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2024

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Articles 3721 - 3750 of 9452

Full-Text Articles in Medical Specialties

Scanless Two-Photon Voltage Imaging, Ruth R Sims, Imane Bendifallah, Christiane Grimm, Aysha S Mohamed Lafirdeen, Soledad Domínguez, Chung Yuen Chan, Xiaoyu Lu, Benoît C Forget, François St-Pierre, Eirini Papagiakoumou, Valentina Emiliani Jun 2024

Scanless Two-Photon Voltage Imaging, Ruth R Sims, Imane Bendifallah, Christiane Grimm, Aysha S Mohamed Lafirdeen, Soledad Domínguez, Chung Yuen Chan, Xiaoyu Lu, Benoît C Forget, François St-Pierre, Eirini Papagiakoumou, Valentina Emiliani

Faculty, Staff and Students Publications

Two-photon voltage imaging has long been heralded as a transformative approach capable of answering many long-standing questions in modern neuroscience. However, exploiting its full potential requires the development of novel imaging approaches well suited to the photophysical properties of genetically encoded voltage indicators. We demonstrate that parallel excitation approaches developed for scanless two-photon photostimulation enable high-SNR two-photon voltage imaging. We use whole-cell patch-clamp electrophysiology to perform a thorough characterization of scanless two-photon voltage imaging using three parallel illumination approaches and lasers with different repetition rates and wavelengths. We demonstrate voltage recordings of high-frequency spike trains and sub-threshold depolarizations from neurons …


Contrast-Enhanced Magnetic Resonance Imaging Based T1 Mapping And Extracellular Volume Fractions Are Associated With Peripheral Artery Disease, Asem I Fitian, Michael C Shieh, Olga A Gimnich, Tatiana Belousova, Addison A Taylor, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner Jun 2024

Contrast-Enhanced Magnetic Resonance Imaging Based T1 Mapping And Extracellular Volume Fractions Are Associated With Peripheral Artery Disease, Asem I Fitian, Michael C Shieh, Olga A Gimnich, Tatiana Belousova, Addison A Taylor, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

BACKGROUND: Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis, but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1 mapping and ECV differ between PAD patients and matched controls.

METHODS AND RESULTS: A total of 37 individuals (18 PAD patients and 19 matched controls) underwent 3.0T CE-MRI. Skeletal calf muscle T1 mapping was performed before and after gadolinium contrast with a motion-corrected modified look-locker inversion recovery (MOLLI) pulse sequence. T1 values were calculated with a three-parameter Levenberg-Marquardt curve fitting algorithm. ECV and T1 maps were quantified …


Cardiac Magnetic Resonance In The Assessment Of The Anomalous Right Coronary Artery Originating From The Left Sinus Of Valsalva, Alberto Cipriani, Mauro Lo Rito, Silvia Pica, Monica De Gaspari, Ilaria Rigato, Martina Perazzolo Marra, Giorgio De Conti, Simone Corradin, Raffaella Motta, Valeria Pergola, Francesco Secchi, Massimo Lombardi, Barbara Bauce, Alessandro Zorzi, Gaetano Thiene, Cristina Basso, Silvana Molossi, Massimo Antonio Padalino, Domenico Corrado Jun 2024

Cardiac Magnetic Resonance In The Assessment Of The Anomalous Right Coronary Artery Originating From The Left Sinus Of Valsalva, Alberto Cipriani, Mauro Lo Rito, Silvia Pica, Monica De Gaspari, Ilaria Rigato, Martina Perazzolo Marra, Giorgio De Conti, Simone Corradin, Raffaella Motta, Valeria Pergola, Francesco Secchi, Massimo Lombardi, Barbara Bauce, Alessandro Zorzi, Gaetano Thiene, Cristina Basso, Silvana Molossi, Massimo Antonio Padalino, Domenico Corrado

Faculty, Staff and Students Publications

No abstract provided.


Viral And Host Factors Are Associated With Mortality In Hospitalized Patients With Covid-19, Neil R Aggarwal, Jacquie Nordwall, Dominique L Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A Ginde, Awori J Hayanga, Helene Highbarger, Mark Holodniy, Juan P Horcajada, Mamta K Jain, Kami Kim, Sylvain Laverdure, Jens Lundgren, Ven Natarajan, Hien H Nguyen, Sarah L Pett, Andrew Phillips, Garyphallia Poulakou, David A Price, Philip Robinson, Angela J Rogers, Uriel Sandkovsky, Katy Shaw-Saliba, Jeffrey M Sturek, Barbara W Trautner, Michael Waters, Cavan Reilly Jun 2024

Viral And Host Factors Are Associated With Mortality In Hospitalized Patients With Covid-19, Neil R Aggarwal, Jacquie Nordwall, Dominique L Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A Ginde, Awori J Hayanga, Helene Highbarger, Mark Holodniy, Juan P Horcajada, Mamta K Jain, Kami Kim, Sylvain Laverdure, Jens Lundgren, Ven Natarajan, Hien H Nguyen, Sarah L Pett, Andrew Phillips, Garyphallia Poulakou, David A Price, Philip Robinson, Angela J Rogers, Uriel Sandkovsky, Katy Shaw-Saliba, Jeffrey M Sturek, Barbara W Trautner, Michael Waters, Cavan Reilly

Faculty, Staff and Students Publications

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid …


Compassionate Curiosity: Mitigating The Effects Of Biasthrough Motivational Interviewing, Paul J. Hershberger, Dean A. Bricker, Angie Castle, Timothy N. Crawford, Stacy R. Flowers, Alexandria L. Goff, Katharine Conway Jun 2024

Compassionate Curiosity: Mitigating The Effects Of Biasthrough Motivational Interviewing, Paul J. Hershberger, Dean A. Bricker, Angie Castle, Timothy N. Crawford, Stacy R. Flowers, Alexandria L. Goff, Katharine Conway

Family Medicine Faculty Publications

There is strong evidence that the implicit biases of health care professionals affect the treatment of patients, and that minority and other marginalized patients are disproportionately harmed. Assumptions made about patient knowledge or lack thereof function as judgments that are prone to bias, which then affect the education and advice imposed upon patients. We review how the motivational interviewing (MI) approach to patient engagement includes components of evidence-based bias-mitigating strategies, such as understanding circumstances from the patient’s point of view, and therefore we propose that the MI approach can reduce the impact of bias in patient care.


Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley Jun 2024

Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley

Faculty, Staff and Student Publications

BACKGROUND: Adverse childhood experiences (ACEs) are potentially traumatic exposures experienced during childhood, for example, neglect. There is growing evidence that the coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic conditions contributed to an increased risk of ACEs. As public health programs/services are re-evaluated and restored following the state of emergency, it is important to plan using an ACEs-informed lens. The aim of this study was to identify and prioritize initiatives or activities that Public Health Ontario (PHO) could undertake to support Ontario public health units' work towards ACEs-informed pandemic recovery plans.

METHODS: The Child Health and Nutrition Research Initiative method …


Identifying Mage-A4-Positive Tumors For Tcr T Cell Therapies In Hla-A∗02-Eligible Patients, Tianjiao Wang, Jean-Marc Navenot, Stavros Rafail, Cynthia Kurtis, Mark Carroll, Marian Van Kerckhoven, Sofie Van Rossom, Kelly Schats, Konstantinos Avraam, Robyn Broad, Karen Howe, Ashley Liddle, Amber Clayton, Ruoxi Wang, Laura Quinn, Joseph P Sanderson, Cheryl Mcalpine, Carly Carozza, Eric Pimpinella, Susan Hsu, Francine Brophy, Erica Elefant, Paige Bayer, Dennis Williams, Marcus O Butler, Jeffrey M Clarke, Justin F Gainor, Ramaswamy Govindan, Victor Moreno, Melissa Johnson, Janet Tu, David S Hong, George R Blumenschein Jun 2024

Identifying Mage-A4-Positive Tumors For Tcr T Cell Therapies In Hla-A∗02-Eligible Patients, Tianjiao Wang, Jean-Marc Navenot, Stavros Rafail, Cynthia Kurtis, Mark Carroll, Marian Van Kerckhoven, Sofie Van Rossom, Kelly Schats, Konstantinos Avraam, Robyn Broad, Karen Howe, Ashley Liddle, Amber Clayton, Ruoxi Wang, Laura Quinn, Joseph P Sanderson, Cheryl Mcalpine, Carly Carozza, Eric Pimpinella, Susan Hsu, Francine Brophy, Erica Elefant, Paige Bayer, Dennis Williams, Marcus O Butler, Jeffrey M Clarke, Justin F Gainor, Ramaswamy Govindan, Victor Moreno, Melissa Johnson, Janet Tu, David S Hong, George R Blumenschein

Faculty, Staff and Student Publications

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across …


Ikzf1 And Ubr4 Gene Variants Drive Autoimmunity And Th2 Polarization In Igg4-Related Disease, Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, Abhinav Jain, Maryam Own, Qiankun Yang, Huimin Zhang, Filippo Pinto E Vairo, Karen Cerosaletti, Jane H Buckner, Kenneth J Warrington, Matthew J Koster, Cornelia M Weyand, Jörg J Goronzy Jun 2024

Ikzf1 And Ubr4 Gene Variants Drive Autoimmunity And Th2 Polarization In Igg4-Related Disease, Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, Abhinav Jain, Maryam Own, Qiankun Yang, Huimin Zhang, Filippo Pinto E Vairo, Karen Cerosaletti, Jane H Buckner, Kenneth J Warrington, Matthew J Koster, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, …


Identification And Characterization Of Cannabichromene's Major Metabolite Following Incubation With Human Liver Microsomes, Alexandra M Ward, Touraj Shokati, Jost Klawitter, Jelena Klawitter, Vu Nguyen, Laura Kozell, Atheir I Abbas, David Jones, Uwe Christians Jun 2024

Identification And Characterization Of Cannabichromene's Major Metabolite Following Incubation With Human Liver Microsomes, Alexandra M Ward, Touraj Shokati, Jost Klawitter, Jelena Klawitter, Vu Nguyen, Laura Kozell, Atheir I Abbas, David Jones, Uwe Christians

Faculty, Staff and Student Publications

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass …


Digital Gaming And Exercise Among Youth With Type 1 Diabetes: Cross-Sectional Analysis Of Data From The Type 1 Diabetes Exercise Initiative Pediatric Study., Susana R. Patton, Robin L. Gal, Simon Bergford, Peter Calhoun, Mark A. Clements, Jennifer L. Sherr, Michael C. Riddell Jun 2024

Digital Gaming And Exercise Among Youth With Type 1 Diabetes: Cross-Sectional Analysis Of Data From The Type 1 Diabetes Exercise Initiative Pediatric Study., Susana R. Patton, Robin L. Gal, Simon Bergford, Peter Calhoun, Mark A. Clements, Jennifer L. Sherr, Michael C. Riddell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Regular physical activity and exercise are fundamental components of a healthy lifestyle for youth living with type 1 diabetes (T1D). Yet, few youth living with T1D achieve the daily minimum recommended levels of physical activity. For all youth, regardless of their disease status, minutes of physical activity compete with other daily activities, including digital gaming. There is an emerging area of research exploring whether digital games could be displacing other physical activities and exercise among youth, though, to date, no studies have examined this question in the context of youth living with T1D.

OBJECTIVE: We examined characteristics of digital …


Durable Objective Response To Lurbinectedin In Small Cell Bladder Cancer With Tp53 Mutation: A Molecular-Directed Strategy, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Sagar A Naik, Vivek Subbiah, Matthew T Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi Jun 2024

Durable Objective Response To Lurbinectedin In Small Cell Bladder Cancer With Tp53 Mutation: A Molecular-Directed Strategy, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Sagar A Naik, Vivek Subbiah, Matthew T Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi

Faculty, Staff and Student Publications

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following …


Admission And Discharge Practices Among Assisted Living Communities: The Role Of State Regulations And Organizational Characteristics, Cassandra L. Hua, Lindsey Smith, Sheryl Zimmerman, Gauri Gadkari, Paula Carder, Philip D. Sloane, Christopher J. Wretman, Kali S. Thomas Jun 2024

Admission And Discharge Practices Among Assisted Living Communities: The Role Of State Regulations And Organizational Characteristics, Cassandra L. Hua, Lindsey Smith, Sheryl Zimmerman, Gauri Gadkari, Paula Carder, Philip D. Sloane, Christopher J. Wretman, Kali S. Thomas

Institute on Aging Publications

A better understanding of factors associated with assisted living admission and discharge practices can help identify communities that are more likely to allow residents to age in place. This study examined how state regulations and assisted living organizational characteristics relate to community admission and discharge practices for bathing, getting out of bed, and feeding.


Protocol For Improving Care By Faster Risk-Stratification Through Use Of High Sensitivity Point-Of-Care Troponin In Patients Presenting With Possible Acute Coronary Syndrome In The Emergency Department (Icare-Faster): A Stepped-Wedge Cluster Randomised Quality Improvement Initiative, John W Pickering, Gerard Devlin, Richard Body, Sally Aldous, Allan S Jaffe, Fred S Apple, Nicholas Mills, Richard W Troughton, Peter Kavsak, W Frank Peacock, Louise Cullen, Sarah J Lord, Christian Müller, Laura Joyce, Chris Frampton, Cameron James Lacey, Arthur M Richards, Suzanne Pitama, Martin Than Jun 2024

Protocol For Improving Care By Faster Risk-Stratification Through Use Of High Sensitivity Point-Of-Care Troponin In Patients Presenting With Possible Acute Coronary Syndrome In The Emergency Department (Icare-Faster): A Stepped-Wedge Cluster Randomised Quality Improvement Initiative, John W Pickering, Gerard Devlin, Richard Body, Sally Aldous, Allan S Jaffe, Fred S Apple, Nicholas Mills, Richard W Troughton, Peter Kavsak, W Frank Peacock, Louise Cullen, Sarah J Lord, Christian Müller, Laura Joyce, Chris Frampton, Cameron James Lacey, Arthur M Richards, Suzanne Pitama, Martin Than

Faculty, Staff and Students Publications

Introduction: Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an …


Development Of Biochemical And Cellular Probes To Study Ripk1 Target Engagement, Xin Yu, Hanfeng Lin, Feng Li, Jin Wang, Dong Lu Jun 2024

Development Of Biochemical And Cellular Probes To Study Ripk1 Target Engagement, Xin Yu, Hanfeng Lin, Feng Li, Jin Wang, Dong Lu

Faculty, Staff and Students Publications

RIPK1 inhibitors have emerged as promising candidates for treating diverse diseases, including inflammatory diseases, autoimmune disorders, Alzheimer’s disease, and cancer. However, the previously reported binding assays have limited sensitivity and stability, impeding high-throughput screening and robust characterization of the RIPK1 inhibitors. To address this challenge, we introduced two probes, T2-BDP-FL and T3-BDP-FL, derived from distinct RIPK1 inhibitors with different binding modes to establish time-resolved fluorescence resonance energy transfer (TR-FRET) displacement assays. Employing our TR-FRET displacement assays, we quantified the biochemical binding affinities of a series of RIPK1 inhibitors with diverse structural and binding modes for human RIPK1. Consistent results were …


Chagas Disease In Immunocompromised Patients, Eva H Clark, Louisa A Messenger, Jeffrey D Whitman, Caryn Bern Jun 2024

Chagas Disease In Immunocompromised Patients, Eva H Clark, Louisa A Messenger, Jeffrey D Whitman, Caryn Bern

Faculty, Staff and Students Publications

As Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various …


Obesity Severity Among Adolescents Presenting For Initial Evaluation To An Adolescent Weight Loss Surgery Program, Maria Cuccia, Alicia Wheelington, Hallie Kaplan, Grayce O'Neil, Sarah Barlow, Faisal Qureshi Jun 2024

Obesity Severity Among Adolescents Presenting For Initial Evaluation To An Adolescent Weight Loss Surgery Program, Maria Cuccia, Alicia Wheelington, Hallie Kaplan, Grayce O'Neil, Sarah Barlow, Faisal Qureshi

2024

No abstract provided.


Association Between Preoperative Patient Resilience And Patient-Reported Outcomes After Rotator Cuff Repair, Ryan W. Paul, Sydney Streicher, Matthew Wallingford, Michael P. Campbell, Adeeb J. Hanna, Sean Bryan, Fotios Tjoumakaris, Kevin Freedman Jun 2024

Association Between Preoperative Patient Resilience And Patient-Reported Outcomes After Rotator Cuff Repair, Ryan W. Paul, Sydney Streicher, Matthew Wallingford, Michael P. Campbell, Adeeb J. Hanna, Sean Bryan, Fotios Tjoumakaris, Kevin Freedman

Rothman Institute Papers

Background: Mental and emotional health can affect outcomes after orthopaedic surgery, and patient resilience has been found to be significantly related to postoperative functional outcomes. Purpose: To evaluate the relationship between preoperative patient resilience and 2-year postoperative patient-reported outcomes after rotator cuff repair (RCR). It was hypothesized that patients with low preoperative resilience will have worse patient-reported outcomes at 2 years after RCR versus those with high resilience. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary arthroscopic RCR in 2020 at a single institution and completed the Brief Resilience Scale (BRS) preoperatively were identified. Other …


The Polyaneuploid Cancer Cell State And Therapeutic Resistance: Eco-Evolutionary Dynamics In Structured Populations, Anuraag Bukkuri Jun 2024

The Polyaneuploid Cancer Cell State And Therapeutic Resistance: Eco-Evolutionary Dynamics In Structured Populations, Anuraag Bukkuri

USF Tampa Graduate Theses and Dissertations

In this dissertation, I develop and apply eco-evolutionary modeling techniques to understand how the polyaneuploid cancer cell (PACC) state, entered when aneuploid cells exit the cell cycle after S phase and undergo a whole genome duplication, contributes to therapeutic resistance. Since resistance remains one of the primary causes of treatment failure in cancer patients, it is critical to understand how such demographic state transitions allow for acclimatization of cancer cells to therapeutic stressors and how they interact with evolutionary processes to promote irreversible resistance.

In Chapters Two and Three, I lay the foundation for this work. In Chapter Two, I …


Rest-Dependent Downregulation Of Von Hippel-Lindau Tumor Suppressor Promotes Autophagy In Shh-Medulloblastoma, Ashutosh Singh, Donghang Cheng, Jyothishmathi Swaminathan, Yanwen Yang, Yan Zheng, Nancy Gordon, Vidya Gopalakrishnan Jun 2024

Rest-Dependent Downregulation Of Von Hippel-Lindau Tumor Suppressor Promotes Autophagy In Shh-Medulloblastoma, Ashutosh Singh, Donghang Cheng, Jyothishmathi Swaminathan, Yanwen Yang, Yan Zheng, Nancy Gordon, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella. In SHH medulloblastoma tumor xenografts, REST elevation is strongly correlated with increased expression of the hypoxia-inducible factor 1-alpha (HIF1α)-a positive regulator of autophagy, and with reduced expression of the von Hippel-Lindau (VHL) tumor suppressor protein - a …


Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski Jun 2024

Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski

Faculty, Staff and Student Publications

A laboratory-developed test (LDT) using analyte-specific reagents has been optimized on a commercial platform to detect macrolide resistance-associated mutations (MRM) in 23S rRNA from Mycoplasmoides genitalium from primary clinical specimens. In this study, MRM-LDT was applied to a multi-specimen source study set. One thousand four hundred ninety-five primary specimens testing positive for M. genitalium by commercial transcription-mediated amplification (TMA) were initially titered by the TMA assay using serial 10-fold dilutions to semi-quantitate target nucleic acid burden. Primary specimens were then processed for MRM detection using the MRM-LDT. Findings were stratified by gender and specimen source. The mean log10 target nucleic …


History Of Suicidal Behavior And Clozapine Prescribing Among People With Schizophrenia In China: A Cohort Study, Yi Yin, Chen Lin, Lijing Wei, Jinghui Tong, Junchao Huang, Baopeng Tian, Shuping Tan, Zhiren Wang, Fude Yang, Yongsheng Tong, Song Chen, L Elliot Hong, Yunlong Tan Jun 2024

History Of Suicidal Behavior And Clozapine Prescribing Among People With Schizophrenia In China: A Cohort Study, Yi Yin, Chen Lin, Lijing Wei, Jinghui Tong, Junchao Huang, Baopeng Tian, Shuping Tan, Zhiren Wang, Fude Yang, Yongsheng Tong, Song Chen, L Elliot Hong, Yunlong Tan

Faculty, Staff and Student Publications

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia.

METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information …


Digital Twin Mathematical Models Suggest Individualized Hemorrhagic Shock Resuscitation Strategies, Jeremy W Cannon, Danielle S Gruen, Ruben Zamora, Noah Brostoff, Kelly Hurst, John H Harn, Fayten El-Dehaibi, Zhi Geng, Rami Namas, Jason L Sperry, John B Holcomb, Bryan A Cotton, Jason J Nam, Samantha Underwood, Martin A Schreiber, Kevin K Chung, Andriy I Batchinsky, Leopoldo C Cancio, Andrew J Benjamin, Erin E Fox, Steven C Chang, Andrew P Cap, Yoram Vodovotz Jun 2024

Digital Twin Mathematical Models Suggest Individualized Hemorrhagic Shock Resuscitation Strategies, Jeremy W Cannon, Danielle S Gruen, Ruben Zamora, Noah Brostoff, Kelly Hurst, John H Harn, Fayten El-Dehaibi, Zhi Geng, Rami Namas, Jason L Sperry, John B Holcomb, Bryan A Cotton, Jason J Nam, Samantha Underwood, Martin A Schreiber, Kevin K Chung, Andriy I Batchinsky, Leopoldo C Cancio, Andrew J Benjamin, Erin E Fox, Steven C Chang, Andrew P Cap, Yoram Vodovotz

Faculty, Staff and Student Publications

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting.

METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation.

RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well …


Germ Cell Tumor Of The Testis: Lethal Subtypes Of A Curable Cancer, Jamaal C Jackson, Darren Sanchez, Andrew C Johns, Matthew T Campbell, Ahmet M Aydin, Neriman Gokden, Sanjay Maraboyina, Jason L Muesse, John F Ward, Louis L Pisters, Niki M Zacharias, Charles C Guo, Shi-Ming Tu Jun 2024

Germ Cell Tumor Of The Testis: Lethal Subtypes Of A Curable Cancer, Jamaal C Jackson, Darren Sanchez, Andrew C Johns, Matthew T Campbell, Ahmet M Aydin, Neriman Gokden, Sanjay Maraboyina, Jason L Muesse, John F Ward, Louis L Pisters, Niki M Zacharias, Charles C Guo, Shi-Ming Tu

Faculty, Staff and Student Publications

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection …


Small-Molecule Inhibition Of Kras Through Conformational Selection, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal Jun 2024

Small-Molecule Inhibition Of Kras Through Conformational Selection, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …


Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal Jun 2024

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …


Appropriateness Of Care: Deep Venous Procedures, Karem C. Harth Jun 2024

Appropriateness Of Care: Deep Venous Procedures, Karem C. Harth

Faculty Scholarship

In the past decade, technologies to treat venous pathologies have increased dramatically, to the benefit of an often underserved and overlooked population of patients with venous disease. However, given the rapid release of various technologies, including venous-dedicated stents and thrombectomy devices across varied venous pathologies, evidence-based guidelines have been slow to develop. When discussing appropriateness of care, one needs to consider optimal patient selection, technical approach, medical management, and surveillance protocols, to name a few. All of which, in the venous space, are currently widely varied in practice. The future of deep venous work is limitless, but multicenter, randomized controlled …


Bidirectional Needs Assessment Of Otolaryngology-Head And Neck Surgery Short-Term Surgical Trips In Zimbabwe, Katerina J. Green, Naboth Matinhira, Amiti Jain, Priya Arya, Dontre' M. Douse, Titus Dzongodza, Clemence Chidziva, Joshua P. Wiedermann Jun 2024

Bidirectional Needs Assessment Of Otolaryngology-Head And Neck Surgery Short-Term Surgical Trips In Zimbabwe, Katerina J. Green, Naboth Matinhira, Amiti Jain, Priya Arya, Dontre' M. Douse, Titus Dzongodza, Clemence Chidziva, Joshua P. Wiedermann

Student Papers, Posters & Projects

OBJECTIVES: To describe findings from an otolaryngology-specific needs assessment tool in Zimbabwe.

METHODS: Surveys were developed and shared with Low-Middle Income Country (LMIC) hosting institutions in Zimbabwe and to High-Income Country surgical trip participants (HIC). Respondents were otolaryngologists identified online and through professional networks who had participated in a surgical trip.

RESULTS: The most common procedures Zimbabwe otolaryngologists reported treating were adenotonsillectomy (85.7%), chronic rhinosinusitis (71.4%), chronic otitis (57.1%), and head and neck tumor intervention (57.1%). The most common untreatable conditions that host physicians wanted to treat were skull base surgery (71.4%), flap reconstructions (57.1%), and laryngotracheal reconstruction (57.1%). The …


Structural Analysis Of The Female Reptile Reproductive System By Micro-Computed Tomography And Optical Coherence Tomography†, Bonnie K Kircher, Michaela A Mccown, Deirdre M Scully, Richard R Behringer, Irina V Larina Jun 2024

Structural Analysis Of The Female Reptile Reproductive System By Micro-Computed Tomography And Optical Coherence Tomography†, Bonnie K Kircher, Michaela A Mccown, Deirdre M Scully, Richard R Behringer, Irina V Larina

Faculty, Staff and Student Publications

Volumetric data provide unprecedented structural insight to the reproductive tract and add vital anatomical context to the relationships between organs. The morphology of the female reproductive tract in non-avian reptiles varies between species, corresponding to a broad range of reproductive modes and providing valuable insight to comparative investigations of reproductive anatomy. However, reproductive studies in reptilian models, such as the brown anole studied here, have historically relied on histological methods to understand the anatomy. While these methods are highly effective for characterizing the cell types present in each organ, histological methods lose the 3D relationships between images and leave the …


Machine Learning In Time-Lapse Imaging To Differentiate Embryos From Young Vs Old Mice†, Liubin Yang, Carolina Leynes, Ashley Pawelka, Isabel Lorenzo, Andrew Chou, Brendan Lee, Jason D Heaney Jun 2024

Machine Learning In Time-Lapse Imaging To Differentiate Embryos From Young Vs Old Mice†, Liubin Yang, Carolina Leynes, Ashley Pawelka, Isabel Lorenzo, Andrew Chou, Brendan Lee, Jason D Heaney

Faculty, Staff and Students Publications

Time-lapse microscopy for embryos is a non-invasive technology used to characterize early embryo development. This study employs time-lapse microscopy and machine learning to elucidate changes in embryonic growth kinetics with maternal aging. We analyzed morphokinetic parameters of embryos from young and aged C57BL6/NJ mice via continuous imaging. Our findings show that aged embryos accelerated through cleavage stages (from 5-cells) to morula compared to younger counterparts, with no significant differences observed in later stages of blastulation. Unsupervised machine learning identified two distinct clusters comprising of embryos from aged or young donors. Moreover, in supervised learning, the extreme gradient boosting algorithm successfully …


Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland Jun 2024

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …