Digital Commons Network^™

Effect Of A Digital Health Exercise Program On The Intention For Spinal Surgery In Adult Spinal Deformity: Exploratory Cross-Sectional Survey, Marsalis Christian Brown, Christopher Quincy Lin, Christopher Jin, Matthew Rohde, Brett Rocos, Jonathan Belding, Barrett I. Woods, Stacey J. Ackerman

Rothman Institute Papers

BACKGROUND: Adult spinal deformity (ASD) is a prevalent condition estimated at 38%. Symptomatic ASD is associated with substantial health care costs. The role of nonoperative interventions in the management of ASD remains elusive. The National Scoliosis Clinic's (NSC) scoliosis realignment therapy (SRT) is a personalized digital health exercise program for the nonoperative management of ASD.

OBJECTIVE: This exploratory study had two objectives: (1) to evaluate the effect of the SRT program on users' intention of having spinal fusion; and (2) from a US payer perspective, to estimate the annual cost savings per 100,000 beneficiaries by averting spinal surgery.

METHODS: Individuals …

An Intranasally Administered Igm Protects Against Antigenically Distinct Subtypes Of Influenza A Viruses, Ashwin Kumar Ramesh, Jwala Priyadarsini Sivaccumar, Xiaohua Ye, Luona Yang, Hailong Guo, Chen-Ni Chin, Sha Ha, John W Shiver, William R Strohl, Yan Xu, Haijuan Du, Tongqing Zhou, Ningyan Zhang, Kai Xu, Xinli Liu, Tong-Ming Fu, Zhiqiang An

Faculty, Staff and Student Publications

Engineering broadly neutralizing monoclonal antibodies (mAbs) targeting the hemagglutinin (HA) of Influenza A virus (IAV) is a promising approach for intervention of seasonal flu. However, HA plasticity often leads to resistant strains that compromise mAb potency as bivalent IgGs. Here we hypothesize that multimerization of anti-IAV antibodies as IgMs can enhance coverage and neutralization potency. Here, we construct 18 IgM antibodies from known broadly neutralizing IgGs targeting different IAV HA epitopes and evaluate their breadth and potency of neutralization against distinct H1N1 and H3N2 IAVs. The IgM version of receptor binding site-specific IgG F045-092 shows increased breadth and antiviral potency …

Mapping The Developmental Profile Of Ventricular Zone-Derived Neurons In The Human Cerebellum, Anders W Erickson, Henry Tan, Liam D Hendrikse, Jake Millman, Zachary Thomson, Joseph Golser, Omar Khan, Guanyi He, Kathleen Bach, Arpit Suresh Mishra, Janja Kopic, Zeljka Krsnik, Ferechte Encha-Razavi, Giulia Petrilli, Fabien Guimiot, Evelina Silvestri, Kimberly A Aldinger, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human …

A Secretome Atlas Of Cardiac Fibroblasts From Healthy And Infarcted Mouse Hearts, Jasmin Bahr, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of …

Percutaneous Transluminal Angioplasty And Stenting (Ptas) In Patients With Symptomatic Intracranial Vertebrobasilar Artery Stenosis (Ivbs), Ramtin Pourahmad, Kiarash Saleki, Sina Zoghi, Ramtin Hajibeygi, Hamed Ghorani, Amin Javanbakht, Sina Goodarzi, Parsa Alijanizadeh, Kelly Trinh, Ravi Shastri, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Background: Approximately 20% of all transient ischaemic attacks (TIAs) and ischaemic strokes occur within the posterior circulation, with vertebrobasilar stenosis identified as the cause in roughly 25% of the cases. Studies have shown that about a quarter of these patients have atherosclerotic stenosis of at least 50% of the vertebrobasilar artery. Stenosis has been shown to be associated with an increased risk of 90-day recurrent vertebrobasilar stroke, particularly in the first few weeks, which is significantly higher when compared with patients with stenosis of the anterior circulation. Therefore, aggressive treatment is important for the patient's prognosis. Stenting is emerging as …

Rural-Urban Disparities In Hospitalisation For Myocardial Infarction In Systemic Lupus Erythematosus In The Usa, Jasvinder A Singh, Sumanth Chandrupatla

Faculty, Staff and Students Publications

Objective: To assess whether rural-urban disparities exist in people with SLE for hospitalisation with myocardial infarction (MI).

Methods: We used the 2016-2019 US National Inpatient Sample data that contain all hospitalisation data. In people with a diagnosis of SLE, we assessed the multivariable adjusted ORs (aORs) to examine the association of rural patient residence with MI hospitalisation, while adjusting for demographics, payer, income, hospital characteristics and the Deyo-Charlson Comorbidity Index.

Results: We found that the crude rates of patients hospitalised with MI per 100 000 area specific SLE hospitalisations were higher in rural versus urban residents with SLE, 2265 versus …

Intracellular And Extracellular Activities Of V-Domain Ig-Containing Suppressor Of T Cell Activation (Vista) Modulated By Immunosuppressive Factors Of Tumour Microenvironment, Maryam Abooali, Stephanie Schlichtner, Xi Lei, Nijas Aliu, Sabrina Ruggiero, Sonia Loges, Martin Ziegler, Franziska Hertel, Anna-Lena Volckmar, Albrecht Stenzinger, Petros Christopoulos, Michael Thomas, Elena Klenova, N Helge Meyer, Stergios Boussios, Nigel Heaton, Yoh Zen, Ane Zamalloa, Shilpa Chokshi, Luca Urbani, Sophie Richard, Kavitha Kirubendran, Rohanah Hussain, Giuliano Siligardi, Dietmar Cholewa, Steffen M Berger, Inna M Yasinska, Elizaveta Fasler-Kan, Vadim V Sumbayev

Peninsula Medical School

V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms of regulation of VISTA activity and functions by factors of tumour microenvironment (TME) remain unclear and understanding these processes is required in order to develop successful personalised cancer immunotherapeutic strategies and approaches. Here we report for the very first time that VISTA interacts with another immune checkpoint protein galectin-9 inside the cell most likely facilitating its interaction with TGF-β-activated kinase 1 (TAK1). This process is required for protection of lysosomes, which is crucial …

Heavy Metals In Spices From Lancaster, Pa: Arsenic, Cadmium, And Lead Exposure Risks And The Need For Regulation, Andrew Huff, Hoi Lam, Anuj Ghimirey, Jay Goldring, Michelle Pimentel, Harriet Okatch

College of Population Health Faculty Papers

Heavy metal exposure is associated with adverse health effects in children including impaired cognitive functioning. Studies have identified spices as a potential source of heavy metals. However, in Lancaster, PA no such studies have been conducted. Hence the aim of this study was to quantify arsenic (As), cadmium (Cd) and lead (Pb) in spices from Lancaster, PA. Spices were either purchased from stores in Lancaster or obtained as donations from families in Lancaster. As, Cd, and Pb were quantified using inductively coupled plasma-mass spectrometry. The Wilcoxon rank sum test was used to compare the median heavy metal concentrations in store-purchased …

Functional Connectivity Between The Visual And Salience Networks And Autistic Social Features At School-Age, Jessica B Girault, Tomoyuki Nishino, Muhamed Talović, Margaret Reynolds, Abraham Z Snyder, Kelly N Botteron, Natasha Marrus, Robert C Mckinstry, Alexandre A Todorov, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was …

The Potential Of Brain Organoids In Addressing The Heterogeneity Of Synucleinopathies, Xiao-Jun Diao, Claudio Soto, Fei Wang, Yu Wang, Yun-Cheng Wu, Abhisek Mukherjee

Faculty, Staff and Student Publications

Synucleinopathies are a group of diseases characterized by neuronal and glial accumulation of α-synuclein (aSyn) linked with different clinical presentations, including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Dementia with Lewy Bodies (DLB) and Multiple system atrophy (MSA). Interestingly, the structure of the aSyn aggregates can vary across different synucleinopathies. Currently, it is unclear how the aSyn protein can aggregate into diverse structures and affect distinct cell types and various brain regions, leading to different clinical symptoms. Recent advances in induced pluripotent stem cells (iPSCs)-based brain organoids (BOs) technology provide an unprecedented opportunity to define the etiology of synucleinopathies …

Investigative Needle Core Biopsies Support Multimodal Deep-Data Generation In Glioblastoma, Kenny K H Yu, Sreyashi Basu, Gerard Baquer, Ryuhjin Ahn, Jennifer Gantchev, Sonali Jindal, Michael S Regan, Zaki Abou-Mrad, Michael C Prabhu, Marc J Williams, Alicia D D'Souza, Seth W Malinowski, Kelsey Hopland, Yuval Elhanati, Sylwia A Stopka, Alexei Stortchevoi, Charles Couturier, Zhong He, Jingjing Sun, Yulong Chen, Alexsandra B Espejo, Kin Hoe Chow, Smitha Yerrum, Pei-Lun Kao, Brittany Parker Kerrigan, Lisa Norberg, Douglas Nielsen, Vinay K Puduvalli, Jason Huse, Rameen Beroukhim, Betty Y S Kim, Sangeeta Goswami, Adrienne Boire, Sarah Frisken, Michael J Cima, Matthias Holdhoff, Calixto-Hope G Lucas, Chetan Bettegowda, Stuart S Levine, Tejus A Bale, Cameron Brennan, David A Reardon, Frederick F Lang, E Antonio Chiocca, Keith L Ligon, Forest M White, Padmanee Sharma, Viviane Tabar, Nathalie Y R Agar

Faculty, Staff and Student Publications

Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the …

Place-Based Harms And Hidden Strengths: A Qualitative Study Exploring Facets Of Neighborhood Disinvestment Driving Opioid Overdose Among Black Individuals, Kaytryn D Campbell, Rachel P Winograd, Maria E Paschke, Alex Duello, Devin E Banks

2020-Current year OA Pubs

BACKGROUND: Despite significant efforts to address the opioid overdose crisis, Black people who use drugs (PWUD) face unabating, disproportionate increases in opioid overdose death (OOD) rates. These inequities persist in treatment admissions, utilization of medication for opioid use disorder, and treatment retention. Research has linked neighborhood disinvestment - a process of urban decline driven by policy-related changes in neighborhood demand and desirability leading to decreased population, physical and economic erosion, and poorer quality of life for residents - to increased rates of OOD. However, given recent increases in OOD inequities, more research is needed to determine the specific aspects of …

Improved Overall Survival In An Anti-Pd-L1 Treated Cohort Of Newly Diagnosed Glioblastoma Patients Is Associated With Distinct Immune, Mutation, And Gut Microbiome Features: A Single Arm Prospective Phase I/Ii Trial, Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V Damania, Mark Knafl, Brian Mckinley, Heather Lin, Rebecca A Harrison, Nazanin K Majd, Barbara J O'Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W K Alfred Yung, Luisa M Solis Soto, Dipen M Maru, Ignacio Wistuba, Edwin R Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A Wargo, Katja Schulze, Walter C Darbonne, Nadim J Ajami, Scott E Woodman, John F De Groot

Faculty, Staff and Student Publications

This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab and TMZ in newly diagnosed glioblastoma (GBM) patients and to identify pre-treatment correlates with outcome (N = 60). Trial number: NCT03174197. The primary outcome was overall survival (OS) whereas secondary outcomes were retrospective global-omics analyses to identify pre-treatment immune and genetic tumor features that correlated with survival. Concurrent use of atezolizumab with radiation and TMZ demonstrated OS in line with published trials for newly diagnosed GBM. Tumor genomic (WES and/or targeted NGS panel), transcriptomic (RNAseq) and tissue microenvironment …

Building A Pre-Surgical Multiparametric-Mri-Based Morphologic, Qualitative, Semiquantitative, First And High-Order Radiomic Predictive Treatment Response Model For Undifferentiated Pleomorphic Sarcoma To Replace Recist, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Robert S Benjamin, Jingfei Ma, Ken-Pin Hwang, R Jason Stafford, Dejka Araujo, Andrew J Bishop, Ravin Ratan, Wei-Lien Wang, Jossue Espinoza, Pia V Valenzuela, Chengyue Wu, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Background: Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response.

Methods: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves …

The Impact Of Epac2-Associated Junction Plakoglobin On Respiratory Syncytial Virus Infection, Chaitra A Takle, Eun-Jin Choi, Eun Seok Choi, Devang Deepak, Kashish Khatkar, Jong Min Choi, Ke Zhang, Sung Yun Jung, Tian Wang, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, …

Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al.

2020-Current year OA Pubs

Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Acute Brcaness Induction And Ar Pathway Blockage Through Cdk12/7/9 Degradation Enhances Parp Inhibitor Sensitivity In Prostate Cancer, Fu Gui, Baishan Jiang, Jie Jiang, Zhixiang He, Takuya Tsujino, Tomoaki Takai, Seiji Arai, Celine Pana, Jens Köllermann, Gary Andrew Bradshaw, Robyn Eisert, Marian Kalocsay, Anne Fassl, Steven P Balk, Adam S Kibel, Li Jia

Faculty, Staff and Student Publications

Current treatments for advanced prostate cancer (PCa) primarily target the androgen receptor (AR) pathway. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR pathway inhibitors (APPIs) remains ongoing challenges. Here, we present BSJ-5-63, a proteolysis-targeting chimera (PROTAC) targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, offering a multipronged approach to CRPC therapy. BSJ-5-63 degrades CDK12, diminishing BRCA1 and BRCA2 expression and inducing a sustained "BRCAness" state. This sensitizes cancer cells to PARP inhibitors (PARPis) regardless of their homologous recombination repair (HRR) status. Furthermore, CDK7 and CDK9 degradation attenuates AR signaling, enhancing its therapeutic efficacy. Preclinical studies, including …

A Pioneering Artificial Intelligence Tool To Predict Treatment Outcomes In Ovarian Cancer Via Diagnostic Laparoscopy, Xiaotian Ma, Yu-Chun Hsu, Amma Asare, Kai Zhang, Deanna Glassman, Katelyn F Handley, Katherine Foster, Khwahish Sharma, Shannon Westin, Amir Jazaeri, Nicole D Fleming, Pratip K Bhattacharya, Xiaoqian Jiang, Anil K Sood, Shayan Shams

Faculty, Staff and Student Publications

Ovarian cancer is associated with high rates of patient mortality and morbidity. Laparoscopic assessment of tumor localization can be used for treatment planning in newly diagnosed high-grade serous ovarian carcinoma (HGSOC). While spread to multiple intra-abdominal areas is correlated with worse outcomes, whether other morphological tumor differences are also associated with patient outcomes is unknown. Given the large volume of visual information in laparoscopic videos, we investigated whether deep-learning models can capture implicit features and predict treatment outcomes. We developed a novel deep-learning framework using pre-treatment laparoscopic images to assess clinical outcomes following upfront standard treatment, defined as short progression-free …

Spectrum Of Congenital Anomalies Detected Through Anatomy Ultrasound At A Referral Hospital In Ghana, Alim Swarray-Deen, Morgan Yapundich, Sarah Boudova, Kwaku Doffour-Dapaah, Jeff Osei-Agyapong, Perez Sepenu, Alex K. Boateng, Teresa A. Mensah, Patrick Anum, Nana Essuman Oduro, Theophilus Adu-Bredu, Promise E. Sefogah, Jerry Coleman, Samuel A. Oppong

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Africa has a high burden of congenital anomalies due in part to limited preconception care, infections, and environmental exposures. However, the true prevalence of congenital anomalies is unclear because of insufficient access to prenatal diagnostic services. We aimed to determine the rate of congenital anomalies, and characterize the anomalies detected prenatally at a referral hospital in Ghana.

METHODS: We performed a four-year retrospective review of all fetal anomaly ultrasounds performed and congenital anomalies detected from January 1st, 2020, to December 31st, 2023, at Korle Bu Teaching Hospital, Accra, Ghana. Data were extracted from the electronic database on maternal age, …

Deciphering Distinct Genetic Risk Factors For Ftld-Tdp Pathological Subtypes Via Whole-Genome Sequencing, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three …

Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez

2020-Current year OA Pubs

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of …

Investigating The Role Of Blood Models In Predicting Rupture Status Of Intracranial Aneurysms, Zonghan Lyu, Mostafa Rezaeitaleshmahalleh, Nan Mu, Jingfeng Jiang

Michigan Tech Publications

Purpose. Selecting patients with high-risk intracranial aneurysms (IAs) is of clinical importance. Recent work in machine learning-based (ML) predictive modeling has demonstrated that lesion-specific hemodynamics within IAs can be combined with other information to provide critical insights for assessing rupture risk. However, how the adoption of blood rheology models (i.e., Newtonian and Non-Newtonian blood models) may influence ML-based predictive modeling of IA rupture risk has not been investigated.Methods and Materials.In this study, we conducted transient CFD simulations using Newtonian and non-Newtonian rheology (Carreau-Yasuda [CY]) models on a large cohort of 'patient-specific' IA geometries (>100) under pulsatile flow conditions to …

The P130cas-Crk/Crkl Axis: A Therapeutic Target For Invasive Cancers Unveiled By Collaboration Among P130cas, Crk, And Crkl., Pegah Farhadi, Taeju Park

Manuscripts, Articles, Book Chapters and Other Papers

Numerous studies have documented the involvement of p130Cas (Crk-associated substrate) in a wide range of cellular processes across different types of cells. These processes encompass cell transformation, the connection between the extracellular matrix and the actin cytoskeleton, cell migration and invasion, and cardiovascular development. Moreover, p130Cas has been associated with the regulation of various physiological processes, including mammary, bone, brain, muscle, and liver homeostasis. The diverse functions of p130Cas can be attributed to its possession of multiple protein-protein interaction domains, which sets it apart as a unique class of adaptor protein. It is well established that p130Cas interacts critically with …

Implementation Of The Extension For Community Healthcare Outcomes Model For Hypertension Education Of Frontline Health Care Workers In The Federal Capital Territory, Nigeria: Explanatory Sequential Mixed Methods Evaluation, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was adapted for hypertension education of community health extension workers in the Federal Capital Territory, Nigeria, and delivered as a 7-part series.

OBJECTIVE: This study aims to evaluate implementation outcomes of the hypertension ECHO series mapped to the first 3 levels of the Kirkpatrick model. Outcomes included reach, appropriateness (level 1), effectiveness (level 2), and penetration (level 3).

METHODS: From August 2022 to April 2023, 7 hypertension ECHO sessions were delivered via Zoom (Zoom Video Communications, Inc) to a health care worker audience including targeted community health extension workers at 12 …

Difference In Clinical Presentation And Surgical Outcomes In Pediatric And Adult Patients With Chiari Malformation Type 1: A Single Center Retrospective Study, Erik Öhlén, Victor Gabriel El-Hajj, Victor E. Staartjes, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Chiari malformation type 1 (CM1) is a common congenital disorder affecting both children and adults. Although pediatric and adult CM1 patients share many characteristics, the differences between the groups are not fully described.

METHOD: A comparative analysis was made of two previously defined cohorts of adult and pediatric non-syndromic CM1, surgically treated at the study center. Clinical outcomes were assessed using the Chicago Chiari outcome scale (CCOS) and radiological outcomes were measured as change in cerebellar tonsil and syringomyelia status.

RESULTS: A total of 209 patients (73 pediatric, 136 adults) were included, with median ages of 11 and 33 …

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Idh Status Dictates Ohsv Mediated Metabolic Reprogramming Affecting Anti-Tumor Immunity, Upasana Sahu, Matthew P Mullarkey, Sara A Murphy, Joshua C Anderson, Vasanta Putluri, Abu Hena Mostafa Kamal, Jun Hyoung Park, Tae Jin Lee, Alexander L Ling, Benny A Kaipparettu, Ashok Sharma, Nagireddy Putluri, Pamela L Wenzel, Christopher D Willey, E Antonio Chiocca, James M Markert, Balveen Kaur

Faculty, Staff and Student Publications

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma. The switch in metabolism results in increased lipid synthesis and cellular ROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation and ferroptosis. Ferroptosis is critical to launch an …

Physical Activity Measurement Reactivity Among Midlife Adults With Elevated Risk For Cardiovascular Disease: Protocol For Coordinated Analyses Across Six Studies., Kiri Baga, Gabrielle M Salvatore, Iris Bercovitz, Amanda L Folk, Ria Singh, Laura M König, Meghan L Butryn, Jacqueline A Mogle, Danielle Arigo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United States, and adults aged 40-60 years with specific health conditions are at particularly elevated risk for developing CVD. Physical activity (PA) is a key cardioprotective behavior and many interventions exist to promote PA in this group. Effective promotion requires accurate assessment of PA behavior; as PA is often estimated by averaging across multiple days, a threat to accurate assessment is measurement reactivity, or an atypical increase in PA behavior at the start of measurement periods that may bias conclusions. Evidence for PA measurement reactivity is equivocal, though …

Virtual Reality-Enhanced Rehabilitation For Improving Musculoskeletal Function And Recovery After Trauma, Phani Paladugu, Rahul Kumar, Joshua Ong, Ethan Waisberg, Kyle Sporn

SKMC Student Presentations and Publications

Orthopedic trauma remains a critical challenge in modern healthcare, often resulting in severe mobility limitations, acute pain, and delayed recovery. Conventional rehabilitation techniques, though effective, fail to address the individualized, high-precision interventions needed for musculoskeletal injuries like fractures, joint instability, ligament tears, and muscular atrophy. Virtual reality (VR) technologies, such as Apple Vision Pro and HTC Vive Pro, offer a transformative approach by enhancing diagnostic precision, rehabilitation effectiveness, and patient engagement through interactive, immersive environments that improve clinical outcomes. These VR technologies provide real-time biomechanical data, such as joint mechanics, muscle coordination, and movement patterns, allowing clinicians to design personalized …