Medicine and Health Sciences Commons^™

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Cancer And Leukemia Group B-Southwest Oncology Group 80702 (Alliance), Justin C Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M Goldberg, Eileen M O'Reilly, Anthony F Shields, Jeffrey A Meyerhardt

2020-Current year OA Pubs

BACKGROUND: Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown.

METHODS: This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free …

Correlating Clinical Course With Baseline Subcortical Shape In Provisional Tic Disorder, Tiffanie Che, Soyoung Kim, Deanna J Greene, Ashley Heywood, Jimin Ding, Tamara Hershey, Bradley L Schlaggar, Kevin J Black, Lei Wang

2020-Current year OA Pubs

OBJECTIVE: This study examined children at the onset of tic disorder (tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the baseline shape and volume of subcortical nuclei, diagnosis, and tic symptom outcomes.

METHODS: 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder/Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic …

Radiation Oncology Opinions And Practice On Cardiotoxicity In Lung Cancer: A Cross-Sectional Study By The International Cardio-Oncology Society, G M Walls, J D Mitchell, A R Lyon, M Harbinson, G G Hanna

2020-Current year OA Pubs

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice.

MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the …

Development Of A Deep Learning Algorithm For Paneth Cell Density Quantification For Inflammatory Bowel Disease, Liang-I Kang, Kathryn Sarullo, Jon N Marsh, Liang Lu, Pooja Khonde, Changqing Ma, Talin Haritunians, Angela Mujukian, Emebet Mengesha, Dermot P B Mcgovern, Thaddeus S Stappenbeck, S Joshua Swamidass, Ta-Chiang Liu

2020-Current year OA Pubs

BACKGROUND: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation. Our aim was to use DL to quantify PCs for use as a quantitative biomarker.

METHODS: A retrospective cohort of whole slide images (WSI) of ileal tissue samples from patients with/without inflammatory bowel disease (IBD) was used for the study. A pathologist-annotated training set …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Rachel L Henson, Beau Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

METHODS: We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium-Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Genomic Insights For Personalised Care In Lung Cancer And Smoking Cessation: Motivating At-Risk Individuals Toward Evidence-Based Health Practices, Tony Chen, Giang Pham, Louis Fox, Alex T Ramsey, Laura J Bierut, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes.

METHODS: We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardised PRS distributions across all ancestries. We validated our PRSs in 561,776 individuals of diverse ancestry …

Disentangling The Unique Contributions Of Age, Pubertal Stage, And Pubertal Hormones To Brain Structure In Childhood And Adolescence, Mark Curtis, John C Flournoy, Sridhar Kandala, Ashley F P Sanders, Michael P Harms, Adam Omary, Leah H Somerville, Deanna M Barch

2020-Current year OA Pubs

Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks. Sex and age explain the most unique variance in all three aspects of structural development. Pubertal stage and pubertal hormones uniquely contribute more …

Quantifying Brain Development In The Healthy Brain And Child Development (Hbcd) Study: The Magnetic Resonance Imaging And Spectroscopy Protocol, Douglas C Dean 3rd, Chad M Sylvester, Michael P Harms, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition …

Effect Of Screw Length In Volar Plating For Intra-Articular Distal Radius Fractures: A Biomechanical Study, Thomas S Hong, Daniel J Lee, Babak Jahani, Kaitlyn S Broz, Donald A Aboytes, Simon Tang, Stephen Demartini, David M Brogan

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to compare the effect of varying screw lengths on load to failure and retention of the dorsal ulnar corner fragment after fixation of comminuted intra-articular distal radius fractures in a cadaveric model.

METHODS: Twenty-four fresh frozen cadaveric forearms were subjected to a standardized distal radius osteotomy to mimic an intra-articular fracture pattern. Dual X-ray absorptiometry scans were performed to ensure minimal variability in bone density. All fractures were fixed with a volar locking plate and distal locking screws. Three different lengths of distal locking screws were used in each group of eight specimens …

Molecular Imaging In Experimental Pulmonary Fibrosis Reveals That Nintedanib Unexpectedly Modulates Ccr2 Immune Cell Infiltration, Hasan Farooq, Hannah P Luehmann, Jeffrey R Koenitzer, Gyu Seong Heo, Deborah H Sultan, Devesha H Kulkarni, Sean P Gunsten, Rekha M Sashti, Tao Huang, Amanda R Keller, Kory J Lavine, Jeffrey J Atkinson, Laura M Wingler, Yongjian Liu, Steven L Brody

2020-Current year OA Pubs

BACKGROUND: Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.

METHODS: Inhibition of CCR2+ cells and, as a benchmark, the clinical antifibrotic agent, nintedanib, were used in mouse lung fibrosis models. Lungs were evaluated directly for CCR2+ cell …

A Genetically Inducible Endothelial Niche Enables Vascularization Of Human Kidney Organoids With Multilineage Maturation And Emergence Of Renin Expressing Cells, Joseph C Maggiore, Haojia Wu, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. …

Mucosal Single-Cell Profiling Of Crohn's-Like Disease Of The Pouch Reveals Unique Pathogenesis And Therapeutic Targets, Siyan Cao, Khai M Nguyen, Kaiming Ma, Xiaotang Du, Xiuli Liu, Alina Ulezko Antonova, Richard P Rood, Anas Gremida, Chien-Huan Chen, Alexandra Gutierrez, Deborah C Rubin, Martin H Gregory, Mate Gergely, Guadalupe Oliva Escudero, Katherine Huang, Natalia Jaeger, Marina Cella, Rodney D Newberry, Nicholas O Davidson, Matthew A Ciorba, Parakkal Deepak, Marco Colonna

2020-Current year OA Pubs

BACKGROUND & AIMS: The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses.

METHODS: Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

2020-Current year OA Pubs

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Acral Fibrochondromyxoid Tumor: A Clinicopathologic And Molecular Genetic Study Of 37 Cases, Carina A Dehner, Jonathan C Baker, John S A Chrisinger, Et Al.

2020-Current year OA Pubs

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that …

Incident Cardiovascular Disease Risk Among Older Asian, Native Hawaiian And Pacific Islander Liver Cancer Survivors, Jing Wang, Yancen Pan, Chun-Pin Esther Chang, Anees Daud, Randa Tao, Mia Hashibe

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is a significant global health concern, particularly among Asian, Native Hawaiian, and Pacific Islander (ANHPI) communities that face unique health challenges. Liver cancer disproportionately affects ANHPI populations and has intricate associations with CVD risks due to shared pathophysiological mechanisms and metabolic disturbances. However, the specific CVD risk profile of ANHPI liver cancer patients remains poorly understood.

METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified and matched 1150 ANHPI and 2070 Non-Hispanic White (NHW) liver cancer patients diagnosed between 2000 and 2017. We used the Fine-Gray sub-distribution hazard model to estimate hazard ratios (HRs) …

Identifying Dose Constraints For The Parotid Ducts To Minimize Patient-Reported Xerostomia: Is Conventional Mean Dose Sparing Of The Parotid Glands Sufficient?, Manal Ahmidouch, Shiva K Das, Tong Zhu, Colette Shen, Lawrence B Marks, Bhishamjit S Chera, David V Fried

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The aim of this study was to identify dose constraints for the parotid ducts that limit patient-reported xerostomia and estimate whether these constraints are achieved during conventional parotid gland sparing radiation therapy (PGS-RT).

METHODS AND MATERIALS: Thirty-eight oropharyngeal squamous cell carcinoma patients were treated prospectively on trial with MRI sialography-guided parotid duct sparing radiation therapy (PDS-RT). PDS-RT explicitly minimizes dose to the parotid ducts in addition to PGS-RT. Parotid duct dose constraints were identified that distinguished patients reporting high and low rates of xerostomia. Atlas-based parotid duct contours were generated on a retrospective cohort of similar patients …

Subcutaneous Ocrelizumab In Multiple Sclerosis: Results Of The Phase 1b Ocarina I Study, Scott D Newsome, Robert T Naismith, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).

METHODS: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 …

Fibrolytic Vaccination Against Adam12 Reduces Desmoplasia In Preclinical Pancreatic Adenocarcinomas, Jing Chen, David Denardo, Et Al.

2020-Current year OA Pubs

A hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12

Analysis Of 1386 Epileptogenic Brain Lesions Reveals Association With Dyrk1a And Egfr, Christian M Boßelmann, Costin Leu, Tobias Brünger, Lucas Hoffmann, Sara Baldassari, Mathilde Chipaux, Roland Coras, Katja Kobow, Hajo Hamer, Daniel Delev, Karl Rössler, Christian G Bien, Thilo Kalbhenn, Tom Pieper, Till Hartlieb, Kerstin Becker, Lisa Ferguson, Robyn M Busch, Stéphanie Baulac, Peter Nürnberg, Imad Najm, Ingmar Blümcke, Dennis Lal

Faculty, Staff and Student Publications

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing. Here we confirm four known associations (BRAF, SLC35A2, MTOR, PTPN11), support eight associations without prior statistical support (FGFR1, PIK3CA, AKT3, NF1, PTEN, RHEB, KRAS, NRAS), and identify novel associations for two genes, …

Crosstalk Of Pyroptosis And Cytokine In The Tumor Microenvironment: From Mechanisms To Clinical Implication, Hua Wang, Tao Wang, Shuxiang Yan, Jinxin Tang, Yibo Zhang, Liming Wang, Haodong Xu, Chao Tu

Faculty, Staff and Student Publications

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex …

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children's TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff …

Akt Kinases As Therapeutic Targets, Dalal Hassan, Craig Menges, Joseph Testa, Alfonso Bellacosa

Student Papers, Posters & Projects

AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While …

De-Identification Is Not Enough: A Comparison Between De-Identified And Synthetic Clinical Notes, Atiquer Rahman Sarkar, Yao-Shun Chuang, Noman Mohammed, Xiaoqian Jiang

Faculty, Staff and Student Publications

For sharing privacy-sensitive data, de-identification is commonly regarded as adequate for safeguarding privacy. Synthetic data is also being considered as a privacy-preserving alternative. Recent successes with numerical and tabular data generative models and the breakthroughs in large generative language models raise the question of whether synthetically generated clinical notes could be a viable alternative to real notes for research purposes. In this work, we demonstrated that (i) de-identification of real clinical notes does not protect records against a membership inference attack, (ii) proposed a novel approach to generate synthetic clinical notes using the current state-of-the-art large language models, (iii) evaluated …

A Tetramer Of Bcl11a Is Required For Stable Protein Production And Fetal Hemoglobin Silencing, Ge Zheng, Maolu Yin, Stuti Mehta, I-Te Chu, Stacy Wang, Alia Alshaye, Kirstin Drainville, Altantsetseg Buyanbat, Frédérique Bienfait, Karin Tenglin, Qian Zhu, Stuart H Orkin

Faculty, Staff and Students Publications

Down-regulation of BCL11A protein reverses the fetal (HbF, α2γ2) to adult (HbA, α2β2) hemoglobin switch and is exploited in gene-based therapy for hemoglobin disorders. Due to reliance on ex vivo cell manipulation and marrow transplant, such therapies cannot lessen disease burden. To develop novel small molecule approaches, we interrogated the state of BCL11A protein in erythroid cells. We report that tetramer formation mediated by a single zinc-finger (ZnF0) is required for production of steady-state protein. Beyond its role in protein stability, the tetramer state is necessary for γ-globin gene repression, as an engineered monomer fails to engage a critical corepressor …

Building Capacity In Dissemination And Implementation Research: The Presence And Impact Of Advice Networks, Allison J L'Hotta, Rebekah R Jacob, Stephanie Mazzucca-Ragan, Russell E Glasgow, Sharon E Straus, Wynne E Norton, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: As dissemination and implementation (D&I) research increases, we must continue to expand training capacity and research networks. Documenting, understanding, and enhancing advice networks identifies key connectors and areas where networks are less established. In 2012 Norton et al. mapped D&I science advice and collaboration networks. The current study builds on this work and aims to map current D&I research advice networks.

METHODS: D&I researchers in the United States (US) and Canada were identified through a combination of publication metrics, and key persons identified networks and were invited to participate (n = 1,576). In this social network analysis study, participants …

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …

Context, Mechanisms And Community Engagement In Implementation Strategies: A Systematic Review Protocol Of Implementation Strategies Designed Using Implementation Mapping, Eunyoung Kang, Gill Ten Hoor, Derek W Craig, Serena Rodriguez, Jennifer Stockton, Maria E Fernandez

Faculty, Staff and Student Publications

INTRODUCTION: Implementation Mapping (IM) has increasingly been used for the design and/or selection and tailoring implementation strategies to promote the effective translation of evidence-based interventions into practice. IM is a tool for guiding the systematic, iterative, step-by-step design process that helps guide the co-creation of theory-based, evidence-informed implementation strategies. This protocol aims to describe the methods of the planned systematic review that will (1) examine the overall landscape of IM in developing implementation strategies, (2) explore the mechanisms of implementation strategies developed using IM and (3) investigate the use of IM and community engagement in the development of implementation strategies. …

Complement Immune System In Pulmonary Hypertension-Cooperating Roles Of Circadian Rhythmicity In Complement-Mediated Vascular Pathology, Hunter Devaughn, Haydn E Rich, Anthony Shadid, Priyanka K Vaidya, Marie-Francoise Doursout, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

Originally discovered in the 1890s, the complement system has traditionally been viewed as a "compliment" to the body's innate and adaptive immune response. However, emerging data have shown that the complement system is a much more complex mechanism within the body involved in regulating inflammation, gene transcription, attraction of macrophages, and many more processes. Sustained complement activation contributes to autoimmunity and chronic inflammation. Pulmonary hypertension is a disease with a poor prognosis and an average life expectancy of 2-3 years that leads to vascular remodeling of the pulmonary arteries; the pulmonary arteries are essential to host homeostasis, as they divert …

Blood Matters: The Hematological Signatures Of Coronavirus Infection, Ayelen Toro, Ana P Arévalo, Marianoel Pereira-Gómez, Agustina Sabater, Eric A Zizzi, Paula Perbolianachis, Gaston Pascual, Sofia Lage-Vickers, Jorge L Pórfido, Ines Achinelli, Rocio Seniuk, Juan Bizzotto, Pablo Sanchis, Alvaro Olivera, Alejandro Leyva, Pilar Moreno, Alicia Costábile, Alvaro Fajardo, Federico Carrión, Martín Fló, Natalia Olivero-Deibe, Fernando Rodriguez, Nicolas Nin, Nicolas Anselmino, Estefania Labanca, Elba Vazquez, Javier Cotignola, Daniel F Alonso, Maria P Valacco, Marcelo Marti, Francesco Gentile, Artem Cherkasov, Martina Crispo, Gonzalo Moratorio, Geraldine Gueron

Faculty, Staff and Student Publications

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, …