Digital Commons Network^™

Navigating Transition To Adulthood In Epilepsy Patients: A Multidisciplinary Approach., Yinchen Song, L David Klemens, Hallie Orton, Audrey R. Kennedy, Jana E. Jones, Sucheta Joshi, Meghann Kelly

Manuscripts, Articles, Book Chapters and Other Papers

The transition from pediatric to adult healthcare systems is a critical yet complex process for individuals with epilepsy, requiring careful attention to both medical and psychosocial aspects. This review highlights best practices and strategies to facilitate effective transitions, focusing on the roles of multidisciplinary teams, communication strategies, shared decision-making, and transition readiness assessment. Key topics include early and ongoing communication, promoting patient autonomy, addressing mental health comorbidities, and implementing transition readiness assessments such as the Epilepsy Transition Readiness Assessment Questionnaire (EpiTRAQ). Additionally, the review evaluates models for transition clinics, emphasizing the importance of sustainability, collaboration, and tailored interventions. By leveraging …

Legal Issues And Outcomes Of A Medical-Legal Partnership For Cancer Patients, Allison B. Dowling, Abigail Sweeney, Megan E. Gordon, Lisa Kessler, Deborah Perry, Vicki W. Girard, Shreya Kalra

Georgetown Law Faculty Publications and Other Works

The medical-legal partnership (MLP) model is a multidisciplinary intervention with demonstrated success in addressing health-harming legal needs. We analyzed initial data from the Georgetown University Health Justice Alliance’s Cancer Legal Assistance and Well-being Project (Cancer LAW), an MLP between Georgetown University and MedStar Health serving cancer patients receiving care at an urban, safety-net hospital in Washington, D.C. The sample included 81 patients, who had an average of two legal issues, most commonly in the areas of Social Security, estate planning, housing, and health insurance. Data collected during legal representation captured both financial and non-financial benefits to patients. Patients who responded …

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …

Cross-Tissue Coordination Between Slc Nucleoside Transporters Regulates Reproduction In Caenorhabditis Elegans, Youchen Guan, Yong Yu, Shihong M Gao, Lang Ding, Qian Zhao, Meng C Wang

Faculty, Staff and Students Publications

Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Tau Depletion Diminishes Vascular Amyloid-Related Deficits In A Mouse Model Of Cerebral Amyloid Angiopathy, Nur Jury-Garfe, Enrique Chimal-Juárez, Henika Patel, Jonathan Martinez-Pinto, Kathryn Vanderbosch, Muriel D Mardones, Abigail Perkins, Gonzalo Viana Di Prisco, Yamil Marambio, Ruben Vidal, Brady K Atwood, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Introduction: Tau is essential for amyloid beta (Aβ)-induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral amyloid angiopathy (CAA), a major vascular contributor to cognitive decline, affects over 90% of patients with AD. This study explores the impact of tau downregulation on CAA pathogenesis.

Methods: We crossed the Familial Danish Dementia mouse model (Tg-FDD), which develops vascular amyloid, with tau-null (mTau-/-) mice to generate a CAA model lacking endogenous tau (Tg-FDD/mTau-/-). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed.

Results: Tau depletion ameliorated motor and synaptic impairments, reduced vascular amyloid deposition, and prevented …

Recommendations For Design, Execution, And Reporting Of Studies On Experimental Thoracic Aortopathy In Preclinical Models, Alan Daugherty, Dianna M Milewicz, David A Dichek, Ketan B Ghaghada, Jay D Humphrey, Scott A Lemaire, Yanming Li, Ziad Mallat, Yvan Saeys, Hisashi Sawada, Ying H Shen, Toru Suzuki, Zhen Zhou

Faculty, Staff and Students Publications

There is a recent dramatic increase in research on thoracic aortic diseases that includes aneurysms, dissections, and rupture. Experimental studies predominantly use mice in which aortopathy is induced by chemical interventions, genetic manipulations, or both. Many parameters should be deliberated in experimental design in concert with multiple considerations when providing dimensional data and characterization of aortic tissues. The purpose of this review is to provide recommendations on guidance in (1) the selection of a mouse model and experimental conditions for the study, (2) parameters for standardizing detection and measurements of aortic diseases, (3) meaningful interpretation of characteristics of diseased aortic …

Genetics, Manifestations, And Management Of Catecholaminergic Polymorphic Ventricular Tachycardia, Shubh Desai, Oliver M Moore, Xander H T Wehrens

Faculty, Staff and Students Publications

Purpose of review: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating heritable channelopathy that can lead to sudden cardiac death in children and young adults. This review aims to explore genetics, the cardiac and extracardiac manifestations of mutations associated with CPVT, and the challenges involved with managing phenotypically variable variants.

Recent findings: The understanding of the genetics and mechanisms of CPVT continues to grow with recent discoveries including alternative splicing of cardiac TRDN and calmodulin gene variants. Additionally, there is an increasing recognition of the extra-cardiac manifestations such as epilepsy, neurodevelopmental delay, and glucose homeostasis abnormalities in RyR2 variant carriers. …

Multidisciplinary Care In Body Contouring: An Integrative Approach To Enhancing Outcomes, Jacob Dinis, Sofia C Perez Otero, Diego M Quirarte, Winston R Owens, Sebastian J Winocour

Faculty, Staff and Students Publications

Body contouring procedures have become increasingly common to meet the growing demand for aesthetic surgery, particularly in the context of bariatrics. Massive weight loss (MWL) patients are complex and often require extensive management of comorbidities, malnutrition status, physical debilitation, and psychological sequelae. Patient optimization prior to body contouring surgery in addition to strict postoperative maintenance are crucial to achieve favorable and sustainable outcomes. Surgical candidates should be screened thoroughly, and in the MWL patient population specifically, multidisciplinary care is needed for proper evaluation and support. Notable specialists that routinely contribute in MWL and body contouring patient care include plastic surgeons, …

Multidisciplinary Team Care In Plastic Surgery: Vascular Anomalies, Josephine L Schmidt, Vamsi C Mohan, Richard Appel, Tara L Rosenberg, Jessica A Ching

Faculty, Staff and Students Publications

Vascular anomalies consist of a wide range of diagnoses relating to abnormal vasculature. These lesions can affect a variety of anatomical structures, requiring the expertise of numerous specialists. Over the past few decades, the formation of multidisciplinary vascular anomalies clinics has allowed patients to meet multiple providers within the same clinic visit, leading to improved communication between patients and providers. Furthermore, diagnostic and treatment plans are discussed in multidisciplinary conferences allowing for enhanced diagnostic accuracy and more comprehensive management plans. The purpose of this article is to provide an overview of the multidisciplinary management of vascular anomalies, including descriptions of …

Goal Attainment In Pmm2-Cdg: A New Approach Measuring Meaningful Clinical Outcomes, Sanne Verberkmoes, Gina L Mazza, Andrew C Edmondson, Fernando Scaglia, Seishu Horikoshi, Bryce Kuschel, Mirian C H Janssen, Jehan Mousa, Austin Larson, Rameen Shah, Georgia Mcdonald, Kyriaki Sarafoglou, Gerard Berry, Tamas Kozicz, Christina Lam, Eva Morava

Faculty, Staff and Students Publications

Patient-centered outcomes, including patient-reported outcomes (PROs), are increasingly important in healthcare and research, though their use in rare diseases remains limited. In disorders with significant phenotypic variation, selecting appropriate outcome measures is crucial to ensuring the relevance of clinical trials for the patient population. Phosphomannomutase 2-CDG (PMM2-CDG) involves a complex genotype-phenotype relationship, making it challenging to predict clinical outcomes and select reliable measures for clinical trials. Caused by biallelic pathogenic variants in the PMM2, PMM2-CDG displays highly variable clinical severity, underscoring the need for personalized outcome measures. One such so far unexplored, individualized approach is Goal Attainment Scaling (GAS), which …

A Multidisciplinary Approach To Brachial Plexus Birth Injury: An Overview And Institutional Experience, Winston R Owens, Vamsi C Mohan, Diego M Quirarte, John D Bovill, Gabrielle T Nguyen, James H Northcutt Ii, Jenny Lee Nguyen, William C Pederson

Faculty, Staff and Students Publications

Without early diagnosis and intervention, brachial plexus birth injuries (BPBIs) can result in permanent upper extremity debilitation. Previously, BPBI was treated by single-specialty surgeons; however, given the complexity of the injury, BPBIs necessitate multidisciplinary team care. Common specialists involved within brachial plexus injury clinics include radiologists, physical medicine and rehabilitation physicians, occupational therapists, nerve surgeons, and shoulder surgeons. Care plans are meticulously designed by all team members, and depending on injury severity and clinical course, patients may undergo treatment including range-of-motion exercises, splinting, botulinum toxin injections, nerve surgery, or shoulder surgery. The objective of this article is to highlight and …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Expert Consensus For Key Components Of A High-Quality Ventral Hernia Repair Operative Note, Jonathan S Lall, Said Maldonado, Nicole B Lyons, Gina Adrales, Karla Bernardi, Anne P Ehlers, Hobart Harris, Julie Holihan, William Hope, Jeffrey E Janis, Michele Loor, Clayton Petro, Luke Putnam, Caroline E Reinke, John Scott Roth, Christopher Senkowski, Kendell Sowards, Shirin Towfigh, Daniel Dante Yeh, Zuhair Ali, Mike K Liang

Faculty, Staff and Students Publications

Background: Ventral hernia repair (VHR) is one of the most commonly performed procedures by surgeons; however, there remains a lack of consensus for key components of operative reporting. Prior literature has identified several key elements that are recommended for inclusion in ventral hernia repair operative notes, but it is unclear whether these details alone make for a high-quality operative note. This study sought to determine whether experts agree on what factors make a ventral hernia repair operative note high-quality.

Study design: A prospective exploratory sequential survey-based mixed-methods design was used for round 1. Conclusions via thematic analysis from survey responses …

User Actions Within A Clinical Decision Support Alert For The Management Of Hypertension In Chronic Kidney Disease, Lipika Samal, Sarah W Chen, Stuart Lipsitz, Heather J Baer, John L Kilgallon, Michael Gannon, Ryan Dunk, Weng Ian Chay, Richard Fay, Michael Sainlaire, Chenxi Gao, Matthew Wien, Pamela M Garabedian, Edward Wu, Hojjat Salmasian, David W Bates, Patricia C Dykes, Adam Wright, Allison B Mccoy

Faculty, Staff and Students Publications

This study aimed to examine user actions within a clinical decision support (CDS) alert addressing hypertension (HTN) in chronic kidney disease (CKD).A pragmatic randomized controlled trial of a CDS alert for primary care patients with CKD and uncontrolled blood pressure included prechecked default orders for medication initiation or titration, basic metabolic panel (BMP), and nephrology electronic consult (e-consult). We examined each type of action and calculated percentages of placed and signed orders for subgroups of firings.There were firings for medication initiation (813) and medication titration (430), and every firing also included orders for nephrology e-consult (1,243) and BMP (1,243). High …

Macrophage-Mediated Il-6 Signaling Drives Ryanodine Receptor-2 Calcium Leak In Postoperative Atrial Fibrillation, Joshua A Keefe, Yuriana Aguilar-Sanchez, J Alberto Navarro-Garcia, Isabelle Ong, Luge Li, Amelie Paasche, Issam Abu-Taha, Marcel A Tekook, Florian Bruns, Shuai Zhao, Markus Kamler, Ying H Shen, Mihail G Chelu, Na Li, Dobromir Dobrev, Xander Ht Wehrens

Faculty, Staff and Students Publications

Postoperative atrial fibrillation (poAF) is AF occurring days after surgery, with a prevalence of 33% among patients undergoing open-heart surgery. The degree of postoperative inflammation correlates with poAF risk, but less is known about the cellular and molecular mechanisms driving postoperative atrial arrhythmogenesis. We performed single-cell RNA-seq comparing atrial nonmyocytes from mice with and without poAF, which revealed infiltrating CCR2+ macrophages to be the most altered cell type. Pseudotime trajectory analyses identified Il-6 as a gene of interest driving in macrophages, which we confirmed in pericardial fluid collected from human patients after cardiac surgery. Indeed, macrophage depletion and macrophage-specific Il6ra …

Cdc’S Core Elements To Promote Diagnostic Excellence, Daniel J Morgan, Hardeep Singh, Arjun Srinivasan, Andrea Bradford, L Clifford Mcdonald, Preeta K Kutty

Faculty, Staff and Students Publications

Nearly a decade after the National Academy of Medicine released the "Improving Diagnosis in Health Care" report, diagnostic errors remain common, often leading to physical, psychological, emotional, and financial harm. Despite a robust body of research on potential solutions and next steps, the translation of these efforts to patient care has been limited. Improvement initiatives are still narrowly focused on selective themes such as diagnostic stewardship, preventing overdiagnosis, and enhancing clinical reasoning without comprehensively addressing vulnerable systems and processes surrounding diagnosis. To close this implementation gap, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of …

Interventions To Improve Timely Cancer Diagnosis: An Integrative Review, Mark L Graber, Bradford D Winters, Roni Matin, Rosann T Cholankeril, Daniel R Murphy, Hardeep Singh, Andrea Bradford

Faculty, Staff and Students Publications

Cancer will affect more than one in three U.S. residents in their lifetime, and although the diagnosis will be made efficiently in most of these cases, roughly one in five patients will experience a delayed or missed diagnosis. In this integrative review, we focus on missed opportunities in the diagnosis of breast, lung, and colorectal cancer in the ambulatory care environment. From a review of 493 publications, we summarize the current evidence regarding the contributing factors to missed or delayed cancer diagnosis in ambulatory care, as well as evidence to support possible strategies for intervention. Cancer diagnoses are made after …

Feasibility And Acceptability Of The Team Pilot Trial With African American And Latino Families, Ashley M Butler, Marisa E Hilliard, Krystal Christopher, Marissa Baudino, Charles Minard, Lefkothea Karaviti

Faculty, Staff and Students Publications

Objective: We adapted the empirically supported Family Teamwork intervention protocol to support collaborative parent involvement in type 1 diabetes (T1D) management among African American and Latino parents of children with T1D. This randomized pilot study aimed to evaluate feasibility and acceptability of the Type 1 Diabetes Empowerment and Management (TEAM) intervention.

Methods: African American and Latino parents (n = 59; 65% recruitment rate) of youth (ages 5-10 years, M = 8.9 ± 1.6 years; 59% female, M hemoglobin A1c 9.0% ± 1.9%) with diabetes duration of ≥1 year and who were fluent in English and not planning to leave the …

Digital Twins, Synthetic Patient Data, And In-Silico Trials: Can They Empower Paediatric Clinical Trials?, Mohan Pammi, Prakesh S Shah, Liu K Yang, Joseph Hagan, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Randomised controlled trials are the gold standard to assess the effectiveness and safety of clinical interventions; however, many paediatric trials are discontinued early due to challenges in patient enrolment. Hence, most paediatric clinical trials suffer from lack of adequate power. Additionally, trials are expensive and might expose patients to unproven therapies. Alternatives to overcome these issues using virtual patient data—namely, digital twins, synthetic patient data, and in-silico trials—are now possible due to rapid advances in digital health-care tools and interventions. However, such digital innovations have been rarely used in paediatric trials. In this Viewpoint, we propose using virtual patient data …

Challenges And Opportunities Of Acquiring Cortical Recordings For Chronic Adaptive Deep Brain Stimulation, Jeffrey Herron, Aura Kullmann, Timothy Denison, Wayne K Goodman, Aysegul Gunduz, Wolf-Julian Neumann, Nicole R Provenza, Maryam M Shanechi, Sameer A Sheth, Philip A Starr, Alik S Widge

Faculty, Staff and Students Publications

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex. Yet capturing those markers requires the placement of cortex-optimized electrodes in addition …

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Methods

Results

Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed …

Psychiatric Genetics In The Diverse Landscape Of Latin American Populations, Estela M Bruxel, Diego L Rovaris, Sintia I Belangero, Gabriela Chavarría-Soley, Alfredo B Cuellar-Barboza, José J Martínez-Magaña, Sheila T Nagamatsu, Caroline M Nievergelt, Diana L Núñez-Ríos, Vanessa K Ota, Roseann E Peterson, Laura G Sloofman, Amy M Adams, Elinette Albino, Angel T Alvarado, Diego Andrade-Brito, Paola Y Arguello-Pascualli, Cibele E Bandeira, Claiton H D Bau, Cynthia M Bulik, Joseph D Buxbaum, Carolina Cappi, Nadia S Corral-Frias, Alejo Corrales, Fabiana Corsi-Zuelli, James J Crowley, Renata B Cupertino, Bruna S Da Silva, Suzannah S De Almeida, Juan F De La Hoz, Diego A Forero, Gabriel R Fries, Joel Gelernter, Yeimy González-Giraldo, Eugenio H Grevet, Dorothy E Grice, Adriana Hernández-Garayua, John M Hettema, Agustín Ibáñez, Iuliana Ionita-Laza, Maria Claudia Lattig, Yago C Lima, Yi-Sian Lin, Sandra López-León, Camila M Loureiro, Verónica Martínez-Cerdeño, Gabriela A Martínez-Levy, Kyle Melin, Daniel Moreno-De-Luca, Carolina Muniz Carvalho, Ana Maria Olivares, Victor F Oliveira, Rafaella Ormond, Abraham A Palmer, Alana C Panzenhagen, Maria Rita Passos-Bueno, Qian Peng, Eduardo Pérez-Palma, Miguel L Prieto, Panos Roussos, Sandra Sanchez-Roige, Hernando Santamaría-García, Flávio M Shansis, Rachel R Sharp, Eric A Storch, Maria Eduarda A Tavares, Grace E Tietz, Bianca A Torres-Hernández, Luciana Tovo-Rodrigues, Pilar Trelles, Eva M Trujillo-Chivacuan, Maria M Velásquez, Fernando Vera-Urbina, Georgios Voloudakis, Talia Wegman-Ostrosky, Jenny Zhen-Duan, Hang Zhou, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Paola Giusti-Rodríguez, Janitza L Montalvo-Ortiz

Faculty, Staff and Students Publications

Psychiatric disorders are highly heritable and polygenic, influenced by environmental factors and often comorbid. Large-scale genome-wide association studies (GWASs) through consortium efforts have identified genetic risk loci and revealed the underlying biology of psychiatric disorders and traits. However, over 85% of psychiatric GWAS participants are of European ancestry, limiting the applicability of these findings to non-European populations. Latin America and the Caribbean, regions marked by diverse genetic admixture, distinct environments and healthcare disparities, remain critically understudied in psychiatric genomics. This threatens access to precision psychiatry, where diversity is crucial for innovation and equity. This Review evaluates the current state and …

Establishing A Peritoneal Dialysis Technique Survival Core Outcome Measure: A Standardised Outcomes In Nephrology-Peritoneal Dialysis Consensus Workshop Report, Emma H Elphick, Karine E Manera, Andrea K Viecelli, Jonathan C Craig, Yeoungjee Cho, Angela Ju, Jenny I Shen, Martin Wilkie, Samaya Anumudu, Neil Boudville, Josephine Sf Chow, Simon J Davies, Patricia Gooden, Tess Harris, Arsh K Jain, Adrian Liew, Andrea Matus-Gonzalez, Noa Amir, Annie-Claire Nadeau-Fredette, Thu Nguyen, Angela Yee-Moon Wang, Daniela Ponce, Rob Quinn, Alison Jaure, David W Johnson, Mark Lambie, Peritoneal Dialysis International

Faculty, Staff and Students Publications

Background

Methods

Results

Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth

Faculty, Staff and Student Publications

Purpose: To evaluate the safety and efficacy of vertebral augmentation (VA) and radiofrequency ablation (RFA) for treating pathologic spinal fractures in patients with cancer and adjacent fracture risk following treatment.

Materials and Methods: This single-institution retrospective study, conducted from January 2017 to September 2020, included patients with cancer who underwent percutaneous VA with or without spine RFA for pathologic spine compression fractures. The primary outcome was pain reduction, assessed using the 10-point visual analog scale before the procedure, at first follow-up, and 2–4 weeks after the procedure. Logistic regression was performed to identify factors associated with epidural cement leak.

Results: …

The Multilayered Transcriptional Architecture Of Glioblastoma Ecosystems, Masashi Nomura, Avishay Spitzer, Kevin C Johnson, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhfury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Roel G W Verhaak, Antonio Iavarone, Mario L Suvà, Itay Tirosh

Faculty, Staff and Student Publications

In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary and recurrent GBM samples from 59 patients using single-nucleus RNA sequencing and bulk tumor DNA sequencing to characterize GBM transcriptional heterogeneity. First, GBMs can be classified by their broad cellular composition, encompassing malignant and nonmalignant cell types. Second, in each cell type we describe the diversity of cellular states and their pathway activation, particularly an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like and cilia-like. Third, the remaining variation between GBMs highlights three baseline gene expression …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

Faculty, Staff and Student Publications

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Glutamate Gating Of Ampa-Subtype Iglurs At Physiological Temperatures, Anish Kumar Mondal, Elisa Carrillo, Vasanthi Jayaraman, Edward C Twomey

Faculty, Staff and Student Publications

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate most excitatory neurotransmission1. iGluRs are gated by glutamate, where on glutamate binding, they open their ion channels to enable cation influx into postsynaptic neurons, initiating signal transduction1,2. The structural mechanics of how glutamate gating occurs in full-length iGluRs is not well understood. Here, using the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype iGluR (AMPAR), we identify the glutamate-gating mechanism. AMPAR activation by glutamate is augmented at physiological temperatures. By preparing AMPARs for cryogenic-electron microscopy at these temperatures, we captured the glutamate-gating mechanism. Activation by glutamate initiates ion channel opening that involves all ion …

Characterization Of Human Senescent Cell Biomarkers For Clinical Trials, Joshua N Farr, David G Monroe, Elizabeth J Atkinson, Mitchell N Froemming, Ming Ruan, Nathan K Lebrasseur, Sundeep Khosla

Faculty, Staff and Students Publications

There is an increasing need for biomarkers of senescent cell burden to facilitate the selection of participants for clinical trials. p16 Ink4a is encoded by the CDKN2A locus, which produces five variant transcripts in humans, two of which encode homologous p16 proteins: p16Inka4a, encoded by p16_variant 1, and p16ɣ, encoded by p16_variant 5. While distinct quantitative polymerase chain reaction primers can be designed for p16_variant 5, primers for p16_variant 1 also measure p16_variant 5 (p16_variant 1 + 5). In a recent clinical trial evaluating the effects of the senolytic combination, dasatinib + quercetin (D + Q), on …