incontinence and recurrent urinary tract infections. Understanding the contribution of Gardnerella to pathogenesis is complicated by its genetic heterogeneity and a shortage of data from in vivo models. One clinical isolate of Gardnerella triggered urothelial exfoliation and promoted urinary tract infection by uropathogenic E. coli in a mouse model. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with …

Advances In Hpv Vaccination In People Living With Hiv: A Review, Megan Mooberry, J Brooks Jackson, Mary B Rysavy

Faculty, Staff and Student Publications

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living with HIV (PLWH). PLWH experience a disproportionate burden of HPV-related infection and HPV-related malignancies. Although HPV vaccines have been shown to be highly effective, vaccination coverage among PLWH remains suboptimal, particularly in low- and middle-income countries. Barriers to vaccination include extended dosing schedules, limited awareness of the vaccine, and misinformation. Evidence indicates HPV vaccines are safe and …

Airway Secretory Cells Contain Both A Perinuclear Golgi Ribbon And Dispersed Golgi Satellites, Oanh N Hoang, Colin E Chan, Joshua M Brenner, Denisse Leza-Rincon, Ana M Jaramillo, Brendan Dolan, Adam W Aziz, Rodolfo A Cardenas, Gerardo J Cardenas, Eduardo D Galvez, Joshua B Hales, Emilia S Nunez-Pena, Boxuan Yang, Reid T Powell, Leoncio Vergara, Harry Karmouty-Quintana, Jesper M Magnusson, Gunnar C Hansson, Roberto Adachi, John D Dickinson, Christopher M Evans, Justin A Courson, Alan R Burns, Michael J Tuvim, Burton F Dickey

Faculty, Staff and Student Publications

Rationale: Finely tuned production and secretion of the polymeric mucins MUC5AC and MUCB are required for lung health, but knowledge of many details between their translation and their packaging into secretory granules is lacking.

Objective: To analyze the structure and function of the Golgi apparatus, a key site of mucin glycosylation, folding, polymerization and packaging, in airway epithelial secretory cells.

Methods: Lung tissue was obtained from mice stimulated or not with IL-13 to upregulate mucin production, and from normal human lungs. Golgi elements in mouse and human tissue were imaged by high-resolution immunofluorescence microscopy and electron microscopy. Tissue from mice …

Project Score Program Manual, M. Barnard, T. Johnson, A. Ford-Wade, M. Godfrey, C. Compretta, E. Dehon, S. Nasruddin, B. Wade, W. Sparkmon, M. Presley, A. Jones-White, W. Qualen

Faculty and Student Publications

Project SCORE (student-centered outcomes research experience) is an NIH-funded year-long informal public health education program and mentored research experience utilizing a youth participatory action research (YPAR) approach and near-peer mentors (NPMs) to increase science engagement, interest in college participation, and contribute to a diverse and community-engaged health sciences pipeline.

Integrating Zotero With Your Writing: From Research To Publication For Urology Residency Program, Evelyn Wang

HSLIC Faculty and Staff Instructional Resources

This Urology Residency workshop introduces practical skills for integrating Zotero into research and writing workflows, from managing references to generating citations and bibliographies. Topics include installing and configuring Zotero and the Zotero Connector, collecting and organizing references with collections, tags, and PDFs, inserting citations and bibliographies in Microsoft Word and Google Docs, managing PDFs and annotations, and using advanced features such as sync, collaboration, custom citation styles, and ZoteroBib.

Genetic Modifiers Of Apoe-Ε4-Associated Cognitive Decline, Alex G Contreras, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. …

Human Microglia In Brain Assembloids Display Region-Specific Diversity And Respond To Hyperexcitable Neurons Carrying Scn2a Mutation, Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A Deming, Yue Shu, Akila D Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

The Brown Foundation: Institute of Molecular Medicine

Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABAB receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to activate …

Association Between Children’S Secondhand Co-Exposure To Tobacco And Cannabis Smoke And Elevated Urinary Cotinine Levels: A Cross-Sectional Analysis, Bradley N. Collins, Stephen J. Lepore, Vincent Berardi, Renee D. Goodwin, Karen Wilson, Mona Baishya

Psychology Faculty Articles and Research

Background Cannabis use is far more common among adults who smoke tobacco than adults who do not, and its use is increasing among people who smoke tobacco with children living in the home. Given the well-established evidence that caregiver smoking is the primary source of children’s secondhand exposures to these products, the increasing trend in caregiver co-use is raising public health concerns about children’s co-exposure. Emerging data indicates that adult co-use is linked to additive health consequences, such as elevated nicotine and other tobacco-related toxicant blood levels, relative to use of only tobacco. It is unknown whether children’s co-exposure leads …

Perinatal And Maternal Outcomes By Indication For Delivery In The Second Trimester, Kristen A Cagino, Paula L Mcgee, Maged M Costantine, Michael W Varner, Alan T N Tita, Monica Longo, Barbara J Stoll, John M Thorp, Uma M Reddy, William A Grobman, Dwight J Rouse, Hyagriv N Simhan, Jennifer L Bailit, Lorraine Dugoff, George R Saade, Baha M Sibai

Faculty, Staff and Student Publications

Perinatal and maternal morbidity in the setting of preterm birth may differ by delivery indication. We compared perinatal and maternal outcomes of second-trimester (240/7-276/7 weeks of gestation) deliveries indicated for preeclampsia with severe features (PE-SF), with those following preterm premature rupture of membranes (PPROM).Secondary analysis of an observational cohort study of singleton and twin preterm deliveries before 35 weeks' gestation at 33 hospitals across the United States. Singletons without congenital anomalies who were delivered due to PE-SF or PPROM from 240/7 to 276/7 weeks of gestation were included. The primary outcome was a composite of perinatal morbidity or death, defined …

Dasatinib Resensitizes Braf/Mek Inhibitor Efficacy In Patient-Derived Xenografts From Patients With Progression On Braf/Mek Inhibitor Treatment, Vito W Rebecca, Min Xiao, Andrew Kossenkov, Tetiana Godok, Gregory Schuyler Brown, Dylan Fingerman, Gretchen M Alicea, Meihan Wei, Hongkai Ji, Marie Portuallo, Jeremy Bravo, Vissy Elad, Yeqing Chen, Eneda Toska, Mitchell E Fane, Kasey L Couts, Jessie Villanueva, Katherine Nathanson, Keerthana M Arun, Govind Warrier, Xiangfan Yin, Jianyi Ding, Qin Liu, Yogesh Goyal, Y N Vashisht Gopal, Michael A Davies, Meenhard Herlyn

Faculty, Staff and Student Publications

Although BRAF/MEK inhibitor (BRAFi/MEKi) therapy initially shows high efficacy in patients with BRAFV600 E/K cutaneous melanoma, resistance develops in over 75% of cases. We tested robustness of the umbrella trial strategy in this population by analyzing relationships between genomic status of a gene and associated downstream consequences at the protein level. The results revealed weak relationships among mutations, copy-number amplification, and protein expression and activation. An in vivo compound repurposing screen using 11 clinically relevant agents from an NCI-portfolio with pan-RTK, non-RTK, and/or PI3K-mTOR specificity identified dasatinib as most capable of restoring sensitivity to BRAFi/MEKi in patient-derived xenograft (PDX) …

External Validation Of The Proliferation Saturation Index Model In Predicting Tumour Volume Regression In Patients With Non-Small Cell Lung Cancer Undergoing Radiation Therapy, Sarah Barrett, Mohammad Zahid, Conor K Mcgarry, Heiko Enderling, Gerard M Walls, Laure Marignol

Faculty, Staff and Student Publications

Background: The Proliferation Saturation Index (PSI) model is a patient-specific mathematical model designed to simulate and predict tumour volume regression (TVR) during radiation therapy (RT) using early treatment response dynamics. This study validates the PSI model in an independent external cohort of patients with non-small cell lung cancer (NSCLC) using previously derived model parameters.

Methods: In a cohort of 71 patients, treated with definitive RT alone (55Gy/20#) tumour volume measurements extracted from 6 Cone Beam CT (CBCT) scans acquired on days 1, 2 and 3 and weekly thereafter. Model predictions of TVR at final CBCT (CBCT6) were made using tumour …

Hp1Β Recruits Ring1a To Ubiquitinate Histone H2a For Brca1-Mediated Resection Of Double-Stand Breaks, Vijaya Charaka, Raj K Pandita, Chi-Lin Tsai, Xiaoyan Wang, Sharmista Chakraborty, Kenneth S Ramos, Sandhik Nandi, Fransisca Leonard, Vipin Singh, Partha S Sarkar, Clayton R Hunt, John A Tainer, Chandrima Das, Tej K Pandita

Faculty, Staff and Student Publications

Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Improving Structured Handoff Documentation In A Pediatric Emergency Department, Deborah Hammett, Rebecca Matta, Jody Kieffer, Jillian Savage, Courtney Nelson

Department of Pediatrics Faculty Papers

INTRODUCTION: The I-PASS handoff tool guides provider handoffs and reduces adverse events in the inpatient setting. Transitions of care occur frequently in the emergency department (ED), and the unpredictable environment can lead to less structured handoffs. Our goal was to increase the percentage of handoff notes that include all 4 I-PASS components by 20% within 6 months.

METHODS: We developed a handoff note template for the pediatric ED that included 4 key I-PASS elements: illness severity, patient care summary, action list, and situational awareness/contingency planning. Our primary outcome measure was the percentage of handoff notes that contained all 4 I-PASS …

Steroid Receptor Coactivators - From Basic Research To Translational Opportunities, Yosef Gilad, Sang Jun Han, David M Lonard

Faculty, Staff and Students Publications

The concept of nuclear receptor (NR) coregulation was proposed nearly two decades before it was experimentally validated. According to this model, NRs - executors of a vast array of transcriptional programs - do not act independently but are governed by a network of regulatory proteins that either activate or repress their biological function. NRs identify the genes to be regulated. However, coregulators ultimately serve as the true controllers of transcriptional outcomes. They recruit cofactors and coordinate the activity of transcriptional complexes, thereby shaping NR-mediated gene expression beyond NRs' intrinsic functionality. The Steroid Receptor Coactivator (SRC) family is the most extensively …

Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 inhibits synovial macrophage (SM) activation via xanthine oxidase (XO) and hypoxia inducible factor alpha (HIF-1α) suppression. We aimed to evaluate the contribution of PRG4-CD44 interaction to synovial homeostasis and investigate PRG4’s signaling dysfunction in synovial tissues from patients with osteoarthritis (OA). We hypothesized that CD44 mediates synovitis due to PRG4 loss and that PRG4 signaling dysfunction is associated with high-grade synovitis in OA.

Methods

Prg4^{FrtloxP/FrtloxP} are transgenic mice wherein tamoxifen (TAM) inactivates the Frt allele and creates a knockout state (Prg4^{FrtKO/FrtKO …}

A Phenomenological Approach To Spastic Movement Disorders: An International Expert Panel Consensus, Bo Biering-Sørensen, Jörg Wissel, Raymond Rosales, Rajiv Reebye, Jorge Jacinto, Gerard E Francisco, Peter Sanderson, Per Ertzgaard

Faculty, Staff and Student Publications

Background and objectives: Hyperkinetic movement disorders, characterized by complex and overlapping motor patterns, present significant challenges in classification and treatment. The inconsistency in definitions and descriptors complicates both research and clinical communication. This study aims to provide an overview of current terminology and definitions related to spasticity and other hyperkinetic movement disorders associated with central nervous system lesions. We propose a unified terminology and classification system for spastic movement disorders (SMD).

Methods: In this scoping review, definitions of spasticity, dystonia, tremor, chorea, hemiballismus, athetosis, myoclonus, and dyssynergia were reviewed, with emphasis on overlaps and diagnostic challenges among these disorders. The …

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …

The Neuroprotective Effects Of Alpha-Tocopherol As An Anti-Inflammatory Agent: Mechanistic Insights And Therapeutic Challenges, Megumi H Seese, Yuanzhong Xu

The Brown Foundation: Institute of Molecular Medicine

Vitamin E (alpha-tocopherol, αToc), an antioxidant fat-soluble vitamin that prevents lipid peroxidation and modulates pro-inflammatory cytokine production, is well-known to be critical for neuroprotection. However, the underlying mechanism remains poorly understood. Accumulating evidence demonstrates that αToc influences neuroinflammatory processes. Here, we review recent research progress on the effects of αToc on neuroinflammation. Preclinical studies included in this narrative review were identified through PubMed searches using the keywords "alpha-tocopherol AND neuroinflammation or alpha-tocopherol AND brain AND inflammation". While many studies support a neuroprotective role of αToc, the magnitude and direction of its effects vary substantially depending on dosage, route of administration, …

A Transcriptional Program Associated With Neurotransmission In The Living Human Brain, Alexander W. Charney, Lora E. Liharska, Eric Vornholt, Alissa Valentine, Anina Lund, Alice Hashemi, Ryan C. Thompson, Terry Lohrenz, Jessica S. Johnson, Nicole Bussola, Esther Cheng, You Jeong Park, Salman Qasim, Alisha Aristel, Lillian Wilkins, Kimia Ziafat, Hannah Silk, Lisa M. Linares, Brendan Sullivan, Claudia Feng, Beniamino Hadj-Amar Ph.D.

Faculty Publications

At the foundation of neurotransmission, and by extension at the foundation of brain function, are coordinated programs of gene expression involving many thousands of genes. These programs are poorly defined in humans because most modern studies that characterize human brain gene expression use tissue obtained in the postmortem state when neurotransmission and brain function have ceased. Here, to advance knowledge of the gene expression programs at the foundation of neurotransmission in the human brain, gene expression was characterized in 130 prefrontal cortex (PFC) samples obtained from participants of the Living Brain Project (LBP) during neurosurgical procedures in conjunction with intracranial …

Adipocyte-Specific Deletion Of Sine Oculis Homeobox Homolog 1 Inhibits Lipolysis And Reduces Skin Fibrosis, Nancy Wareing, Tingting W Mills, Scott Collum, Minghua Wu, Lucy Revercomb, René Girard, Hui Liu, Alexes Daquinag, Mikhail Kolonin, Marka Lyons, Brian Skaug, Weizhen Bi, Meer A Ali, Haniyeh Koochak, Anthony R Flores, Yuntao Yang, W Jim Zheng, William R Swindell, Shervin Assassi, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited Systemic sclerosis (SSc) is characterized by dermal fibrosis accompanied by loss of dermal white adipose tissue (DWAT), yet the mechanisms linking adipocyte depletion to fibroblast activation remain unclear. Here we identify the transcription factor SIX1 as a central regulator coupling adipogenic repression with profibrotic signaling. SIX1 expression was increased in skin biopsies from two independent SSc cohorts and localized to fibroblast and perivascular stromal cells. In mice, ubiquitous or adipocyte-specific deletion of Six1 preserved DWAT, reduced collagen accumulation, and selectively decreased pro-fibrotic mediators. In cultured …

Survival On Image Regression With Application To Partially Functional Distributional Representation Of Physical Activity, Rahul Ghosal, Sunwoo Emma Cho, Marcos Matabuena

Faculty Publications

Technological advancements in wearable devices and medical imaging often lead to high-dimensional physiological signals in the form of images or surfaces. To address these data structures, we develop a novel survival on image regression model with a specific focus on partially functional distributional representation of wearable data. The existing approaches for functional data and survival outcomes have been primarily developed for uni-dimensional functional predictors. Drawing on recent developments in distributional data analysis, we model temporally varying distributional patterns of physical activity (PA) as a partially functional distributional predictor within a semiparametric Cox model framework. We use tensor product splines to …