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Principles And Practice In Pediatric Vascular Trauma: Part 1: Scope Of Problem, Team Structure, Multidisciplinary Dynamics, And Solutions, Matthew T Harting, Natalie A Drucker, Mary T Austin, Matthew R Greives, Bryan A Cotton, S Keisin Wang, Derrick P Williams, Joseph J Dubose, Charles S Cox

The Brown Foundation: Institute of Molecular Medicine

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For the patients who initially survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and additionally trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly. Vascular injury management demands timely and unique expertise, particularly for pediatric patients. As the frequency of vascular injuries requiring operative management increases, it becomes clear that an ad hoc approach is not ideal. An integrated team would provide …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Rowan Saloner, Jacob W Vogel, Varsha Krish, Gamal Abdel-Azim, Muhammad Ali, Lijun An, Federica Anastasi, David Bennett, Alexa Pichet Binette, Adam L Boxer, Martin Bringmann, Jeffrey M Burns, Carlos Cruchaga, Jeff L Dage, Amelia Farinas, Luigi Ferrucci, Caitlin A Finney, Mark Frasier, Oskar Hansson, Timothy J Hohman, Erik C B Johnson, Mika Kivimaki, Roxanna Korologou-Linden, Agustin Ruiz Laza, Allan I Levey, Inga Liepelt-Scarfone, Lina Lu, Niklas Mattsson-Carlgren, Lefkos T Middleton, Kwangsik Nho, Hamilton Se-Hwee Oh, Ronald C Petersen, Eric M Reiman, Oliver Robinson, Jeffrey D Rothstein, Andrew J Saykin, Artur Shvetcov, Chad Slawson, Bart Smets, Marc Suárez-Calvet, Betty M Tijms, Maarten Timmers, Fernando Vieira, Natalia Vilor-Tejedor, Pieter Jelle Visser, Keenan A Walker, Laura M Winchester, Tony Wyss-Coray, Chengran Yang, Niranjan Bose, Simon Lovestone, The Global Neurodegeneration Proteomics Consortium (Gnpc)

Faculty, Staff and Student Publications

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Associations Between Social Support, Social Control, And Stage Of Change With Self-Reported And Objectively Assessed Physical Activity In Adult Latino Dyads, Jemima C John, Minjae Lee, Soo K Park, Lorna H Mcneill, Deanna M Hoelscher, Susan M Schembre, Belinda M Reininger, Larkin L Strong

Faculty, Staff and Student Publications

Health behaviors such as physical activity (PA) are socially influenced, such that individuals from shared social networks or living environments may exhibit similar habits. This cross-sectional study examined associations of social support, social control, and family member stage of change with moderate-to-vigorous self-reported and objective PA in dyads of adult Hispanic family members. We used the Godin Leisure-Time Physical Activity Questionnaire to assess self-reported PA and accelerometry for objective PA. Validated scales assessed social support, social control, and stage of change. We performed multivariable multilevel analysis using generalized estimating equations (GEE) to account for within-dyad correlations. We conducted multivariable negative …

A Large-Scale Genome-Wide Study Of Gene-Sleep Duration Interactions For Blood Pressure In 811,405 Individuals From Diverse Populations, Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa De Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung Kho, Christophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Botong Shen, Stefan Stadler, Quan Sun, Jingxian Tang, Sébastien Thériault, Adriaan Van Der Graaf, Peter J Van Der Most, Yujie Wang, Stefan Weiss, Kenneth E Westerman, Qian Yang, Tabara Yasuharu, Wei Zhao, Wanying Zhu, Drew Altschul, Md Abu Yusuf Ansari, Pramod Anugu, Anna D Argoty-Pantoja, Michael Arzt, Hugues Aschard, John R Attia, Lydia Bazzanno, Max A Breyer, Jennifer A Brody, Brian E Cade, Hung-Hsin Chen, Yii-Der Ida Chen, Zekai Chen, Paul S De Vries, Latchezar M Dimitrov, Anh Do, Jiawen Du, Charles T Dupont, Todd L Edwards, Michele K Evans, Tariq Faquih, Stephan B Felix, Susan P Fisher-Hoch, James S Floyd, Mariaelisa Graff, Charles Gu, Dongfeng Gu, Kristen G Hairston, Anthony J Hanley, Iris M Heid, Sami Heikkinen, Heather M Highland, Michelle M Hood, Mika Kähönen, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Setoh Kazuya, Tanika N Kelly, Pirjo Komulainen, Daniel Levy, Henry J Lin, Peter Y Liu, Pedro Marques-Vidal, Joseph B Mccormick, Hao Mei, James B Meigs, Cristina Menni, Kisung Nam, Ilja M Nolte, Natasha L Pacheco, Lauren E Petty, Hannah G Polikowsky, Michael A Province, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Stephen S Rich, Renata L Riha, Lorenz Risch, Martin Risch, Edward A Ruiz-Narvaez, Rodney J Scott, Colleen M Sitlani, Jennifer A Smith, Tamar Sofer, Maris Teder-Laving, Uwe Völker, Peter Vollenweider, Guanchao Wang, Ko Willems Van Dijk, Otis D Wilson, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Xiaofeng Zhu, Jennifer E Below, Carsten A Böger, David Conen, Simon R Cox, Marcus Dörr, Mary F Feitosa, Ervin R Fox, Nora Franceschini, Sina A Gharib, Vilmundur Gudnason, Sioban D Harlow, Jiang He, Elizabeth G Holliday, Zoltan Kutalik, Timo A Lakka, Deborah A Lawlor, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Reedik Mägi, Fumihiko Matsuda, Alanna C Morrison, Brenda Wjh Penninx, Patricia A Peyser, Jerome I Rotter, Harold Snieder, Tim D Spector, Lynne E Wagenknecht, Nicholas J Wareham, Alan B Zonderman, Kari E North, Myriam Fornage, Million Veteran Program, Adriana M Hung, Alisa K Manning, James Gauderman, Han Chen, Patricia B Munroe, Dabeeru C Rao, Diana Van Heemst, Susan Redline, Raymond Noordam, Heming Wang

Faculty, Staff and Student Publications

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health …

Chance Or Strategy? Assessing The Unanticipated Policy Window For Active Transportation During The Covid-19 Pandemic: A Systematic Review, Katja Siefken, Michael Pratt, Juliana Mejía-Grueso, Adrian Bauman, Deborah Salvo, Catherine B Woods, Wanda Wendel-Vos, Justin Richards, J Jaime Miranda, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Physical activity (PA) policy is essential for promoting population-level PA by coordinating efforts across various sectors. Global crises like the COVID-19 pandemic can open policy windows, enabling rapid implementation of innovative policies. This study examined how policy windows shaped active transportation (AT) policies during the pandemic, resulting in infrastructural changes.

Methods: A systematic review using PubMed, Scopus, ProQuest-Coronavirus Research Database, Web of Science, WHO COVID-19 Research Database, PsycInfo, and SPORTDiscus conducted to characterize AT policy during the pandemic (2020-2023). Descriptive analyses were conducted in Stata. PROSPERO registration number: CRD42025644930.

Results: The search retrieved 3879 articles; 1162 were duplicates, leaving 2716 …

Accelerometer-Measured Chronoactivity And Type 2 Diabetes Risk: A Prospective Study In Uk Biobank Participants, Qiuyu Feng, Gali Albalak, Ko Willems Van Dijk, Jeroen H P M Van Der Velde, Qian Xiao, Raymond Noordam, Diana Van Heemst

Faculty, Staff and Student Publications

Objective: We assessed whether timing of physical activity, independent from the total activity amount, - which we refer to as chronoactivity - is associated with type 2 diabetes (T2D) risk.

Methods: We included UK Biobank participants with valid accelerometry data (UK, exposure measurement: 2013-2015, follow-up till November 2023) and without diabetes mellitus at baseline (N = 89,439; mean age: 61.7 [SD:7.9] years). Relative hourly physical activity was calculated by dividing the average hourly clock time physical activity by the average hourly physical activity in a week. Participants were categorized into different chronoactivity clusters using k-means cluster analysis on relative hourly …

Evaluating The Antimicrobial Properties Of Different Dental Cleaning Tablets Against S Aureus Grown On Two Denture Base Materials, Sindi Vishaj, Alissa Villhauer, Mandi Morris, Donald M Belles, Daher Antonio Queiroz, Maria D Gonzalez, Ransome Van Der Hoeven

Faculty, Staff and Student Publications

Objectives: This study aimed to evaluate the antimicrobial efficacy of three commercially available denture cleaning tablets Efferdent, Polident, and Val-clean against Staphylococcus aureus biofilms formed on two denture base materials: milled polymethyl methacrylate (PMMA) and 3D printed denture resin.

Material and methods: Eighty samples were fabricated, with 40 specimens per denture base material: CAD/CAM milled PMMA (Lucitone Digital Fit LT; Dentsply Sirona, Charlotte, NC, USA) and 3D printed resin (Denture Base Resin; Formlabs Inc., Somerville, MA, USA). Each group was divided into four subgroups (n = 10), Efferdent, Polident, Val-clean, and deionized water (control). Surface roughness was measured using a …

Genome-Wide Approaches To Bacterial Strain Typing: A History And Review Of Recent Methodological Advances, William C Shropshire, Blake M Hanson, Samuel A Shelburne

Faculty, Staff and Student Publications

Purpose of review: Whole genome sequencing (WGS) has transformed bacterial strain typing, an essential tool for outbreak detection, antimicrobial resistance surveillance, and tracking clonal emergence across clinical, research, and public health settings. Herein, we will review recent advances in WGS-based bacterial strain typing methods for purposes of comparison and classification with a focus on improvements in variant identification, strain classification, and transmission assessment.

Recent findings: Advances in sequencing technologies as well as variant calling methodologies and parameter optimization have enhanced the precision and accuracy of single nucleotide variant identification. Hierarchical clustering of gene-by-gene strain typing, combined with novel data management …

Pain Acceptance In Chronic Postoperative Pain: Concept Analysis, Sajini M Thekkel, Constance M Johnson, Meagan Whisenant, Deniz Dishman

Faculty, Staff and Student Publications

Purpose: Chronic postoperative pain (CPOP) is a potential outcome of otherwise successful surgery that can persist for months, with its prevalence varied by surgical type, genetic predispositions, and psychosocial factors. Pain acceptance offers better outcomes to these patient populations by fostering a willingness to experience pain without resistance. This analysis examines how pain acceptance contributes to psychological well-being, helps reduce opioid misuse, and enhances quality of life, even in the presence of CPOP.

Design: The concept analysis approach follows Walker and Avant's framework (2019).

Methods: A literature search across PubMed, Web of Science, and CINAHL yielded 276 articles, of which …

Effectiveness And Safety Of Chronic Diuretic Use In Older Adults: An Umbrella Review Of Recently Published Systematic Reviews And Meta-Analyses Of Randomized-Controlled Trials, Eveline Van Poelgeest, Konstantinos Prokopidis, Tuğba Erdogan, Min Ji Kwak, Karolina Piotrowicz, Luca Paoletti, Annette Eidam, Fatma Özge Kayhan Koçak, Birkan Ilhan, Alessia Beccacece, George Soulis, Serdar Özkök, Gulistan Bahat, Eva Topinková, Joost Daams, M Louis Handoko, Parag Goyal, Jerzy Gąsowski, Antonio Cherubini, Nicola Veronese, Giuseppe Dario Testa, Wade Thompson, Nathalie Van Der Velde, European Geriatric Medicine Society Special Interest Groups Of I. Pharmacology; Ii. Cardiovascular Disease And Iii. Systematic Review And Meta-Analysis

Faculty, Staff and Student Publications

Background: Healthcare providers should balance the potential risks and benefits of chronic diuretic use, particularly in older adults, as with age, diuretic benefits may decline and risks increase. A comprehensive synthesis and critical evaluation of the available evidence on chronic diuretic treatment effects is currently lacking.

Methods: We conducted an umbrella review of systematic reviews and meta-analyses published since 2018 on health outcomes associated with diuretic use in randomized-controlled trials (RCTs). We conducted random-effects meta-analysis for pooled effect estimates and narratively summarized data that could not be pooled.

Results: We included 741 effect estimations from 117 systematic reviews (SRs) on …

A Systematic Clinical Framework For Postimplantation Monitoring In Thalamic Neuromodulation: Insights From Twiddler's Syndrome, Shalin Shah, Ganne Chaitanya, Jeston Chin, Nicholas Delcimmuto, Jay R Gavvala

Faculty, Staff and Student Publications

This case described a 25-year-old pregnant woman with refractory multifocal epilepsy, diagnosed in 2020 and treated with bilateral thalamic deep brain stimulation (DBS) targeting the centromedian and pulvinar nuclei. Prior to DBS, she experienced daily focal seizures, often progressing to generalized tonic-clonic seizures despite optimal medication. Presurgical evaluations revealed multifocal epilepsy with right hemispheric involvement and diffuse band heterotopia. Given the extensive neurophysiological and radiographic findings, DBS was chosen over resective surgery. Following implantation in December 2023, initial stimulation settings resulted in some seizure control but also development of new symptoms, including shock-like sensations down her neck. After 43 seizure-free …

Does Midbrain Atrophy Distinguish Progressive Supranuclear Palsy From Frontotemporal Dementia?, Mauro César Quintão E Silva Cunningham, Sarah Teixeira Camargos, Vinícius Ribeiro Jeunon, Natalia Pessoa Rocha, Antônio Lúcio Teixeira, Thiago De Oliveira Maciel, Elisa De Paula França Resende, Francisco Eduardo Costa Cardoso, Paulo Caramelli, Leonardo Cruz De Souza

Faculty, Staff and Student Publications

Background: The diagnostic value of midbrain atrophy for distinguishing behavioral variant frontotemporal dementia (bvFTD) from progressive supranuclear palsy (PSP) is unclear.

Objective: To investigate whether measures of midbrain atrophy differentiate PSP from bvFTD.

Methods: We included four groups: healthy controls (n = 19), PSP-Richardson syndrome (n = 20), bvFTD (n = 19) and Parkinson's disease (PD; n = 12). The following quantitative and qualitative measures were calculated: Hummingbird sign rating scale [HBS-RS], global midbrain atrophy [GMA], midbrain area, midbrain/pons ratio, the Magnetic Resonance Parkinsonism Index (MRPI), the MRPI 2.0 and brainstem volume.

Results: Compared to controls, PSP and bvFTD had …

Sex Differences In Etiologies, Risk Factors, And Outcomes Among Young Adult Patients With Acute Ischemic Stroke, Ekta G Shah, Manish Bhojwani, Kelly Chang, Deepa Dongarwar, Nicole R Gonzales, Erica Jones, Audrey Sarah Cohen, Anjail Z Sharrief

Faculty, Staff and Student Publications

Background: The incidence of ischemic stroke is increasing among young adults. Several studies have demonstrated sex differences in risk and outcomes; however, findings are inconsistent. We sought to evaluate sex differences in stroke risk factors, etiology, and disposition in a diverse cohort of patients admitted to a comprehensive stroke center for evaluation.

Methods: We conducted a retrospective study of patients 18-45 years admitted between January 1, 2015 and September 30, 2021 with an acute ischemic stroke. Patient demographics, risk factors, and disposition were extracted from our institutional inpatient stroke registry and inpatient electronic medical record. Stroke etiology was assigned based …

Poor Correlation Between Inflammatory And Brain Injury Biomarkers After Neonatal Intraventricular Hemorrhage: A Pilot Study, Ankit Agarwal, Miriam Zamorano, Aidan Collier, Braden Oldham, Kaleigh Riggs-Harpur, Thao L Nguyen, David I Sandberg, Stephen A Fletcher, Manish N Shah, Brandon A Miller

Faculty, Staff and Student Publications

Background: This study investigated changes in hemoglobin and neuroinflammatory and brain injury biomarkers (tumor necrosis factor-alpha [TNF-α] and glial fibrillary acidic protein [GFAP]) in early stages of cerebrospinal fluid (CSF) diversion in preterm neonates with intraventricular hemorrhage (IVH). We hypothesized that patients with higher CSF hemoglobin levels would have higher TNF-α and GFAP levels.

Methods: This prospective study included infants with grade 3 or 4 IVH. All had ventricular reservoirs that were placed following standard neurosurgical care. The first CSF sample was collected on the day of reservoir placement. Subsequent samples were from clinically indicated CSF withdraws to decompress ventricles. …

Traumatic Brain Injury And Risk Of Malignant Brain Tumors In Civilian Populations, Sandro Marini, Amr R Alwakeal, Hunter Mills, Joshua D Bernstock, Ahmad Mashlah, Muhammad T Hassan, Jakob Gerstl, Farid Radmanesh, Gundolf Schenk, Sharat Israni, Rachel Grashow, E Antonio Chiocca, Cathra Halabi, Anthony Digiorgio, Stephen T Magill, Geoffrey T Manley, Saef Izzy, Ross Zafonte

Faculty, Staff and Student Publications

Importance: A 2024 US study reported that veterans of the Iraq and Afghanistan wars affected by traumatic brain injury (TBI) had an increased risk of developing brain tumors. However, studies among civilians have shown conflicting results and have not replicated the association between TBI and brain tumor risk.

Objective: To examine whether history of TBI in US adult civilians is associated with a risk of subsequent development of malignant brain tumors.

Design, setting, and participants: This retrospective cohort study used data from a tertiary academic medical center (Mass General Brigham [MGB]) patient data registry encompassing January 1, 2000, to January …

The Effect Of Maternal Antioxidant Vitamin Supplementation On Maternal And Cord Blood Adiponectin Concentrations, Jessica L Pippen, Paula Mcgee, James M Roberts, Leslie Myatt, Michael W Varner, Alan T N Tita, Ronald J Wapner, John M Thorp, Brian M Mercer, Beth A Plunkett, Sean C Blackwell, Anthony Sciscione, George R Saade

Faculty, Staff and Student Publications

Adiponectin is a hormone that modulates glucose regulation and fatty acid oxidation. Low adiponectin concentration has been associated with increased insulin resistance. Studies show a beneficial effect of vitamin E supplementation on insulin sensitivity. We aimed to investigate the association of prenatal antioxidant supplementation with increased adiponectin concentrations in pregnant participants and their newborn infants.Secondary analysis of a randomized control trial of prenatal vitamin C and E supplementation to prevent preeclampsia in low-risk nulliparous participants. Plasma of participants at time of randomization (9-16 weeks gestation) and delivery, and neonatal cord blood were analyzed by specific enzyme-linked immunosorbent assay for adiponectin …

Isolation And Functional Properties Of Highly-Purified N-Terminal Domain Of Human Napi2b By Scalable “Resin Overload” Technique, Daria Savenkova, Irina Makarenko, Daria Nedorezova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Despite the enthusiasm and advances in the purification of native and engineered full-length membrane proteins, little attention has been paid to their fragments which could serve as attractive inspiration for function, regulation, or targeting of full-length membrane protein with therapeutic antibodies (Abs). Production of recombinant fragments of "therapeutic" membrane proteins for early-stage discovery research requires their purification to near homogeneity. It is important not only for the production of biotherapeutic antibodies but also for structural and functional studies of competitive protein-Abs, protein-protein, and lipid-protein interactions which heavily rely on the purity and quality of the isolated protein fragment of interest. …

2025 European Leukemianet Recommendations For The Management Of Chronic Myeloid Leukemia, Jane F Apperley, Dragana Milojkovic, Nicholas C P Cross, Henrik Hjorth-Hansen, Andreas Hochhaus, Hagop Kantarjian, Jeffrey H Lipton, Hemant Malhotra, Dietger Niederwieser, Jerald Radich, Philippe Rousselot, Susanne Saussele, Charles A Schiffer, Richard Silver, Simona Soverini, Leif Stenke, Anna Turkina, Luis Felipe Casado, Fausto Castagnetti, Francisco Cervantes, Richard E Clark, Jorge Cortes, Michael Deininger, Timothy P Hughes, Jeroen Janssen, Qian Jiang, Dong-Wook Kim, Richard A Larson, Francois X Mahon, Michael Mauro, Jiri Mayer, Franck E Nicolini, Fabrizio Pane, Delphine Rea, Johan Richter, Gianantonio Rosti, Giuseppe Saglio, Rüdiger Hehlmann

Faculty, Staff and Student Publications

In this 5th version of the European LeukemiaNet guidance for adult patients, there are important changes in several areas of management based on evidence available since 2020, including the World Health Organisation's reclassification of CML as a biphasic disease. Previous advice to switch the tyrosine kinase inhibitor (TKI) on failure of molecular milestones, is modified to better account for individual patient circumstances. Our recommendations are summarized in tables designed to be read in conjunction with the text which offers justification and additional advice. We describe decision-making for first-line treatment, both in available drugs and their initial dosing. Similarly we elaborate …

Addressing Challenges In Developing Treatments For Inherited Retinal Diseases: Recommendations From The Third Monaciano Symposium, Debra A Thompson, K Thiran Jayasundera, Oleg Alekseev, Robin R Ali, Alessia Amato, Vadim Y Arshavsky, Isabelle S Audo, Alberto Auricchio, James W B Bainbridge, Eyal Banin, Cagri G Besirli, David G Birch, Kari E Branham, Artur V Cideciyan, Stephen P Daiger, Jacque L Duncan, Abigail T Fahim, John G Flannery, Roberto Gattegna, John R Heckenlively, Elise Héon, Alessandro Iannaccone, Naheed W Khan, Samer Khateb, Henry J Klassen, Bart P Leroy, Dario Marangoni, Michel Michaelides, David C Musch, Mark E Pennesi, Simon M Petersen-Jones, Eric A Pierce, Rajesh C Rao, José-Alain Sahel, Paul A Sieving, Enrica Strettoi, Cameron R Strong, Thomas J Wubben, Paul Yang, David N Zacks

Faculty, Staff and Student Publications

Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to provide safe and effective therapies for these rare conditions. Although several ongoing programs remain poised for success, numerous challenges have negatively impacted the ability to obtain regulatory approvals. The present position paper briefly summarizes recent advances and challenges in developing therapeutics for inherited retinal diseases, and presents a set of recommendations for moving the field forward. The priorities identified are discussed in terms of progress …

Transcriptomic Analysis Of Localized High-Risk Prostate Cancer Improves Prognostication And Identifies Benefit From Adding Docetaxel To Definitive Radiotherapy With Androgen Suppression In The Nrg Oncology/Rtog 0521 Phase 3 Trial, Ryan M Phillips, James A Proudfoot, Elai Davicioni, Yang Liu, Daniel E Spratt, Jeff M Simko, Robert B Den, Alan Pollack, Seth A Rosenthal, A Oliver Sartor, Christopher J Sweeney, Gerhardt Attard, Leslie Longoria, Samir Patel, Michael W Straza, Jason A Efstathiou, Amit B Shah, Karen E Hoffman, Joseph P Rodgers, Howard M Sandler, Felix Y Feng, Phuoc T Tran

Faculty, Staff and Student Publications

Background and objective: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.

Methods: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Sinus Tarsi Versus Extended Lateral Approach For Displaced Intra-Articular Calcaneal Fractures: A Single Surgeon's Experience, Philip K Lim, Adam J Miller, Justin Haghverdian, Ramzy Meremikwu, M Kareem Shaath, John W Munz

Faculty, Staff and Student Publications

Background

The aim of the study is to investigate the differences between the extensile lateral (EL) and sinus tarsi (ST) approaches for the treatment of displaced intra-articular calcaneus fractures as treated by a single surgeon.

Methods

A retrospective cohort study performed at a Level 1 trauma center. One hundred twenty-nine consecutive intra-articular calcaneus fractures from 2011 to 2018 that were surgically treated by a single surgeon. Primary outcomes were time to surgery, operative time, postoperative restoration of the critical angle of Gissane, postoperative wound complications, and need for unplanned re-operation.

Results

Patient characteristics, including demographics, mechanism of injury, and fracture …

Telepathology In Hematopathology Diagnostics: A Collaboration Between The Ho Chi Minh City Oncology Hospital And The University Of Texas Health-Mcgovern Medical School, Uyen Ly, Quang Nguyen, Dang Nguyen, Tu Thai, Binh Le, Duong Gion, Alexander Banerjee, Brenda Mai, Amer Wahed, Andy Nguyen

Faculty, Staff and Student Publications

Digital pathology in the form of whole-slide imaging has been used to support diagnostic consultation through telepathology. Previous studies have mostly addressed the technical aspects of telepathology and general pathology consultation. In this study, we focus on our experience at the University of Texas Health-McGovern Medical School in Houston, Texas, in providing hematopathology consultation to the Pathology Department at the Ho Chi Minh City Oncology Hospital in Vietnam. Over a 32-month period, 71 hematopathology cases were submitted for telepathology. Consensus was reached for a definitive diagnosis in 97% of all cases. Diagnostic efficiency significantly improved with average turnaround times reduced …

Bayesian Counterfactual Machine Learning Individualizes Radiation Modality Selection To Mitigate Immunosuppression, Duo Yu, Michael J Kane, Yiqing Chen, Steven H Lin, Radhe Mohan, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.

Methods: A novel Bayesian causal inferential technique is introduced and applied to a matched retrospective cohort of 510 patients with esophageal cancer undergoing CRT to identify patient profiles …

Celebrating The Fifth Edition Of The International Symposium On Fungal Stress – Isfus, A Decade After Its 2014 Debut, Alene Alder-Rangel, Amanda E A Rangel, Arturo Casadevall, Asiya Gusa, Chaoyang Xue, Charles M Boone, Chris Todd Hittinger, Claudio A Masuda, Consuelo Olivares-Yañez, Deborah Bell-Pedersen, Erica J Washington, Gerhard Braus, Guilhem Janbon, István Pócsi, Jason E Stajich, Jay C Dunlap, Joan W Bennett, Joseph Heitman, Ling Lu, Lucia Landi, Mari L Shinohara, Maurizio Del Poeta, Mavis A Acheampong, Mia R Maltz, Michael C Lorenz, Minou Nowrousian, N Louise Glass, Nichole A Broderick, Nicolás Pedrini, Nir Osherov, R Blake Billmyre, Sabrina Sarrocco, Salomé Leibundgut-Landmann, Vânia Aparecida Vicente, Xiaorong Lin, Xin-Qing Zhao, Yong-Sun Bahn, Zachary A Lewis, Drauzio E N Rangel

Faculty, Staff and Student Publications

The Fifth International Symposium on Fungal Stress (ISFUS) brought together in Brazil many of the leaders in the field of fungal stress responses, from fourteen countries, for four days of outstanding science ranging from basic research to studies with agricultural, medical, industrial, and environmental significance. In addition to the excellent oral and poster presentations, the Symposium organisers ensured that all participants had ample opportunity to engage, socialise, and network to exchange ideas and share research. The conference was enhanced by the world-class venue near Iguazu Falls, probably the greatest natural phenomenon in South America.

Development Of A Multi-Institutional Dataset To Validate A Novel Inflammatory Breast Cancer Diagnostic Score, Filipa Lynce, Samuel M Niman, Megumi Kai, Sean Ryan, Elizabeth Troll, Li Li, Kathy D Miller, Reshma Jagsi, Ginny Mason, Beth A Overmoyer, H T Carisa Le-Petross, Faina Nakhlis, Savitri Krishnamurthy, Beth T Harrison, Susie X Sun, Eren D Yeh, Jennifer R Bellon, Laura E Warren, Michael C Stauder, Meredith M Regan, Wendy A Woodward

Faculty, Staff and Student Publications

Background: Susan G. Komen, the Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to propose novel quantitative scoring rubrics for IBC diagnosis. In this study, we developed a multi-institutional clinical dataset to test and validate the proposed scoring system.

Methods: IBC (N = 988) and non-IBC (N = 332) cases were identified at 2 institutions with dedicated multidisciplinary IBC programs. The non-IBC cohort included consecutive cT4b and cT4c patients. Standard operating procedures (SOPs) were developed for all ambiguous findings and languages. Three different methods were used for the imputation of missing data, …

Human And Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition And Microglia-Dependent Plaque Response In Aged Mice, Juana Andreo-Lopez, Cristina Nuñez-Diaz, Kelly Do Huynh, Marie Minh Thu Nguyen, Celia Da Cunha, Francisco J Cantero-Molina, Cynthia Campos-Moreno, Stefania Zimbone, Francesco Bellia, Maria Laura Giuffrida, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Miriam Bettinetti-Luque, Nazaret Gamez, Catalina Valdes, Rodrigo Morales, Stefania Forner, Alessandra C Martini, Antonia Gutierrez, Frank M Laferla, David Baglietto-Vargas

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or "seeding" process. These Aβ and tau "seeds" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we employed histological and molecular approaches to determine whether seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates …

A Comparative Study Of Recent Large Language Models On Generating Hospital Discharge Summaries For Lung Cancer Patients, Yiming Li, Fang Li, Na Hong, Manqi Li, Kirk Roberts, Licong Cui, Cui Tao, Hua Xu

Faculty, Staff and Student Publications

Objective: Generating discharge summaries is a crucial yet time-consuming task in clinical practice, essential for conveying pertinent patient information and facilitating continuity of care. Recent advancements in large language models (LLMs) have significantly enhanced their capability in understanding and summarizing complex medical texts. This research aims to explore how LLMs can alleviate the burden of manual summarization, streamline workflow efficiencies, and support informed decision-making in healthcare settings.

Materials and methods: Clinical notes from a cohort of 1,099 lung cancer patients were utilized, with a subset of 50 patients for testing purposes, and 102 patients used for model fine-tuning. This study …

Inhibition Of Methylthioadenosine Phosphorylase Protects From Experimental Acute Kidney Injury, Afaf Saliba, Yidong Chen, Jonathan W Nelson, Abhinav Vetcha, Wei Wei Wang, Li Kang, Nagarjunachary Ragi, Soumya Maity, Hamid Rabb, W Brian Reeves, Kumar Sharma

Faculty, Staff and Student Publications

Methylthioadenosine phosphorylase (MTAP) is a key enzyme in purine metabolism that may influence cellular responses to injury. We evaluated the effects of prophylactic MTAP inhibition in mouse models of ischemia-reperfusion and cisplatin-induced acute kidney injury (AKI). MTAP inhibition was confirmed by accumulation of methylthioadenosine (MTA). Treated mice showed reduced renal injury and decreased tubular damage. Transcriptomic analysis revealed protection from inflammatory and stress pathways, while maintaining oxidative phosphorylation, fatty acid metabolism, and epithelial integrity-related genes. Analysis of human single-cell RNA-seq data from the Kidney Precision Medicine Project indicated that MTAP is highly expressed in kidney injury marker-positive adaptive proximal tubule …

Associative Coding Of Conditioned Fear In The Thalamic Nucleus Reuniens In Rodents And Humans, Tuğçe Tuna, Michael S Totty, Muhammad Badarnee, Flávio Afonso Gonçalves Mourão, Shaun Peters, Mohammad R Milad, Stephen Maren

Faculty, Staff and Student Publications

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remain unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. …