Digital Commons Network^™

Cerebrovascular Risk With Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Onabotulinumtoxina In Patients With Migraine: A Real-World Pharmacoepidemiologic Study In The National Institutes Of Health All Of Us Research Program, Sedat Gül, Bradley Ong, Stephen Trudeau, Nicolas Thompson, Hsiangkuo Yuan

Department of Jefferson Headache Center Papers and Presentations

AimTo evaluate whether initiation of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) was non-inferior to initiation of onabotulinumtoxinA with respect to the hazard of ischemic stroke or transient ischemic attack (IS + TIA) in a real-world cohort of adults with migraine.MethodsWe conducted a retrospective, active-comparator, new-user pharmacoepidemiology study using the NIH All of Us Research Program Registered Tier Dataset (v8). Adults with migraine initiating CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) were compared with initiators of onabotulinumtoxinA from January 2018 through September 2023. The primary outcome was IS + TIA occurring more than 90 days after treatment initiation. Inverse probability of …

Pearson Syndrome: Expanding The Clinical Spectrum Of A Mitochondrial Cytopathy-A Case Report, Alizah Faisal, Hooria Waqas, Hania Masood, Armeen Butt, Saad Rahman, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Ali Iqbal, Muhammad Usama Naveed

Department of Medicine Faculty Papers

BACKGROUND: Pearson syndrome (PS) is a rare multisystem mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions (SLSMDs). It typically presents in infancy with refractory sideroblastic anemia, exocrine pancreatic insufficiency, and failure to thrive. Due to its heterogeneous manifestations and resemblance to other hematological conditions, early diagnosis remains a clinical challenge.

CASE PRESENTATION: A south asian male infant presented with persistent pancytopenia, severe anemia unresponsive to intravenous and oral iron and multivitamin supplements, exocrine pancreatic insufficiency, failure to thrive, and metabolic acidosis. Born to consanguineous parents, the child had a significant family history of early infant deaths and hematological abnormalities. …

Mechanisms Coordinating Exit From The Stem Cell State In Mammals, Emily J Park, Florencia Levin-Ferreyra, Bruno Di Stefano

Faculty, Staff and Students Publications

Differentiation requires coordinated exit from the stem cell state, during which gene regulatory networks sustaining self-renewal are dismantled, while lineage-specific programs are activated. This transition is governed by chromatin modifications, transcriptional networks, RNA processing, translational control, and metabolic rewiring that must operate with temporal precision. Despite significant progress in identifying individual regulatory components, understanding how these layers integrate to orchestrate irreversible cell fate commitment remains a fundamental challenge. This review examines common and unique regulatory principles governing stem cell exit, from totipotency during early embryogenesis to tissue-specific stem cell differentiation in adults. We synthesize recent findings on regulatory mechanisms across …

Current Practices And Variations Among Pediatric Severe Asthma Programs In The United States-The North American Severe Pediatric Asthma Consortium., Kristina Gaietto, Nadia Krupp, Avani V. Shah, Erhan Ararat, Samantha H. Averill, Sachin Baxi, Matejka Cernelc-Kohan, Jeffrey M. Chambliss, Heather De Keyser, Monica Federico, Bob Geng, Akilah A. Jefferson, Parisa Kaviany, Lila C. Kertz, Kirsten Kloepfer, Allyson Larkin, Sydney Leibel, Tanya Martinez-Fernandez, Samira Naime, Robert D. Pesek, Dinesh K. Pillai, Deepa Rastogi, Katherine Rivera-Spoljaric, Kristie R. Ross, Franziska J. Rosser, Tregony C. Simoneau, Jade Tam-Williams, Kelan G. Tantisira, William Anderson, Jonathan M. Gaffin, Theresa W. Guilbert, Erick Forno

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Severe and difficult to treat asthma in children is a complex condition causing significant morbidity and associated healthcare costs. While treatment guidelines exist for severe asthma, optimal treatment approaches for the pediatric population are less well established. Furthermore, best practices regarding real world management and implementation of guidelines for the severe pediatric asthma population are lacking. In order to provide care for this population, institutions around the United States have developed multidisciplinary severe pediatric asthma programs (SPAPs). In recent years, the North American Severe Pediatric Asthma Consortium (NASPAC) was established as a mechanism for SPAPs to collaborate and share …

Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).

METHODS: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were …

A Nationwide Central Diagnosis For Pediatric Cns Tumors In Japan: The Jccg Brain Tumor And Pathology Committees, Yoshiko Nakano, Junko Hirato, Takako Yoshioka, Tetsuya Takimoto, Sumihito Nobusawa, Kaishi Satomi, Ran Tomomasa, Seiji Yamada, Taku Homma, Shoh Sasaki, Ayako Yamazaki, Maki Sakaguchi, Yasuhide Takeuchi, Nei Fukazawa, Kai Yamasaki, Kohei Fukuoka, Yui Shinohara Kimura, Yuki Nagayama, Yohei Inoue, Akira Miyahira, Ema Yoshioka, Asako Katsuma, Hayato Fukusumi, Tomoko Shofuda, Yuko Hibiya, Yuko Matsushita, Mai Honda Kitahara, Yuki Yomoda, Miho Kato, Michael D Taylor, Yasuhito Arai, Tatsuhiro Shibata, Hiroaki Sakamoto, Keita Terashima, Yoshiki Arakawa, Toshihiro Kumabe, Ryo Nishikawa, Junichi Hara, Yonehiro Kanemura, Koichi Ichimura

Faculty, Staff and Students Publications

In 2016, the Japan Children's Cancer Group launched a nationwide research initiative to provide central diagnosis incorporating pathology review and molecular profiling for pediatric central nervous system (CNS) tumors. Over the first eight years, 2224 cases were registered. Non-next-generation sequencing analyzes, such as pyrosequencing and NanoString, were routinely performed, mainly for glioma, medulloblastoma, and ependymoma. Additional analyzes, including methylation profiling and RNA sequencing, were conducted for selected diagnostically challenging cases. The most common diagnoses were low-grade glioma (26%), medulloblastoma (18%), germ cell tumor (16%), high-grade glioma (12%), and ependymoma (11%). Diagnostic or targetable alterations were detected in nearly half of …

Evidence-Based Classification Of Genes Implicated In Skeletal Disorders Using The Clingen Curation Framework, Ryan F Webb, Hannah Mccurry, Amanda Girod, Madeline Hughes, Emma Wilcox, Mayher Patel, Eleanor C Broeren, Kezang C Tshering, Marina Distefano, Lorenzo D Botto, Lindsay C Burrage, Valérie Cormier-Daire, Juan Dong, Nadja Ehmke, Deborah Krakow, Shahida Moosa, Geert Mortier, Sandesh Nagamani, Loren Pena, Pedro A Sanchez-Lara, Andrea Superti-Furga, Sheila Unger, Danita Velasco, Matthew L Warman, Kerry Brown, Deepika D'Cunha Burkardt, Carlos R Ferreira

Faculty, Staff and Students Publications

More than 770 genetic skeletal disorders have been described, most with disease-causing variants reported in 1 of over 550 different genes. The ClinGen Skeletal Disorders Gene Curation Expert Panel was established to determine the strength of the evidence that supports specific gene-disease relationships (GDRs). Such information can assist clinical testing laboratories in choosing genes that should be included on diagnostic panels. Nine genes accounting for the most frequently encountered skeletal dysplasias (COL1A1, COL1A2, COL2A1, FGFR3, SLC26A2, TRPV4, COMP, ALPL, and SOX9) associated in the medical literature with 26 different skeletal disorders were reviewed using a semi-quantitative scoring framework. This framework …

High-Throughput Quantitation Of Pathogen-Induced Calcium Signals Captured Through Live-Cell Fluorescence Microscopy, J Thomas Gebert, Ethan M Huleatt, Francesca J Scribano, Michael R Eledge, Lauren E Dorn, Sammy K Hasmi, Joseph M Hyser

Faculty, Staff and Students Publications

Many intracellular pathogens manipulate host cell calcium to facilitate their survival and replication. Live-cell microscopy using fluorescent calcium indicators has become an indispensable tool for characterizing the mechanisms underlying both homeostatic and pathogen-induced cellular calcium dynamics, but such imaging must be coupled with robust quantitative analysis. Further, calcium imaging is most powerful when paired with reductive studies targeting calcium-modulating proteins. The lack of specific inhibitors or agonists to directly target most pathogen-induced calcium signals precludes many of the approaches that have allowed for robust characterization of major eukaryotic cell calcium signaling mechanisms, such as ER Ca2+ release by inositol triphosphate …

Crispr/Cas9-Based Genome Editing: Understanding Differences In Dna Repair Pathways, Profiles, And Outcomes, Samuel Effah, Shirley Barrera, Nahia Urturi Ortiz, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the …

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

Faculty, Staff and Students Publications

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

Obesity And Keratoconus: A Mediation Study Based On The Chinese Keratoconus Cohort, Kaili Yang, Anqi Chang, Runqi Tu, Liyan Xu, Yuwei Gu, Qi Fan, Shanshan Yin, Yi Yuan, Yifan Wang, Chenchen Yin, Yonghao Zang, Changxiu Li, Chenjiu Pang, Daniela Oehring, Yibin Hao, Shengwei Ren

School of Health Professions

Purpose: Growing evidence indicates a strong association between obesity and keratoconus (KC), although the potential mediating factors remain largely unknown. This study aimed to explore the potential pathways through which corneal biomechanical and topographic parameters might link obesity and KC using structural equation modeling (SEM). Methods: This case-control study included 759 participants (363 patients with KC and 396 controls) from the Chinese Keratoconus (CKC) Cohort Study. Associations among body mass index (BMI), corneal biomechanical parameters, topographic parameters, and KC were analyzed using generalized linear regression models. SEM was used to construct latent variables for corneal biomechanical and topographic parameters. Three …

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

Faculty, Staff and Students Publications

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

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

Intersection Of Pediatric Hypertension And Cardiovascular-Kidney-Metabolic Disease, Jessica O'Keeffe, Christina Kingshill, Jack Tompson, Andrew M. South, Carissa M. Baker-Smith

Department of Medicine Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to describe the intersection between pediatric hypertension and advancing stages of cardiovascular, kidney metabolic syndrome in children and adolescents.

RECENT FINDINGS: Cardiovascular-kidney-metabolic syndrome is highly prevalent in the pediatric population. The onset of CKM in childhood is influenced by the presence of antenatal risk factors such as maternal hypertensive disorders of pregnancy. Advancing stages of CKM in children and adolescents are strongly influenced by food insecurity and social determinants of health that impact the risk for childhood obesity. Activation of the renin-angiotensin-aldosterone system is a key mediator in the relationship between …

Stabilizing And Strengthening The Us Physician-Scientist Faculty Workforce In Academic Medicine: A Proposed Institutional Framework, Christopher S. Williams, Deborah J. Lenschow, Et Al.

2020-Current year OA Pubs

Physician-scientists represent one of the most impactful, yet underrecognized, innovations of 20th century academic medicine. Defined by a commitment to full-time careers in investigative work, physician-scientists have repeatedly demonstrated a unique ability to identify and solve problems of unmet medical need in a focused and intentional manner using their dual training in clinical medicine and the scientific method as both stethoscope and scalpel. Unfortunately, while the value of physician-scientists has never been greater, the institutional infrastructure to support them has never been explicitly defined (1), a deficiency now amplified by mounting financial pressures from both clinical revenue models and an …

The Transitional Liver Clinic: Study Protocol For A Stepped-Wedge Cluster Randomized Trial, Lindsay Yoder, Elliot B. Tapper, Richard S. Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S. Orman

Einstein Health Papers

BACKGROUND: Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.

METHODS: This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention …

Macropinocytosis Inhibition Attenuates Profibrotic Responses In Lung Fibroblasts And Pulmonary Fibrosis Models, Ivan O Rosas, Aaron K Mcdowell-Sanchez, Santiago Sanchez, Juan D Cala-Garcia, Alan R Waich Cohen, Elisa Ruiz-Echartea, Scott A Ochsner, Daniel C Kraushaar, Lindsay J Celada, Dandan Sun, Francesca Polverino, Cristian Coarfa, Neil J Mckenna, Konstantin Tsoyi

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in experimental pulmonary fibrosis models. We found that macropinocytosis is increased in human lung fibroblasts (HLFs) derived from patients with IPF. The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs and reduced pulmonary fibrosis in bleomycin-injured (Bleo-injured) mice. EIPA exerted its antifibrotic effects by regulating amino acid uptake, mammalian target of rapamycin complex 1 …

Gpr182 Is A Lipoprotein Receptor For Dietary Fat Absorption, Zhiwei Sun, Gwendalyn J. Randolph, Et Al.

2020-Current year OA Pubs

The lymphatic system plays a central role in lipid absorption by transporting triglyceride-rich particles called chylomicrons (CMs) from the small intestine to the systemic circulation. However, the molecular mechanism by which CMs get into the intestinal lymphatics is unknown. Here, we demonstrated that GPR182, an atypical chemokine receptor in lymphatic endothelial cells, mediates dietary fat absorption. GPR182-KO mice exhibited a selective increase in circulating high-density lipoproteins and are resistant to diet-induced obesity. GPR182 ablation in mice led to poor lipid absorption and thereby a delay in growth during development. GPR182 broadly interacted with and transported lipoproteins. Transmission electron microscopy analysis …

Identifying Social Determinants Of Health Subgroups And Their Associations With Health Outcomes In A Prospective Us Adult Covid-19 Cohort: An Analysis Of The Inspire Registry, Yohali Burrola-Mendez, Eugene Lin, Canada Parrish, Chialing Hsu, Mandy J. Hill, Michael Gottlieb, Kristin L. Rising, Lauren E. Wisk, Nicole L. Gentile, Rachel E. Geyer, Robert A. Weinstein, Michelle Santangelo, Kristyn Gatling, Jonathan W. Dyal, Joann G. Elmore, Robert M. Rodriguez, Phillip Watts, Ji Chen, Zihan Diao, Erica S. Spatz, Kwun Cg Chan, K A. Stephens, Kelli N. O'Laughlin, Inspire Group

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

DESIGN: Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

SETTING: Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and …

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, Avigail Lithwick Algon, Sarah Brisman, Chi-Ying R Lin, William Saban

Faculty, Staff and Students Publications

Background: Traditional in-person neuropsychological tests for Parkinson disease (PD) lack accessibility, scalability, and PD specificity. Mobility impairments hinder access to in-person assessments, and long waiting times for expert evaluation limit scalability. Common tools for cognitive screening, such as the Montreal Cognitive Assessment, are generic and not specific to PD.

Objective: The goal of this study was to address these challenges by leveraging the internet. This study aimed to develop a sensitive tool to detect cognitive impairments in early- to mid-stage PD in an accessible and scalable manner.

Methods: We developed the Online Rapid Cognitive Assessment for Parkinson's Disease (ORCA-PD), a …

Modeling Immune Responses To Autologous And Allogeneic Human Stem Cell-Derived Islet Grafts In Vivo, Camillo Bechi Genzano, Matthew Ishahak, Enrique Eduardo Sanchez-Castro, Jeffrey R. Millman, Cory Berkland, Et Al.

2020-Current year OA Pubs

Stem cell-derived β cells offer a promising approach for type 1 diabetes (T1D) treatment. However, the processes of graft infiltration and rejection by immune cells remain poorly understood in humans. In this study, autologous or allogeneic stem cell-derived islets (SC-islets) were transplanted in human immune system mice and analyzed 14 to 18 weeks later. Imaging mass cytometry revealed unique characteristics of SC-islet grafts, including a high percentage of glucagon+ cells and the presence of cysts and CD57+ enterochromaffin cells, features not typically observed in endogenous or transplanted allogeneic primary pancreatic islets. Allogeneic SC-islet grafts exhibited heavy immune infiltration, cell proliferation, …

Recommendations For Disclosure Of Artificial Intelligence In Scientific Writing And Publishing: A Regional Anesthesia And Pain Medicine Modified Delphi Study, Michael R Fettiplace, Anuj Bhatia, Yian Chen, Steven L Orebaugh, Michael Gofeld, Rodney A Gabriel, Daniel I Sessler, Hannah Lonsdale, Brittani Bungart, Christopher P Cheng, Garrett W Burnett, Lichy Han, Matthew Wiles, Steve Coppens, Thomas Joseph, Kristin L Schreiber, Thomas Volk, Richard D Urman, Vesela P Kovacheva, Christopher L Wu, Edward R Mariano, Vivian H Y Ip

Faculty, Staff and Student Publications

Introduction: The use of artificial intelligence (AI) in the scientific process is advancing at a remarkable speed, thanks to continued innovations in large language models. While AI provides widespread benefits, including editing for fluency and clarity, it also has drawbacks, including fabricated content, perpetuation of bias, and lack of accountability. The editorial board of Regional Anesthesia & Pain Medicine (RAPM) therefore sought to develop best practices for AI usage and disclosure.

Methods: A steering committee from the American Society of Regional Anesthesia and Pain Medicine used a modified Delphi process to address definitions, disclosure requirements, authorship standards, and editorial oversight …

Monoclonal Antibodies Targeting Pcdh7 Inhibit Tumor Growth And Enhance Immune Responses In Kras-Mutant Non-Small Cell Lung Cancer, Nicole Novaresi, Poorva Ghosh, Shayna Thomas-Jardin, Hui Deng, Xuejun Fan, Zhiqiang Ku, Wei Xiong, Xiaorong Zhou, Jingfei Zhu, Huiyu Li, Mahesh S Padanad, Bethany Smith, Chul Ahn, John D Minna, Zhiqiang An, Ningyan Zhang, Kathryn A O'Donnell

The Brown Foundation: Institute of Molecular Medicine

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors …

Intrathecal Antibody Synthesis - Reiber Method Revisited, John J. Halperin, Dane Granger

Department of Neurology Faculty Papers

BACKGROUND: CSF immunoglobulin (IgG) often informs diagnosis in CNS inflammatory disease- qualitatively (oligoclonal bands; OCBs), or quantitatively (CSF: serum IgG: albumin, e.g. IgG index). Most US laboratories estimate excess CSF IgG using linear models, most in Europe, Reiber's hyperbolic model - the latter often also incorporated into CSF pathogen-specific immunoreactivity calculations. We compared Reiber hyperbolic and linear approaches.

METHODS: Required data were available for 1,872 samples, Lyme-specific data for 1,365. We compared linear and Reiber's hyperbolic models to determine which better describes normal CSF: serum IgG/albumin, assessed correlations with OCBs using ROC analysis and compared Lyme-specific antibody indices (AI) by …

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

Rethinking Ethics For An Era Of Trusted Computational Tools, Kristin M Kostick-Quenet, Meghan Hurley, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Computer perception (CP) technologies are poised to deliver near real-time behavioral insights with high precision. As technical barriers recede, our field's ethical focus must shift from "Can we trust the data?" to "Should we use it here, and how?" We propose a contextual ethics framework that: (1) defines the appropriate scope of CP integration; (2) advocates codesigned roadmaps to manage expectations and epistemic conflict; (3) expands evaluation beyond performance metrics to humanistic outcomes; and (4) anticipates future high performance systems to safeguard dignity, empathy, and shared decision-making in clinical care.

Sex-Based Disparities In Health Care Access And Utilization Among Patients With Atrial Fibrillation, Ji Mei May Wong, Peter R. Kowey

Department of Medicine Faculty Papers

IMPORTANCE: Females with atrial fibrillation (AF) experience a higher risk of stroke, myocardial infarction, and mortality than males with AF. Theories suggest that sex-based differences in hormonal, structural, and electrophysiologic factors are associated with this imbalance; we hypothesized that sex-based differences in health care access and utilization (HCAU) are also underlying factors.

OBJECTIVE: To determine whether sex-based disparities in HCAU barriers exist among individuals with AF.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data on patients with AF in the All of Us Research Program Registered Tier dataset (version 8), which contains integrated data from the electronic health record …

Updated 2026 Comprehensive Evidence-Based Guidelines For Facet Joint Interventions In The Management Of Chronic Spinal Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Laxmaiah Manchikanti, Mahendra R. Sanapati, Sheri L. Albers, Alan D. Kaye, Vinita Singh, Nebojsa Nick Knezevic, Rajesh Naidu Janapala, Amol Soin, Annu Navani, Adam M. Kaye, Ahad Mussarat, Alexander Bautista, Dajie Wang, Paul J. Christo, Maged Mina, Daneshvari R. Solanki, Devi Nampiaparampil, Gerard Limerick, John Manor, Kris Ferguson, Lynn Cintron, Michael Bottros, Shirley Chen, Shivam S. Shah, Vahid Grami, Douglas P. Beall, Shalini Shah, Sairam Atluri, Mittal S. Prajapati, Alaa Abd-Elsayed, Salahadin Abdi, Steve Aydin, Sanjay Bakshi, Joseph Cabaret, Aaron K. Calodney, Kenneth D. Candido, Christopher G. Gharibo, Mayank Gupta, Michael Harned, Standiford Helm Ii, Sachin Sunny Jha, Radomir Kosanovic, Vidyasagar Pampati, Ramarao Pasupuleti, Bradley W. Wargo, Hermant Kalia, Gary Schwartz, Joshua A. Hirsch

Department of Anesthesiology Faculty Papers

BACKGROUND: Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain.

OBJECTIVE: To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions.

METHODS: A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed …

Incidental Colorectal Adenomas In Adolescents: Clinical Management, Genetic Evaluation, And Surveillance., Brett J. Hoskins, Shlomi Cohen, Colleen B. Flahive, Isabel Rojas, Aparajita Singh, Thomas M. Attard

Manuscripts, Articles, Book Chapters and Other Papers

The rising incidence of early-onset colorectal cancer has renewed attention to colorectal adenomas in adolescents and young adults (AYA), although these lesions remain rare and poorly characterized in adolescents. Lack of age-specific guidance creates uncertainty regarding genetic evaluation, surveillance intervals, and long-term management when these lesions are identified in adolescents. This narrative review synthesizes current evidence and expert perspective on epidemiology, evaluation, endoscopic management, surveillance, genetic considerations, and psychosocial implications of incidentally identified colorectal adenomas across the AYA spectrum, with emphasis on adolescents as a distinct clinical population. Available data largely derive from adults aged 20-49 years but suggest that …

The International Glossary On Infertility And Fertility Care, 2025†., Fernando Zegers-Hochschild, Silke Dyer, G David Adamson, Valerie Baker, Kurt Barnhart, Siladitya Bhattacharya, Clare Boothroyd, Georgina Chambers, Jacques De Mouzon, Eman Elgindy, Bart Fauser, Karin Hammarberg, Marcos Horton, Osamu Ishihara, Seung Chik Jwa, Mohamed Khrouf, Markus Kupka, Dolores J. Lamb, Martha Luna, A Gustavo Martinez, Brent Monseur, Peter Nagy, Anja Pinborg, Catherine Racowsky, Laura Rienzi, Peter Schlegel, Lone Schmidt, Lan Ngoc Vuong, Tari Turner, Mónica Hebe Vázquez-Levin, Ibrahim Wada, Dagan Wells, Christine Wyns

Manuscripts, Articles, Book Chapters and Other Papers

STUDY QUESTION: What updates of the International Glossary on Infertility and Fertility Care are required, to reflect contemporary scientific knowledge, social needs, and inclusive definitions, while harmonizing international communication across clinical, research, policy, and public domains?

SUMMARY ANSWER: This 4th edition presents 348 consensus-based terms and definitions, including numerous revisions from the previous edition and 79 newly introduced definitions reflecting advances in reproductive science, technology, and evolving social contexts.

WHAT IS KNOWN ALREADY: Previous glossary editions (2006, 2009, 2017) established internationally recognized definitions related to clinical practice, research, and policy. The 2017 edition comprised 283 terms and, among many others, …

Corneal Innervation Research At A Crossroads: A Tool-Driven Roadmap For The Future, Anna Matynia, Ian D Meng, Brian M Davis, Stephen C Pflugfelder, Anat Galor, Victor L Perez, Elizabeth R Felix, Pedram Hamrah, Pantelimon Rompolas, Raul E Ruiz-Lozano, Shamsuddin A Bhuiyan, Kaveh Moghbeli, Evangelia Semizoglou, William Renthal, Harinder Singh, Jishnu Das, Marcin Golczak, Mary Ann Stepp, Catherine W Morgans, Cintia S De Paiva, Carl Y Saab, Igor Spigelman, Rony R Sayegh, Tally M Largent-Milnes, Hao Wu, Wenqin Luo, Sreya Mitra, Heesuk Yoo, Sina Farsiu, Sejiro Littleton, Eden Jacob, Matthew T Mcpheeters, Maryse Lapierre-Landry, Jordan J Smith, Xi Wang, Roxana Florea, Made Airanthi K Widjaja-Adhi, Scott Holmes, Zane Zemborain, Kate E T Laise, Nicholas J Pondelis, Ki-Soo Jeong, Rui Chen, Michael W Jenkins, Vivian Lee, Eric A Moulton, Deborah S Jacobs, Sue A Aicher, Anthony J St Leger, Daniel R Saban

Faculty, Staff and Students Publications

Corneal innervation research has faced long-standing clinical challenges that only recent technological breakthroughs now make tractable. Advances in single-cell analysis, viral vectors, clinical imaging, and artificial intelligence provide integrated approaches for uncovering molecular mechanisms underlying functional outcomes and facilitating clinical applications. The National Eye Institute's U01-funded consortium on ocular surface innervation addresses major knowledge gaps in characterizing corneal-projecting neurons, understanding neuroimmune and epithelial interactions in the cornea, and translating animal model findings to human pathology. The unique properties of the cornea (transparent, avascular, and densely innervated) make it ideal for neurobiology research on peripheral and central sensory processing. Through a …