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Impact Of State Abortion Policies On Family Medicine Practice And Training After Dobbs V Jackson Women’S Health Organization, Karen L. Roper, Sarah Jane Robbins, Philip Day, Grace Shih, Neelima Kale Nov 2024

Impact Of State Abortion Policies On Family Medicine Practice And Training After Dobbs V Jackson Women’S Health Organization, Karen L. Roper, Sarah Jane Robbins, Philip Day, Grace Shih, Neelima Kale

UK CARES Faculty Publications

PURPOSE The Dobbs v Jackson Women’s Health Organization (Dobbs) Supreme Court decision revoked the constitutional right to abortion. Now, restrictive state abortion laws may con- tribute to the shortage and strain already felt in primary care practice, especially related to the provision of reproductive health care. The purpose of this study is to evaluate perceived impacts of state abortion legislation on family medicine clinicians’ practice and medical edu- cation regarding reproductive health care.

METHODS Ten questions were added to the 2022 Council of Academic Family Medicine Educational Research Alliance general membership survey to evaluate impact on relevant themes in reproductive …


Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag Nov 2024

Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

METHODS: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of …


Left, Then Right Internal Carotid Artery Dissection: A Case Report, Jeffrey M. Kalczynski, John Douds, Michael E. Silverman Nov 2024

Left, Then Right Internal Carotid Artery Dissection: A Case Report, Jeffrey M. Kalczynski, John Douds, Michael E. Silverman

SKMC Student Presentations and Publications

INTRODUCTION: We present a unique case of a patient who presented to the emergency department with stroke-like symptoms found to have a spontaneous, left-sided internal carotid artery dissection (ICAD).

CASE REPORT: The patient was treated successfully with thrombectomy and subsequently developed contralateral symptoms caused by a right-sided ICAD. This was managed with a second contra-lateral thrombectomy. The patient's course was complicated by persistent and mild hypotension, postulated to be secondary to bilateral carotid baroreceptor trauma from the dissections.

CONCLUSION: This case highlights the importance of close neurological monitoring for patients, preferably in a neurologic critical care setting, during and after …


Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk Nov 2024

Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk

Faculty, Staff and Student Publications

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, setting, and participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic …


Combined Single-Shot Intra-Articular Injection Of Ropivacaine And Contrast Media For Magnetic Resonance Imaging: Surgical Decision Making For Hip Arthroscopy In Young Patients, Neil Sarna, Gabriel I. Onor, Kathleen E. Schenker, Alvin W. Su Nov 2024

Combined Single-Shot Intra-Articular Injection Of Ropivacaine And Contrast Media For Magnetic Resonance Imaging: Surgical Decision Making For Hip Arthroscopy In Young Patients, Neil Sarna, Gabriel I. Onor, Kathleen E. Schenker, Alvin W. Su

Rothman Institute Papers

Introduction:

Hip impingement syndrome with labral tear is debilitating for young patients. When magnetic resonance arthrogram (MRA) is equivocal for surgical decision making, an additional intra-articular diagnostic injection (IA) can further confirm the diagnosis. We assessed the effectiveness on surgical decision making by combining hip MRA + IA in one single procedure.

Methods:

We conducted a retrospective review of a prospectively enrolled cohort of patients with hip impingement syndrome who underwent a combined MRA + IA procedure. A 10-mL cocktail containing 0.2% ropivacaine and Omnipaque 300 contrast media was injected into the hip joint, followed by magnetic resonance scanning, in …


Dementia Risk Reduction In The African Context: Multi-National Implementation Of Multimodal Strategies To Promote Healthy Brain Aging In Africa (The Africa-Fingers Project), Chinedu Momoh, Rachel Maina, Lukoye Atwoli, Karen Blackmon, Edna Bosire, Gloria Chemutai, Linda Khakali, Sylvia Mbugua, Zul Merali, Olivera Nesic Taylor,, Anthony Ngugi, Cyprian Mostert, Eunice Muthoni, Roselyter Riang’A, Mansoor Saleh, Shahin Sayed, Jasmit Shah Nov 2024

Dementia Risk Reduction In The African Context: Multi-National Implementation Of Multimodal Strategies To Promote Healthy Brain Aging In Africa (The Africa-Fingers Project), Chinedu Momoh, Rachel Maina, Lukoye Atwoli, Karen Blackmon, Edna Bosire, Gloria Chemutai, Linda Khakali, Sylvia Mbugua, Zul Merali, Olivera Nesic Taylor,, Anthony Ngugi, Cyprian Mostert, Eunice Muthoni, Roselyter Riang’A, Mansoor Saleh, Shahin Sayed, Jasmit Shah

Brain and Mind Institute

Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle-aged population, Africa presents a prime opportunity to implement evidence-based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa-FINGERS program offers an innovative solution, pioneering culturally sensitive, multidomain interventions tailored to the unique challenges of the region. Leveraging insights from landmark global studies such as Worldwide-FINGERS and Alzheimer's Disease Neuroimaging Initiative, the program employs a multideterminant precision prevention framework, grounded in community based systems dynamics. Africa-FINGERS further integrates cutting-edge state-of-the-art multimodal biomarker …


Anti-Egfr Aptamer Exhibits Direct Anti-Cancer Effects In Nsclc Cells Harboring Egfr L858r Mutations, Brian J. Thomas, Sania Z. Awan, Trupti Joshi, Mark A. Daniels, David Porciani, Donald H. Burke Nov 2024

Anti-Egfr Aptamer Exhibits Direct Anti-Cancer Effects In Nsclc Cells Harboring Egfr L858r Mutations, Brian J. Thomas, Sania Z. Awan, Trupti Joshi, Mark A. Daniels, David Porciani, Donald H. Burke

Biomedical Sciences

Non-small cell lung cancer (NSCLC) adenocarcinoma (LUAD) is a leading cause of death worldwide. Activating mutations in the tyrosine kinase domain of the oncogene epidermal growth factor receptor (EGFR) are responsible for ~10–50% of all LUAD cases. Although tyrosine kinase inhibitors (TKIs) have been effective in prolonging patient survival and quality of life, acquired resistance and disease progression are inevitable, presenting a clear unmet need for alternative or adjuvant therapeutics. Here we show that an anti-EGFR aptamer (EGFRapt) decreases viability and tumor growth of LUAD cell lines harboring the L858R ± T790M mutation in EGFR. Additionally, we elucidate …


Tfeb Controls Syncytiotrophoblast Formation And Hormone Production In Placenta, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Chiara Soldati, Margherita Mutarelli, Sandro Montefusco, Giuseppina Grieco, Lucia Vittoria Sepe, Barbara Rossi, Edoardo Nusco, Giada Rossignoli, Giorgia Panebianco, Fabrizio Merciai, Emanuela Salviati, Eduardo Maria Sommella, Pietro Campiglia, Graziano Martello, Davide Cacchiarelli, Diego Luis Medina, Andrea Ballabio Nov 2024

Tfeb Controls Syncytiotrophoblast Formation And Hormone Production In Placenta, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Chiara Soldati, Margherita Mutarelli, Sandro Montefusco, Giuseppina Grieco, Lucia Vittoria Sepe, Barbara Rossi, Edoardo Nusco, Giada Rossignoli, Giorgia Panebianco, Fabrizio Merciai, Emanuela Salviati, Eduardo Maria Sommella, Pietro Campiglia, Graziano Martello, Davide Cacchiarelli, Diego Luis Medina, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

TFEB, a bHLH-leucine zipper transcription factor belonging to the MiT/TFE family, globally modulates cell metabolism by regulating autophagy and lysosomal functions. Remarkably, loss of TFEB in mice causes embryonic lethality due to severe defects in placentation associated with aberrant vascularization and resulting hypoxia. However, the molecular mechanism underlying this phenotype has remained elusive. By integrating in vivo analyses with multi-omics approaches and functional assays, we have uncovered an unprecedented function for TFEB in promoting the formation of a functional syncytiotrophoblast in the placenta. Our findings demonstrate that constitutive loss of TFEB in knock-out mice is associated with defective formation of …


Increased Gremlin1 Expression In Pancreatic Ductal Adenocarcinoma Promotes A Fibrogenic Stromal Microenvironment, Rachel R Tindall, Erika Y Faraoni, Jiajing Li, Yinjie Zhang, Shun-Ming Ting, Beanna Okeugo, Xiurong Zhao, Yuying Liu, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Yanna Cao, Tien C Ko Nov 2024

Increased Gremlin1 Expression In Pancreatic Ductal Adenocarcinoma Promotes A Fibrogenic Stromal Microenvironment, Rachel R Tindall, Erika Y Faraoni, Jiajing Li, Yinjie Zhang, Shun-Ming Ting, Beanna Okeugo, Xiurong Zhao, Yuying Liu, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Yanna Cao, Tien C Ko

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not defined.

Materials and methods: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas RNA-sequencing data and characterized expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies.

Results: Grem1 expression is associated with an activated stroma and …


Increased White Blood Cell In Young Adults With Family Histories Of Alcohol And Other Substance Use Disorders, Mustafa N Mithaiwala, Nikki S Phillips, Dylan H Nguyen, Melanie S Beehler, Harrison S Ballard, Andrea S Vincent, William R Lovallo, Peter Kochunov, L Elliot Hong, Jason C O'Connor, Steve Cole, Ashley Acheson Nov 2024

Increased White Blood Cell In Young Adults With Family Histories Of Alcohol And Other Substance Use Disorders, Mustafa N Mithaiwala, Nikki S Phillips, Dylan H Nguyen, Melanie S Beehler, Harrison S Ballard, Andrea S Vincent, William R Lovallo, Peter Kochunov, L Elliot Hong, Jason C O'Connor, Steve Cole, Ashley Acheson

Faculty, Staff and Student Publications

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH-). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH- controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived …


Discovery, Characterization, And Structure Of A Cofactor-Independent Histidine Racemase From The Oral Pathogen Fusobacterium Nucleatum, Tess Lamer, Pu Chen, Marie J Venter, Marco J Van Belkum, Anjalee Wijewardane, Chenggang Wu, M Joanne Lemieux, John C Vederas Nov 2024

Discovery, Characterization, And Structure Of A Cofactor-Independent Histidine Racemase From The Oral Pathogen Fusobacterium Nucleatum, Tess Lamer, Pu Chen, Marie J Venter, Marco J Van Belkum, Anjalee Wijewardane, Chenggang Wu, M Joanne Lemieux, John C Vederas

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we …


Glymphatic Dysfunction In Multiple Sclerosis And Its Association With Disease Pathology And Disability, Ahmed Bayoumi, Khader M Hasan, Joseph A Thomas, Akram Yazdani, John A Lincoln Nov 2024

Glymphatic Dysfunction In Multiple Sclerosis And Its Association With Disease Pathology And Disability, Ahmed Bayoumi, Khader M Hasan, Joseph A Thomas, Akram Yazdani, John A Lincoln

Faculty, Staff and Student Publications

Background: The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function.

Objective: To evaluate glymphatic function in MS patients with lower and higher disability.

Methods: This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. …


Enterococcus Faecium: Evolution, Adaptation, Pathogenesis And Emerging Therapeutics, Yahan Wei, Dennise Palacios Araya, Kelli L. Palmer Nov 2024

Enterococcus Faecium: Evolution, Adaptation, Pathogenesis And Emerging Therapeutics, Yahan Wei, Dennise Palacios Araya, Kelli L. Palmer

School of Podiatric Medicine Publications

The opportunistic pathogen Enterococcus faecium colonizes humans and a wide range of animals, endures numerous stresses, resists antibiotic treatment and stubbornly persists in clinical environments. The widespread application of antibiotics in hospitals and agriculture has contributed to the emergence of vancomycin-resistant E. faecium, which causes many hospital-acquired infections. In this Review, we explore recent discoveries about the evolutionary history, the environmental adaptation and the colonization and dissemination mechanisms of E. faecium and vancomycin-resistant E. faecium. These studies provide critical insights necessary for developing novel preventive and therapeutic approaches against vancomycin-resistant E. faecium and also reveal the intricate interrelationships …


Shear Stress Induces A Time-Dependent Inflammatory Response In Human Monocyte-Derived Macrophages, Elysa Jui, Griffin Kingsley, Hong Kim T Phan, Kavya L Singampalli, Ravi K Birla, Jennifer P Connell, Sundeep G Keswani, K Jane Grande-Allen Nov 2024

Shear Stress Induces A Time-Dependent Inflammatory Response In Human Monocyte-Derived Macrophages, Elysa Jui, Griffin Kingsley, Hong Kim T Phan, Kavya L Singampalli, Ravi K Birla, Jennifer P Connell, Sundeep G Keswani, K Jane Grande-Allen

Faculty, Staff and Students Publications

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, …


Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Xin Zhou, Ying Wang, Zhangqi Dou, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti Nov 2024

Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Xin Zhou, Ying Wang, Zhangqi Dou, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells …


Bcl-Xl Is Translocated To The Nucleus Via Ctbp2 To Epigenetically Promote Metastasis, Tiantian Zhang, Sha Li, Yingcai Adrian Tan, Xiang Chen, Cheryl Zhang, Zhengming Chen, Bikash Mishra, Joseph Hyungjoon Na, Soyoung Choi, Sandra J Shin, Priyadarshan Damle, Kranthi Kumar Chougoni, Steven R Grossman, Dunrui Wang, Xuejun Jiang, Yi Li, Erika Hissong, Yao-Tseng Chen, Jenny Z Xiang, Yi-Chieh Nancy Du Nov 2024

Bcl-Xl Is Translocated To The Nucleus Via Ctbp2 To Epigenetically Promote Metastasis, Tiantian Zhang, Sha Li, Yingcai Adrian Tan, Xiang Chen, Cheryl Zhang, Zhengming Chen, Bikash Mishra, Joseph Hyungjoon Na, Soyoung Choi, Sandra J Shin, Priyadarshan Damle, Kranthi Kumar Chougoni, Steven R Grossman, Dunrui Wang, Xuejun Jiang, Yi Li, Erika Hissong, Yao-Tseng Chen, Jenny Z Xiang, Yi-Chieh Nancy Du

Faculty, Staff and Students Publications

Nuclear Bcl-xL is found to promote cancer metastasis independently of its mitochondria-based anti-apoptotic activity. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates histone H3 trimethyl Lys4 (H3K4me3) modification have yet to be understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds to Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced invasion and metastasis in mouse models. Furthermore, knockout of CtBP2 not only reduces the nuclear portion of Bcl-xL but also suppresses Bcl-xL transcription. The binding between Bcl-xL and …


A Cross-Systems Primer For Synthetic Microbial Communities, Elijah C Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P Partida-Martinez, Kathryn A Patras, Marie Simonin, Britt Koskella Nov 2024

A Cross-Systems Primer For Synthetic Microbial Communities, Elijah C Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P Partida-Martinez, Kathryn A Patras, Marie Simonin, Britt Koskella

Faculty, Staff and Students Publications

The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current …


Conservative Approach Versus Percutaneous Coronary Intervention In Patients With Spontaneous Coronary Artery Dissection From A National Population-Based Cohort Study, Chayakrit Krittanawong, Beatriz Castillo Rodriguez, Song Peng Ang, Yusuf Kamran Qadeer, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid Nov 2024

Conservative Approach Versus Percutaneous Coronary Intervention In Patients With Spontaneous Coronary Artery Dissection From A National Population-Based Cohort Study, Chayakrit Krittanawong, Beatriz Castillo Rodriguez, Song Peng Ang, Yusuf Kamran Qadeer, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare and often underdiagnosed cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. The management of SCAD remains a subject of debate, likely secondary to inconclusive evidence. This study aims to compare the clinical outcomes of SCAD patients treated with optimal medical therapy (OMT) versus those who underwent percutaneous coronary intervention (PCI) using a national population-based cohort.

METHODS: We conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2016 to 2020. The study included patients identified with SCAD using the ICD-10-CM (the International …


Suppression Of Matrigel-Induced Choroidal Neovascularization By Aav Delivery Of A Novel Anti-Scg3 Antibody, Chengchi Huang, Avinash Kaur, Liyang Ji, Hong Tian, Keith A Webster, Wei Li Nov 2024

Suppression Of Matrigel-Induced Choroidal Neovascularization By Aav Delivery Of A Novel Anti-Scg3 Antibody, Chengchi Huang, Avinash Kaur, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Efforts to develop gene therapy for long-term treatment of neovascular disease are hampered by ongoing concerns that biologics against vascular endothelial growth factor (VEGF) inhibit both physiological and pathological angiogenesis and are therefore at elevated risk of adverse side effects. A potential solution is to develop disease-targeted gene therapy. Secretogranin III (Scg3), a unique disease-restricted angiogenic factor described by our group, contributes significantly to ocular neovascular disease. We have shown that Scg3 blockade with a monoclonal antibody Fab fragment (Fab) stringently inhibits pathological angiogenesis without affecting healthy vessels. Here we tested the therapeutic efficacy of adeno-associated virus (AAV)-anti-Scg3Fab to block …


Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Joseph Weygand, Beata Gontova Bernat, Amanda M Jackson, Osama Mawlawi, Izabella Barreto, Yao Hao, Rao Khan, Afua A Yorke, William Swanson, Mohammed Saiful Huq, Eugene Lief, Cesar Della Biancia, Christopher F Njeh, Ahmad Al-Basheer, Oi Wai Chau, Stephen Avery, Wilfred Ngwa, Peter A Sandwall Nov 2024

Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Joseph Weygand, Beata Gontova Bernat, Amanda M Jackson, Osama Mawlawi, Izabella Barreto, Yao Hao, Rao Khan, Afua A Yorke, William Swanson, Mohammed Saiful Huq, Eugene Lief, Cesar Della Biancia, Christopher F Njeh, Ahmad Al-Basheer, Oi Wai Chau, Stephen Avery, Wilfred Ngwa, Peter A Sandwall

Faculty, Staff and Student Publications

Purpose: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders.

Methods and materials: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, …


Mechanisms Of Resistance To Oncogenic Kras Inhibition In Pancreatic Cancer, Julien Dilly, Megan T Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D Parent, Connor J Hennessey, Alexander C Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A Uribe, Annan Yang, Kevin S Kapner, Felix P Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M Lopez, Christopher A Bristow, Michael P Kim, Kimal I Rajapakshe, Vahid Bahrambeigi, Jennifer A Roth, Kavita Garg, Paola A Guerrero, Ben Z Stanger, Simona Cristea, Scott W Lowe, Timour Baslan, Eliezer M Van Allen, Joseph D Mancias, Emily Chan, Abraham Anderson, Yuliya V Katlinskaya, Alex K Shalek, David S Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P Heffernan, Seema Chugh, James G Christensen, Anirban Maitra, Brian M Wolpin, Srivatsan Raghavan, Jonathan A Nowak, Peter S Winter, Stephanie K Dougan, Andrew J Aguirre Nov 2024

Mechanisms Of Resistance To Oncogenic Kras Inhibition In Pancreatic Cancer, Julien Dilly, Megan T Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D Parent, Connor J Hennessey, Alexander C Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A Uribe, Annan Yang, Kevin S Kapner, Felix P Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M Lopez, Christopher A Bristow, Michael P Kim, Kimal I Rajapakshe, Vahid Bahrambeigi, Jennifer A Roth, Kavita Garg, Paola A Guerrero, Ben Z Stanger, Simona Cristea, Scott W Lowe, Timour Baslan, Eliezer M Van Allen, Joseph D Mancias, Emily Chan, Abraham Anderson, Yuliya V Katlinskaya, Alex K Shalek, David S Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P Heffernan, Seema Chugh, James G Christensen, Anirban Maitra, Brian M Wolpin, Srivatsan Raghavan, Jonathan A Nowak, Peter S Winter, Stephanie K Dougan, Andrew J Aguirre

Faculty, Staff and Student Publications

KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy. MRTX1133 treatment of the KrasLSL-G12D/+; Trp53LSL-R172H/+; p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, Cdk6, and Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. …


A Novel Statistical Framework For Meta-Analysis Of Total Mediation Effect With High-Dimensional Omics Mediators In Large-Scale Genomic Consortia, Zhichao Xu, Peng Wei Nov 2024

A Novel Statistical Framework For Meta-Analysis Of Total Mediation Effect With High-Dimensional Omics Mediators In Large-Scale Genomic Consortia, Zhichao Xu, Peng Wei

Faculty, Staff and Student Publications

Meta-analysis is used to aggregate the effects of interest across multiple studies, while its methodology is largely underexplored in mediation analysis, particularly in estimating the total mediation effect of high-dimensional omics mediators. Large-scale genomic consortia, such as the Trans-Omics for Precision Medicine (TOPMed) program, comprise multiple cohorts with diverse technologies to elucidate the genetic architecture and biological mechanisms underlying complex human traits and diseases. Leveraging the recent established asymptotic standard error of the R-squared (R2)-based mediation effect estimation for high-dimensional omics mediators, we have developed a novel meta-analysis framework requiring only summary statistics and allowing inter-study heterogeneity. Whereas the proposed …


A Complementary Metaproteomic Approach To Interrogate Microbiome Cultivated From Clinical Colon Biopsies, Van-An Duong, Altai Enkhbayar, Nobel Bhasin, Lakmini Senavirathna, Eva C Preisner, Kristi L Hoffman, Richa Shukla, Robert R Jenq, Kai Cheng, Mary P Bronner, Daniel Figeys, Robert A Britton, Sheng Pan, Ru Chen Nov 2024

A Complementary Metaproteomic Approach To Interrogate Microbiome Cultivated From Clinical Colon Biopsies, Van-An Duong, Altai Enkhbayar, Nobel Bhasin, Lakmini Senavirathna, Eva C Preisner, Kristi L Hoffman, Richa Shukla, Robert R Jenq, Kai Cheng, Mary P Bronner, Daniel Figeys, Robert A Britton, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic …


Microrna-1307-3p Contributes To Breast Cancer Progression Through Prm2, José Roberto Estupiñan-Jiménez, Valeria Villarreal-García, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejia, Jose Manuel Vazquez-Guillen, Patricio Adrián Zapata-Morin, Marienid Flores-Colón, Claudia Altamirano-Torres, Ezequiel Viveros-Valdez, Cristina Ivan, Mohammed H Rashed, Recep Bayraktar, Cristina Rodríguez-Padilla, Gabriel Lopez-Berestein, Diana Resendez-Perez Nov 2024

Microrna-1307-3p Contributes To Breast Cancer Progression Through Prm2, José Roberto Estupiñan-Jiménez, Valeria Villarreal-García, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejia, Jose Manuel Vazquez-Guillen, Patricio Adrián Zapata-Morin, Marienid Flores-Colón, Claudia Altamirano-Torres, Ezequiel Viveros-Valdez, Cristina Ivan, Mohammed H Rashed, Recep Bayraktar, Cristina Rodríguez-Padilla, Gabriel Lopez-Berestein, Diana Resendez-Perez

Faculty, Staff and Student Publications

Background: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR-1307-3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes.

Methods: Basal miR-1307-3p levels were quantified in BC cell lines MDA-MB-231 and MCF-7, as well as MCF-10A using quantitative real-time reverse transcription-PCR (RT-qPCR). The impact of miR-1307-3p inhibition on BC cell proliferation, migration, …


Fractionated Photoimmunotherapy Stimulates An Anti-Tumour Immune Response: An Integrated Mathematical And In Vitro Study, Mohammad U Zahid, Matthew Waguespack, Rebecca C Harman, Eric M Kercher, Shubhankar Nath, Tayyaba Hasan, Imran Rizvi, Bryan Q Spring, Heiko Enderling Nov 2024

Fractionated Photoimmunotherapy Stimulates An Anti-Tumour Immune Response: An Integrated Mathematical And In Vitro Study, Mohammad U Zahid, Matthew Waguespack, Rebecca C Harman, Eric M Kercher, Shubhankar Nath, Tayyaba Hasan, Imran Rizvi, Bryan Q Spring, Heiko Enderling

Faculty, Staff and Student Publications

Background: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.

Methods: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.

Results: In vitro measurements of PIT dose …


Mature Microrna-Binding Protein Qki Suppresses Extracellular Microrna Let-7b Release, Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon Nov 2024

Mature Microrna-Binding Protein Qki Suppresses Extracellular Microrna Let-7b Release, Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon

Faculty, Staff and Student Publications

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular …


Challenges In Diagnosing Nasopharyngeal Tumors, Alexandru Aristide Alexe, Mihai Victor Lupascu, Haldun Septar, Anca Pantea Stoian, Andra Iulia Suceveanu, Viorel Gherghina, Iuliana Cindea, Alina Doina Nicoara, Laura Mazilu, Razvan Hainarosie, Felix Voinea, Adrian Paul Suceveanu Oct 2024

Challenges In Diagnosing Nasopharyngeal Tumors, Alexandru Aristide Alexe, Mihai Victor Lupascu, Haldun Septar, Anca Pantea Stoian, Andra Iulia Suceveanu, Viorel Gherghina, Iuliana Cindea, Alina Doina Nicoara, Laura Mazilu, Razvan Hainarosie, Felix Voinea, Adrian Paul Suceveanu

Journal of Mind and Medical Sciences

Malignant nasopharyngeal tumors account for approximately 4% of ENT malignant tumor pathology and 1% of all cancers. The diagnosis of nasopharyngeal tumors is often late, the reason being the location in a silent anatomical region in terms of symptomatology and accessibility. Thus, approximately 70% of newly diagnosed patients with nasopharyngeal carcinoma unfortunately present with the condition in an advanced local stage. The early signs and symptoms are varied (nasal obstruction, hearing loss, otalgia, headache) and are usually ignored by the patient and even by the doctor in the initial stage of nasopharyngeal tumor evolution. Approximately 5% of patients have systemic …


A Geriatric Interprofessional Education Workshop: A Mixed Method Study, Patricia Watford, Meghan Hall, Colleen Hergott, Wanda Jirau-Rosaly, Shilpa Brown, Elena Wood, Nicole Rockich-Winston Oct 2024

A Geriatric Interprofessional Education Workshop: A Mixed Method Study, Patricia Watford, Meghan Hall, Colleen Hergott, Wanda Jirau-Rosaly, Shilpa Brown, Elena Wood, Nicole Rockich-Winston

Journal of Applied Disciplines

Interprofessional healthcare teams are essential for meeting the needs of our older population. To prepare for interprofessional collaboration, educational programs should offer opportunities for interprofessional education. We created a four-hour geriatric interprofessional workshop addressing cognition, macular degeneration, dysphagia, home safety, fall risk, and pharmacotherapy to examine student perceptions of working in interprofessional teams and their attitudes toward geriatric patients. Participants included 189 second-year medical (MD) students, 41 first-year occupational therapy (OT) students, and 36 second-year physical therapy (PT) students. We utilized a sequential explanatory mixed-method approach. Data analysis comprised descriptive statistics, paired t-tests for the pre/post surveys, and inductive content …


A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño Oct 2024

A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño

Faculty, Staff and Students Publications

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT …


Ten Challenges And Opportunities In Computational Immuno-Oncology, Riyue Bao, Alan Hutson, Anant Madabhushi, Vanessa D Jonsson, Spencer R Rosario, Jill S Barnholtz-Sloan, Elana J Fertig, Himangi Marathe, Lyndsay Harris, Jennifer Altreuter, Qingrong Chen, James Dignam, Andrew J Gentles, Edgar Gonzalez-Kozlova, Sacha Gnjatic, Erika Kim, Mark Long, Martin Morgan, Eytan Ruppin, David Van Valen, Hong Zhang, Natalie Vokes, Daoud Meerzaman, Song Liu, Eliezer M Van Allen, Yi Xing Oct 2024

Ten Challenges And Opportunities In Computational Immuno-Oncology, Riyue Bao, Alan Hutson, Anant Madabhushi, Vanessa D Jonsson, Spencer R Rosario, Jill S Barnholtz-Sloan, Elana J Fertig, Himangi Marathe, Lyndsay Harris, Jennifer Altreuter, Qingrong Chen, James Dignam, Andrew J Gentles, Edgar Gonzalez-Kozlova, Sacha Gnjatic, Erika Kim, Mark Long, Martin Morgan, Eytan Ruppin, David Van Valen, Hong Zhang, Natalie Vokes, Daoud Meerzaman, Song Liu, Eliezer M Van Allen, Yi Xing

Faculty, Staff and Student Publications

Immuno-oncology has transformed the treatment of cancer, with several immunotherapies becoming the standard treatment across histologies. Despite these advancements, the majority of patients do not experience durable clinical benefits, highlighting the imperative for ongoing advancement in immuno-oncology. Computational immuno-oncology emerges as a forefront discipline that draws on biomedical data science and intersects with oncology, immunology, and clinical research, with the overarching goal to accelerate the development of effective and safe immuno-oncology treatments from the laboratory to the clinic. In this review, we outline 10 critical challenges and opportunities in computational immuno-oncology, emphasizing the importance of robust computational strategies and interdisciplinary …