Digital Commons Network^™

Rna Interference In Protozoan Parasites And Its Application, Lon-Fye Lye, Deborah E Dobson, Stephen M Beverley, Min-Che Tung

2020-Current year OA Pubs

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression, via small RNA triggers derived from double-stranded RNA that can target specific genes; it is a natural process that plays a role in both the regulation of protein synthesis and in immunity. Discovery of RNAi by Fire and Mello in 1998 had a profound impact on unraveling novel aspects of eukaryotic biology. RNA interference (RNAi) has proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms. A great advance in …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Hiroko Yano, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

METHODS: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

RESULTS: NF2 loss-of-function (LOF) …

Age-Related Mesenchymal Stromal Cell Senescence Is Associated With Progression From Mgus To Multiple Myeloma, Natalya Plakhova, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) increases with advancing age, suggesting that progression may be influenced by age-related changes within the bone marrow (BM) microenvironment. We hypothesise that senescent mesenchymal stromal cells (MSCs), which accumulate in the BM with age, may contribute to MGUS progression to MM. Here, we show that, like BM MSCs from aged non-cancer controls, BM MSCs from both MM and MGUS patients exhibit a senescent phenotype characterised by enlarged, flattened morphology, increased β-galactosidase activity and CDKN2A expression, and decreased proliferation rate compared with BM MSCs from healthy …

White Matter Microstructure In School-Age Children With Down Syndrome, Dea Garic, Robert C Mckinstry, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution …

Measuring And Interpreting Individual Differences In Fetal, Infant, And Toddler Neurodevelopment, Halie A Olson, M Catalina Camacho, Natasha Marrus, Et Al.

2020-Current year OA Pubs

As scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a "standard" way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying "development" influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research …

A Systematic Review And Meta-Analysis Of Social Cognition Among People Living With Hiv: Implications For Non-Social Cognition And Social Everyday Functioning, David E Vance, Rebecca Billings, Crystal Chapman Lambert, Pariya L Fazeli, Burel R Goodin, Mirjam-Colette Kempf, Leah H Rubin, Bulent Turan, Jenni Wise, Gerhard Hellemann, Junghee Lee

2020-Current year OA Pubs

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Plasma Mtbr-Tau243 Biomarker Identifies Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Rama K Koppisetti, Nicolas R Barthélemy, Yingxin He, Chihiro Sato, Brian A Gordon, Hong Jiang, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma …

A Subset Of Cortical Areas Exhibit Adult-Like Functional Network Patterns In Early Childhood, Jiaxin Cindy Tu, Xintian Wang, Donna Dierker, Chloe M. Sobolewski, Evan M Gordon, Timothy O Laumann, Adam T Eggebrecht, Muriah D. Wheelock, Et Al.

2020-Current year OA Pubs

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized into functional networks. These networks show stronger internal and weaker external functional connectivity (FC), with FC profiles more similar within the same network. Previous studies have shown these networks develop from nascent forms before birth to their mature, adult-like structures in childhood. However, these analyses often rely on adult functional network definitions. This study assesses the potential misidentification of infant functional networks when using adult models and explores the consequences and possible solutions to this problem. Our findings suggest that although adult …

Best Practices For A Competency-Based Curriculum In Critical Care Ultrasonography For Fellows, Paru Patrawalla, Frances West, Navitha Ramesh, Paul Mayo, Amik Sodhi

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

New guidelines from the Accreditation Council on Graduate Medical Education for critical care ultrasound (CCUS) training went into effect on July 1, 2024, for critical care medicine and combined pulmonary and critical care medicine fellows. Fellowship programs will need to ensure that their fellows demonstrate competence in skills that are essential to CCUS, which currently encompasses applications in basic cardiac, lung/pleural, abdominal, and vascular ultrasonography (US). This may be a challenge for fellowship programs that have nascent CCUS curricula and limited faculty expertise. In this Perspective, we share expert and evidence-based recommendations on how to implement a competency-based curriculum in …

Long-Term Non-Conditional And Conditional Metastasis Of Uveal Melanoma By Tumor Size Category In 8034 Patients, Rolika Bansal, Hidayet Sener, Jerry A. Shields, Carol L. Shields

Wills Eye Hospital Papers

PURPOSE: To estimate metastasis of patients with uveal melanoma (UM) based on tumor size categories classified by ultrasonographic thickness as small (0.0-3.0 mm), medium (3.1-8.0 mm), or large (≥8.1 mm) using both non-conditional and conditional analyses.

DESIGN: Retrospective analysis.

METHODS: A retrospective study of 8034 cases over 35-years at a single ocular oncology referral center evaluated the primary endpoint of cumulative incidence of metastasis at 5-, 10-, 15-, 20-, 25- and 30-years using non-conditional and conditional analysis at 3-years, 5-years, and 10-years of metastasis-free survival.

RESULTS: The mean thicknesses for small, medium, and large UMs were 2.5 mm, 5.0 mm, …

Cervical, Breast, And Colorectal Cancer Screening Outcomes Among Refugees In Philadelphia, Pennsylvania, Colleen Payton, Nina Kvaratskhelia, Melanie Chalfin, Jessica Deffler, Marc Altshuler

Department of Family & Community Medicine Faculty Papers

Cancer screening can detect cancer at an early stage and decrease cancer morbidity and mortality. Refugee populations may have had limited access to cancer screening before arrival in the United States. A cross-sectional analysis of cervical, breast, and colorectal cancer screening was conducted among refugees with primary care visits between 2018 and 2022 at a refugee health clinic in Philadelphia, Pennsylvania. Cancer screening outcomes included the number and type of screenings; the number of normal, inconclusive, and abnormal screening results; completion of follow-up tests for inconclusive and abnormal results; and the number of cancer diagnoses. Among 149 refugee women aged …

Diabetes-Related Distress Over Time And Its Associations With Glucose Levels In School-Aged Children., Susana R. Patton, Nicole Kahhan, Amy Milkes, Ryan J. Mcdonough, Matthew Benson, Mark A. Clements, Jessica S. Pierce

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: In a cohort of families of school-age children (8-12.99 years old) with type 1 diabetes, we examined the stability of parent and child diabetes-related distress (DRD) over 6 months and the associations between parent and child DRD and child glycated hemoglobin (HbA1c) over time.

RESEARCH DESIGN AND METHODS: We recruited families from two large pediatric hospital systems in the USA and used validated measures of parent (Parent Problem Areas in Diabetes-Child, PPAID-C) and child (Problem Areas in Diabetes-Child, PAID-C) DRD and children's HbA1c. We collected data at baseline and 6 months. We calculated minimal clinically important differences in PPAID-C …

Evolution Of The Family Medicine Clerkship: A Cera Secondary Analysis., Bryce A Ringwald, David Banas, Allison Macerollo, Ericka Bruce, Matthew Farrell

Medical Education Articles

BACKGROUND AND OBJECTIVES: The family medicine clerkship has been found to influence medical students' decision-making regarding specialty choice. Understanding how the family medicine clerkship has changed over the past decade may assist in recruitment efforts. Our study explored trends in family medicine clerkship design, length, and format and correlated these characteristics with high proportions of medical school graduates choosing family medicine.

METHODS: We performed a secondary analysis of the Council of Academic Family Medicine Educational Research Alliance annual family medicine clerkship director surveys from 2012 to 2023. We analyzed standard family medicine clerkship structure questions that were asked in each …

Large-Scale Plasma Proteomic Profiling Unveils Diagnostic Biomarkers And Pathways For Alzheimer’S Disease, Gyujin Heo, Ying Xu, Erming Wang, Muhammad Ali, Hamilton Se-Hwee Oh, Patricia Moran-Losada, Federica Anastasi, Armand González Escalante, Raquel Puerta, Soomin Song, Jigyasha Timsina, Menghan Liu, Daniel Western, Katherine Gong, Yike Chen, Pat Kohlfeld, Allison Flynn, Alvin G Thomas, Joseph Lowery, John C Morris, David M Holtzman, Joel S Perlmutter, Suzanne E Schindler, Natalia Vilor-Tejedor, Marc Suárez-Calvet, Pablo García-González, Marta Marquié, Maria Victoria Fernández, Mercè Boada, Amanda Cano, Agustín Ruiz, Bin Zhang, David A Bennett, Tammie Benzinger, Tony Wyss-Coray, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga

Faculty, Staff and Student Publications

Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer's disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to identify new proteins, pathways and predictive models for AD. We identified 416 proteins (294 new) associated with clinical AD status and validated the findings in two external datasets representing more than 7,000 samples. AD-related proteins reflected blood-brain barrier disruption and other processes implicated in AD, such as lipid dysregulation or immune responses. A machine learning model was used to identify a set …

Allergic Fungal Rhinosinusitis Diagnosis, Management, Associated Conditions, Pathophysiology, And Future Directions: Summary Of A Multidisciplinary Workshop, Lauren T Roland, Cecelia Damask, Amber U Luong, Antoine Azar, Charles S Ebert, Thomas Edwards, Katherine N Cahill, Do-Yeon Cho, David Corry, Tara L Croston, Alexandra F Freeman, Amin Javer, Paneez Khoury, Jean Kim, Michael Koval, Edward D Mccoul, James W Mims, Anju Peters, Jay F Piccirillo, Richard P Ramonell, Amali Samarasinghe, Robert P Schleimer, Prestina Smith-Davidson, Andrej Spec, Michael E Wechsler, Sarah K Wise, Joshua M Levy

The Brown Foundation: Institute of Molecular Medicine

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research …

Identification And Functional Assessment Of Candidate Causal Cis-Regulatory Variants Underlying Electrocardiographic Qt Interval Gwas Loci, Supraja Kadagandla, Lavanya Gunamalai, Dongwon Lee, Ashish Kapoor

The Brown Foundation: Institute of Molecular Medicine

Background: Identifying causal variants among tens or hundreds of associated variants at each locus in genome-wide association studies is challenging. As the vast majority of genome-wide association studies variants are noncoding, sequence variation at cis-regulatory elements (CREs) affecting transcriptional expression of specific genes is a widely accepted molecular hypothesis. Following this hypothesis, combined with the observation that open chromatin is a universal hallmark of all types of CREs, we aimed to identify candidate causal cis-regulatory variants underlying QT interval genome-wide association studies loci.

Methods: Common variants in high linkage disequilibrium with genome-wide significant variants were identified using variant …

Monte Carlo Study Of Gold Nanoparticle-Mediated Radiosensitization Effects Using Nanoscale Cell Model Combined With Fractal-Based Dna Model, Amrit Kaphle, Sandun Jayarathna, Sunil Krishnan, Sang Hyun Cho

The Brown Foundation: Institute of Molecular Medicine

Background: Gold nanoparticles (GNPs) are promising radiosensitizers in radiation therapy, yet the exact mechanisms behind their effectiveness remain not fully understood. Monte Carlo (MC) simulations have been used to study extra energy deposition and increased DNA damage by the secondary electrons from intracellularly present GNPs, which are believed to be the key physical mechanisms responsible for the radiosensitization effects observed in many radiobiological studies. However, discrepancies between experimental results and computational predictions persist. While often attributed to purely biological effects, such discrepancies, from a physical modeling point of view, can also be due to the use of MC models constructed …

Allergic Fungal Rhinosinusitis Diagnosis, Management, Associated Conditions, Pathophysiology, And Future Directions: Summary Of A Multidisciplinary Workshop, Lauren T Roland, Cecelia Damask, Amber U Luong, Antoine Azar, Charles S Ebert, Thomas Edwards, Katherine N Cahill, Do-Yeon Cho, David Corry, Tara L Croston, Alexandra F Freeman, Amin Javer, Paneez Khoury, Jean Kim, Michael Koval, Edward D Mccoul, James W Mims, Anju Peters, Jay F Piccirillo, Richard P Ramonell, Amali Samarasinghe, Robert P Schleimer, Prestina Smith-Davidson, Andrej Spec, Michael E Wechsler, Sarah K Wise, Joshua M Levy

The Brown Foundation: Institute of Molecular Medicine

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research …

The Association Of Vision And Hearing Impairment On Cognitive Function And Loneliness: Evidence From The Mexican Health And Aging Study, Kimberly Hreha, Rafael Samper-Ternent, Heather E Whitson, L P Downer, Jessica S West, Brian Downer

Faculty, Staff and Student Publications

Objectives: We investigated whether self-reported vision and hearing were associated with cognitive function and loneliness among Mexican adults aged 50 and older.

Methods: Mexican Health and Aging Study data. Vision/hearing status was self-reported (excellent-very good, good, fair-poor). Cognition was measured using nine tasks. Loneliness was measured using the UCLA Loneliness Scale. Analyses controlled for demographic and health characteristics.

Results: Among 12,353 participants (mean age = 67, 58% female), poor vision, but not hearing, was associated with lower global cognition (β = -0.03, p < .05). Poor vision (OR = 1.57, 95% CI = 1.30-1.91) and hearing (OR = 1.35, 95% CI = 1.14-1.61) were associated with higher odds of being lonely after adjusting for demographics and comorbidities, but not when adjusting for limitations in daily activities and depressive symptoms.

Discussion: Poor vision is a potentially modifiable risk factor for lower cognition and loneliness among Mexican adults. …

Understanding Utilization And Prevention Measures Associated With A Caries Risk Assessment In Oral Health Transformation, Melody Mcgee, Ryan Brandon, Muhammad Walji, Joel White, Kristen Moses, Eric P Tranby, Lisa J Heaton, Kristen Simmons

Faculty, Staff and Student Publications

Objectives: Dental decay is endemic in the United States, underscoring the need to measure the utilization of caries risk management tools to elucidate the effect of prevention interventions in reducing the dental decay rates of individuals. An academic institution partnered with a third-party institute to call attention to the utilization and prevention measures associated with caries risk assessment (CRA) used with children 0-18 years. This environmental scan examined claims across the United States to evaluate the proportion of dental examinations, CRAs, and caries prevention procedures within a calendar year.

Methods: A 12-month deidentified participant list categorized by age, race, sex, …

Navigating Early Career As An Oncologist: Thriving In Diverse Paths., Gita Suneja, Marjorie C Green, Janaki Parameswaran, Joseph Mccollom Do

PCI Publications and Projects

Early-career oncologists navigate a complex landscape of professional development, clinical responsibilities, and research endeavors. This manuscript explores key challenges and strategies for success in the early years of an oncology career, focusing on the first job after fellowship, career transitions, and practical tips for intentionality. Effective mentorship is pivotal, providing guidance in clinical decision making, research pursuits, and professional networking. Career development strategies include securing funding, building collaborative networks, and identifying opportunities for leadership. Additionally, balancing clinical duties with research and personal well-being requires time management and institutional support. This article emphasizes the importance of fostering inclusive mentorship, advocating for …

The Macrophage Sterol Transport Protein Orp2 Promotes Cholesterol Efflux And Prevents Foam Cell Formation And Atherosclerosis, Xiaowei Wang, Kenan Peng, Yudi Zhao, Liwen Qiu, Chenxi Liang, Yaqian Dou, Qianqian Dong, Xiaoting Ma, Jinye Tang, Yidan Ma, Lin Liu, Mingqi Zheng, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2MOE) mice were generated and crossed with atherosclerotic-prone ApoE−/− mice and then fed a high-fat diet (HFD) to induce atherosclerosis. Our results showed that myeloid-specific hORP2 overexpression significantly reduced the atherosclerotic …

Perceptions Of The Intensity Of Heart Failure Medications Among Hospitalized Older Adults: A Pilot Qualitative Study, Nuzha A Amjad, Saeed Shoar, Catherine Bryant, Meghan Hunt, Min Ji Kwak

Faculty, Staff and Student Publications

Background: Guidelines for heart failure (HF) management recommend high target doses for medications. These targets are based on standardized dosing regimens that rarely consider the complex challenges faced by older patients. However, little is known about such challenges perceived by older adults. We assessed older adults' perceived challenges with HF medication utilization, which may guide a more patient-centered definition of the target intensity for HF medications.

Methods: We conducted a pilot qualitative study using one-on-one, semi-structured interviews with older adults. We included patients over the age of 65 years admitted to the acute cardiac care units (cardiac intensive care unit …

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques, Jumah G Ahmad, Alexander J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

Placenta Accreta Spectrum, Present And Future: The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Workshop Summary, Christina M Duzyj, Brett D Einerson, Yalda Afshar, Karin A Fox, Antonio F Saad, Daniela A Carusi, Christina L Herrera, Deirdre J Lyell, Alfred Z Abuhamad, Michaela K Farber, Anne C Roberts, Sebastian R Hobson, Loic Sentilhes, Baha M Sibai, Koji Matsuo, Kristen Terlizzi, Scott A Shainker, Robert M Silver, Helena C Bartels, Thomas D Shipp, Marilyn Huang, Alison G Cahill, Jason D Wright, George R Saade, Monica Longo

Faculty, Staff and Student Publications

Placenta accreta spectrum (PAS) disorder poses significant risks to maternal health, given the complexities of screening, diagnosis, and management. To address these challenges, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) hosted a workshop on June 10-11, 2024, bringing together expert health care professionals, researchers, stakeholders, and patient advocates to identify knowledge gaps, with an overarching goal of informing future research and best practices for PAS. Key discussions revolved around the resources and infrastructure needed to advance screening, diagnosis, and clinical management of PAS, alongside ways to enhance collaboration across disciplines. Participants considered strategies to …

Prematurity And Congenial Diaphragmatic Hernia: Revisiting Outcomes In A Contemporary Cohort, Petru I Alexe, Ana Sanchez Torres, Ashley H Ebanks, Enrico Danzer, Krisa Van Meurs, Matthew T Harting, Carmen Mesas Burgos

Faculty, Staff and Student Publications

Objective: To describe outcomes in a contemporary cohort of infants born at gestational age < 34 weeks with congenital diaphragmatic hernia (CDH).

Study design: Data from the multicenter, multinational CDH Study Group (CDHSG) registry on patients born between 1995 and 2022 were analyzed. Variables including prenatal characteristics and therapy, postnatal management, and outcomes to discharge were evaluated. A t test was used for continuous variables, and for categorical variables, the Fisher exact test.

Results: In total, 13 471 patients with CDH were entered into the registry during the study period. 810 (6%) were born at < 34 weeks of gestational age. The survival rate for the preterm cohort was 45%, and 43.5% were not repaired. Survival after surgical repair was 79%, mean age at surgery was 11 days of life, and 65% required patch repair. Extracorporeal life support was used in only 7% of the cases, and 35% survived. In total, 48.9% had an associated anomaly. Oxygen at 30 days of life was required by 76.7%. Very preterm birth (< 32 weeks of gestational age) occurred in 361 patients (2.8%), with a 39.3% survival rate and a high rate of nonrepairs (50.1%). The incidence of birth at < 34 weeks of gestational age for those undergoing fetal tracheal occlusion was 30%.

Conclusions: Survival rates for infants born preterm with CDH remain low and the …

One Cutoff Is Not Enough: Assessing Different Area Deprivation Index Cutoffs For Insurance Types On Surgical Desirability Of Outcome Ranking (Door), Susanne Schmidt, Michael A Jacobs, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Background: Social Determinants of Health impact health outcomes. Area Deprivation Index (ADI) is used to risk-adjust for neighborhood affluence/deprivation but guidance on choosing deprivation cutoffs is lacking. We hypothesize that different ADI cutoffs are required for different insurance types.

Methods: National Surgical Quality Improvement Program data 2013-2019 merged with electronic health records from three academic healthcare systems. Desirability of Outcome Ranking (DOOR) assessed the association of ADI cutoffs for different insurance types, adjusted for operative stress, frailty, and case status (elective, urgent, emergent). Secondary analyses assessed the association of ADI with case status.

Results: Patients with Private insurance living in …

Salicylamide Derivative Jmx0312 Protects Immunosuppressed Syrian Hamsters Against Adenovirus Lethal Challenge, Marta Carretero-Ledesma, Jun Li, Javier Martín-Escolano, Soraya Herrera-Espejo, Jimin Xu, Haiying Chen, Caridad Díaz-Navarro, Jerónimo Pachón, Javier Sánchez-Céspedes, Jia Zhou, María Eugenia Pachón-Ibáñez

Faculty, Staff and Student Publications

Despite the fact that human adenovirus (HAdV) causes severe infections in immunosuppressed and immunocompetent individuals, especially in children, there is currently no specific treatment for these infections. Previously we reported a new salicylamide analogue, JMX0312, as a potent inhibitor of HAdV infection with low cytotoxicity in vitro. Here we evaluate the in vivo efficacy and safety of this molecule in the immunosuppressed Syrian hamster model of HAdV infection. JMX0312 administration at a dose of 6.25 mg/kg did not affect the body weight of the animals, and reduced the viral load in liver and blood in a similar way than cidofovir. …

Glutamatergic Regulation Of Mirna-Containing Intraluminal Vesicle Trafficking And Extracellular Vesicle Secretion From Cortical Neurons, Marcela Bertolio, Qiyi Li, Francesca E Mowry, Kathryn E Reynolds, Rashed Alananzeh, Haichao Wei, Kyoeun Keum, Rachel Jarvis, Jiaqian Wu, Yongjie Yang

Faculty, Staff and Student Publications

Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP+ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters …