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Articles 11071 - 11100 of 26195
Full-Text Articles in Medicine and Health Sciences
Factors Affecting The Ability Of Patients With Complex Vascular Anomalies To Navigate The Healthcare System, Bryan Sisk, Sunny Lin, Anna M Kerr
Factors Affecting The Ability Of Patients With Complex Vascular Anomalies To Navigate The Healthcare System, Bryan Sisk, Sunny Lin, Anna M Kerr
2020-Current year OA Pubs
BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.
RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the …
Early Management Of Adult Traumatic Spinal Cord Injury In Patients With Polytrauma: A Consensus And Clinical Recommendations Jointly Developed By The World Society Of Emergency Surgery (Wses) & The European Association Of Neurosurgical Societies (Eans), Edoardo Picetti, Andreas Demetriades, Fausto Catena, Bizhan Aarabi, Fikri Abu-Zidan, Oscar Alves, Luca Ansaloni, Rocco Armonda, Rafael Badenes, Miklosh Bala, Zsolt J Balogh, Andrea Barbanera, Alessandro Bertuccio, Walter Biffl, Pierre Bouzat, Andras Buki, Ana Maria Castano-Leon, Davide Cerasti, Giuseppe Citerio, Federico Coccolini, Raul Coimbra, Carlo Coniglio, Francesco Costa, Federico De Iure, Bart Depreitere, Enrico Fainardi, Michael Fehlings, Nikolay Gabrovsky, Daniel Agustin Godoy, Peter Gruen, Deepak Gupta, Gregory Hawryluk, Raimund Helbok, Iftakher Hossain, Peter Hutchinson, Corrado Iaccarino, Kenji Inaba, Marcel Ivanov, Stanislav Kaprovoy, Andrew Kirkpatrick, Sam Klein, Angelos Kolias, Nikolay Konovalov, Alfonso Lagares, Laura Lippa, Angelica Loza-Gomez, Teemu Luoto, Andrew Maas, Andrzej Maciejczak, Ronald Maier, Niklas Marklund, Matthew Martin, Ilaria Melloni, Sergio Mendoza-Lattes, Geert Meyfroidt, Marina Munari, Lena Napolitano, David Okonkwo, Yasuhiro Otomo, Marios Papadopoulos, Ondra Petr, Wilco Peul, Aichholz K Pudkrong, Zaffer Qasim, Frank Rasulo, Carla Reizinho, Florian Ringel, Sandro Rizoli, Elham Rostami, Andres Rubiano, Emanuele Russo, Aarti Sarwal, Jan Schwab, Franco Servadei, Deepak Sharma, Salman Sharif, Ehab Shiban, Lori Shutter, Philip Stahel, Fabio Taccone, Nicole Terpolilli, Claudius Thomé, Peter Toth, Parmenion Tsitsopoulos, Andrew Udy, Alex Vaccaro, Albert Varon, Monica Vavilala, Alexander Younsi, Monika Zackova, Tommaso Zoerle, Chiara Robba
Early Management Of Adult Traumatic Spinal Cord Injury In Patients With Polytrauma: A Consensus And Clinical Recommendations Jointly Developed By The World Society Of Emergency Surgery (Wses) & The European Association Of Neurosurgical Societies (Eans), Edoardo Picetti, Andreas Demetriades, Fausto Catena, Bizhan Aarabi, Fikri Abu-Zidan, Oscar Alves, Luca Ansaloni, Rocco Armonda, Rafael Badenes, Miklosh Bala, Zsolt J Balogh, Andrea Barbanera, Alessandro Bertuccio, Walter Biffl, Pierre Bouzat, Andras Buki, Ana Maria Castano-Leon, Davide Cerasti, Giuseppe Citerio, Federico Coccolini, Raul Coimbra, Carlo Coniglio, Francesco Costa, Federico De Iure, Bart Depreitere, Enrico Fainardi, Michael Fehlings, Nikolay Gabrovsky, Daniel Agustin Godoy, Peter Gruen, Deepak Gupta, Gregory Hawryluk, Raimund Helbok, Iftakher Hossain, Peter Hutchinson, Corrado Iaccarino, Kenji Inaba, Marcel Ivanov, Stanislav Kaprovoy, Andrew Kirkpatrick, Sam Klein, Angelos Kolias, Nikolay Konovalov, Alfonso Lagares, Laura Lippa, Angelica Loza-Gomez, Teemu Luoto, Andrew Maas, Andrzej Maciejczak, Ronald Maier, Niklas Marklund, Matthew Martin, Ilaria Melloni, Sergio Mendoza-Lattes, Geert Meyfroidt, Marina Munari, Lena Napolitano, David Okonkwo, Yasuhiro Otomo, Marios Papadopoulos, Ondra Petr, Wilco Peul, Aichholz K Pudkrong, Zaffer Qasim, Frank Rasulo, Carla Reizinho, Florian Ringel, Sandro Rizoli, Elham Rostami, Andres Rubiano, Emanuele Russo, Aarti Sarwal, Jan Schwab, Franco Servadei, Deepak Sharma, Salman Sharif, Ehab Shiban, Lori Shutter, Philip Stahel, Fabio Taccone, Nicole Terpolilli, Claudius Thomé, Peter Toth, Parmenion Tsitsopoulos, Andrew Udy, Alex Vaccaro, Albert Varon, Monica Vavilala, Alexander Younsi, Monika Zackova, Tommaso Zoerle, Chiara Robba
Rothman Institute Papers
BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.
METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.
RESULTS: A total of 17 statements were …
Acetylcholine Receptor Based Chemogenetics Engineered For Neuronal Inhibition And Seizure Control Assessed In Mice, Katelyn N Benthall, Jillian Iafrati, Jesslyn Homidan, Jacob T Bendor, Barna Dudok, Jordan S Farrell, Tilo Gschwind, Charlotte L Porter, Annahita Keravala, G Steven Dodson, Ivan Soltesz
Acetylcholine Receptor Based Chemogenetics Engineered For Neuronal Inhibition And Seizure Control Assessed In Mice, Katelyn N Benthall, Jillian Iafrati, Jesslyn Homidan, Jacob T Bendor, Barna Dudok, Jordan S Farrell, Tilo Gschwind, Charlotte L Porter, Annahita Keravala, G Steven Dodson, Ivan Soltesz
Faculty, Staff and Students Publications
Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neuronal activity. We developed BARNI (Bradanicline- and Acetylcholine-activated Receptor for Neuronal Inhibition), an engineered channel comprised of the α7 nicotinic acetylcholine receptor ligand-binding domain coupled to an α1 glycine receptor anion pore domain. Here we demonstrate that BARNI activation by the clinical stage α7 nicotinic acetylcholine receptor-selective agonist bradanicline effectively suppressed targeted neuronal activity, and controlled both …
Causes, Functions, And Therapeutic Possibilities Of Rna Secondary Structure Ensembles And Alternative States
Faculty, Staff and Students Publications
RNA secondary structure plays essential roles in encoding RNA regulatory fate and function. Most RNAs populate ensembles of alternatively paired states and are continually unfolded and refolded by cellular processes. Measuring these structural ensembles and their contributions to cellular function has traditionally posed major challenges, but new methods and conceptual frameworks are beginning to fill this void. In this review, we provide a mechanism- and function-centric compendium of the roles of RNA secondary structural ensembles and minority states in regulating the RNA life cycle, from transcription to degradation. We further explore how dysregulation of RNA structural ensembles contributes to human …
Short Peripheral Blood Leukocyte Telomere Length In Rheumatoid Arthritis-Interstitial Lung Disease, Seoyeon Lee, Avram D Walts, Anthony Joseph Esposito, Sergio Poli, Ritu Gill, Hiroto Hatabu, Mizuki Nishino, Paul F Dellaripa, Michael E Weinblatt, Nancy A Shadick, M Kristen Demoruelle, Jeffrey A Sparks, Ivan O Rosas, Benjamin Granger, Kevin D Deane, Bruno Crestani, Paul J Wolters, Philippe Dieudé, Joyce S Lee
Short Peripheral Blood Leukocyte Telomere Length In Rheumatoid Arthritis-Interstitial Lung Disease, Seoyeon Lee, Avram D Walts, Anthony Joseph Esposito, Sergio Poli, Ritu Gill, Hiroto Hatabu, Mizuki Nishino, Paul F Dellaripa, Michael E Weinblatt, Nancy A Shadick, M Kristen Demoruelle, Jeffrey A Sparks, Ivan O Rosas, Benjamin Granger, Kevin D Deane, Bruno Crestani, Paul J Wolters, Philippe Dieudé, Joyce S Lee
Faculty, Staff and Students Publications
Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.
Obesity And Skeletal Fragility
Obesity And Skeletal Fragility
Faculty, Staff and Students Publications
Skeletal fracture has recently emerged as a complication of obesity. Given the normal or better than normal bone mineral density (BMD), the skeletal fragility of these patients appears to be a problem of bone quality rather than quantity. Type 2 diabetes mellitus (T2DM), the incidence of which increases with increasing body mass index, is also associated with an increased risk for fractures despite a normal or high BMD. With the additional bone pathology from diabetes itself, patients with both obesity and T2DM could have a worse skeletal profile. Clinically, however, there are no available methods for identifying those who are …
Causes, Functions, And Therapeutic Possibilities Of Rna Secondary Structure Ensembles And Alternative States
Faculty, Staff and Students Publications
RNA secondary structure plays essential roles in encoding RNA regulatory fate and function. Most RNAs populate ensembles of alternatively paired states and are continually unfolded and refolded by cellular processes. Measuring these structural ensembles and their contributions to cellular function has traditionally posed major challenges, but new methods and conceptual frameworks are beginning to fill this void. In this review, we provide a mechanism- and function-centric compendium of the roles of RNA secondary structural ensembles and minority states in regulating the RNA life cycle, from transcription to degradation. We further explore how dysregulation of RNA structural ensembles contributes to human …
Effect Of Testosterone Replacement Therapy On Sexual Function And Hypogonadal Symptoms In Men With Hypogonadism, A Michael Lincoff, Steven E Nissen, Mohit Khera, Michael G Miller, Panagiotis Flevaris, Xue Li, Kathleen Wannemuehler, Shalender Bhasin
Effect Of Testosterone Replacement Therapy On Sexual Function And Hypogonadal Symptoms In Men With Hypogonadism, A Michael Lincoff, Steven E Nissen, Mohit Khera, Michael G Miller, Panagiotis Flevaris, Xue Li, Kathleen Wannemuehler, Shalender Bhasin
Faculty, Staff and Students Publications
Context: Few long-term randomized trials have evaluated the efficacy of testosterone replacement therapy (TRT) in improving sexual function and hypogonadal symptoms in men with hypogonadism and whether effects are sustained beyond 12 months.
Objective: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. The Sexual Function Study, nested within the parent trial, determined testosterone's efficacy in improving sexual activity, hypogonadal symptoms, libido, and erectile function among men reporting low libido.
Methods: Among 5204 men, …
Pilot Implementation Of A Nutrition-Focused Community-Health-Worker Intervention Among Formerly Chronically Homeless Adults In Permanent Supportive Housing, Farrah Hmaidan, Clara Smith, Eva Thibaudeau-Graczyk, Shreela V Sharma
Pilot Implementation Of A Nutrition-Focused Community-Health-Worker Intervention Among Formerly Chronically Homeless Adults In Permanent Supportive Housing, Farrah Hmaidan, Clara Smith, Eva Thibaudeau-Graczyk, Shreela V Sharma
Faculty, Staff and Student Publications
Food insecurity is a known health equity threat for formerly chronically homeless populations even after they transition into permanent housing. This project utilized a human-centered design methodology to plan and implement a nutrition-focused community-health-worker (CHW) intervention in permanent supportive housing (PSH). The project aimed to increase access to healthy foods, improve nutritional literacy, healthy cooking/eating practices, and build community/social connectedness among 140 PSH residents. Validated food-security screening conducted by CHWs identified low or very low food security among 64% of 83 residents who completed the baseline survey, which is similar to rates found in a previous study among formerly homeless …
Equilibrium Points And Their Stability Of Covid-19 In Us, Henry H Lu, Li Jin, Momiao Xiong
Equilibrium Points And Their Stability Of Covid-19 In Us, Henry H Lu, Li Jin, Momiao Xiong
Faculty, Staff and Student Publications
This study aims to develop an advanced mathematic model and investigate when and how will the COVID-19 in the US be evolved to endemic. We employed a nonlinear ordinary differential equations-based model to simulate COVID-19 transmission dynamics, factoring in vaccination efforts. Multi-stability analysis was performed on daily new infection data from January 12, 2021 to December 12, 2022 across 50 states in the US. Key indices such as eigenvalues and the basic reproduction number were utilized to evaluate stability and investigate how the pandemic COVD-19 will evolve to endemic in the US. The transmissional, recovery, vaccination rates, vaccination effectiveness, eigenvalues …
Revealing Chronic Disease Progression Patterns Using Gaussian Process For Stage Inference, Hongyu Wang, Xiaobo Zhou
Revealing Chronic Disease Progression Patterns Using Gaussian Process For Stage Inference, Hongyu Wang, Xiaobo Zhou
Faculty, Staff and Student Publications
OBJECTIVE: The early stages of chronic disease typically progress slowly, so symptoms are usually only noticed until the disease is advanced. Slow progression and heterogeneous manifestations make it challenging to model the transition from normal to disease status. As patient conditions are only observed at discrete timestamps with varying intervals, an incomplete understanding of disease progression and heterogeneity affects clinical practice and drug development.
MATERIALS AND METHODS: We developed the Gaussian Process for Stage Inference (GPSI) approach to uncover chronic disease progression patterns and assess the dynamic contribution of clinical features. We tested the ability of the GPSI to reliably …
Identification Of Molecular Subphenotypes In Two Cohorts Of Paediatric Ards, Nadir Yehya, Matt S Zinter, Jill M Thompson, Michelle J Lim, Mark R Hanudel, Mustafa F Alkhouli, Hector Wong, Matthew N Alder, Daniel J Mckeone, E Scott Halstead, Pratik Sinha, Anil Sapru
Identification Of Molecular Subphenotypes In Two Cohorts Of Paediatric Ards, Nadir Yehya, Matt S Zinter, Jill M Thompson, Michelle J Lim, Mark R Hanudel, Mustafa F Alkhouli, Hector Wong, Matthew N Alder, Daniel J Mckeone, E Scott Halstead, Pratik Sinha, Anil Sapru
2020-Current year OA Pubs
BACKGROUND: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions.
METHODS: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers.
FINDINGS: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a …
Predicting Radiotherapy Patient Outcomes With Real-Time Clinical Data Using Mathematical Modelling, Alexander P Browning, Thomas D Lewin, Ruth E Baker, Philip K Maini, Eduardo G Moros, Helen M Byrne
Predicting Radiotherapy Patient Outcomes With Real-Time Clinical Data Using Mathematical Modelling, Alexander P Browning, Thomas D Lewin, Ruth E Baker, Philip K Maini, Eduardo G Moros, Helen M Byrne
Faculty, Staff and Student Publications
Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses. In this work, we present a compartment model of tumour volume and tumour composition, which, despite relative simplicity, is …
Polygenic Scores For Tobacco Use Provide Insights Into Systemic Health Risks In A Diverse Ehr-Linked Biobank In Los Angeles, Vidhya Venkateswaran, Kristin Boulier, Yi Ding, Ruth Johnson, Arjun Bhattacharya
Polygenic Scores For Tobacco Use Provide Insights Into Systemic Health Risks In A Diverse Ehr-Linked Biobank In Los Angeles, Vidhya Venkateswaran, Kristin Boulier, Yi Ding, Ruth Johnson, Arjun Bhattacharya
Faculty, Staff and Student Publications
Tobacco use is a major risk factor for many diseases and is heavily influenced by environmental factors with significant underlying genetic contributions. Here, we evaluated the predictive performance, risk stratification, and potential systemic health effects of tobacco use disorder (TUD) predisposing germline variants using a European- ancestry-derived polygenic score (PGS) in 24,202 participants from the multi-ancestry, hospital-based UCLA ATLAS biobank. Among genetically inferred ancestry groups (GIAs), TUD-PGS was significantly associated with TUD in European American (EA) (OR: 1.20, CI: [1.16, 1.24]), Hispanic/Latin American (HL) (OR:1.19, CI: [1.11, 1.28]), and East Asian American (EAA) (OR: 1.18, CI: [1.06, 1.31]) GIAs but …
Syphilis Complicating Pregnancy And Congenital Syphilis, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann
Syphilis Complicating Pregnancy And Congenital Syphilis, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann
Faculty, Staff and Student Publications
No abstract provided.
Enabling The Clinical Application Of Artificial Intelligence In Genomics: A Perspective Of The Amia Genomics And Translational Bioinformatics Workgroup, Robert R Freimuth, David B Everman, Derek C Walton, Scott P Mcgrath, Dominick J Lemas, Panayiotis V Benos, Alexander V Alekseyenko, Qianqian Song, Ece Gamsiz Uzun, Casey Overby Taylor, Alper Uzun, Thomas Nate Person, Nadav Rappoport, Zhongming Zhao, Marc S Williams
Enabling The Clinical Application Of Artificial Intelligence In Genomics: A Perspective Of The Amia Genomics And Translational Bioinformatics Workgroup, Robert R Freimuth, David B Everman, Derek C Walton, Scott P Mcgrath, Dominick J Lemas, Panayiotis V Benos, Alexander V Alekseyenko, Qianqian Song, Ece Gamsiz Uzun, Casey Overby Taylor, Alper Uzun, Thomas Nate Person, Nadav Rappoport, Zhongming Zhao, Marc S Williams
Faculty, Staff and Student Publications
OBJECTIVE: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space.
PROCESS: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members.
CONCLUSIONS: Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of …
Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu
Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu
Department of Pediatrics Faculty Papers
Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …
Using The R = Mc2 Heuristic To Understand Barriers To And Facilitators Of Implementing School-Based Physical Activity Opportunities: A Qualitative Study, Natalia I Heredia
Using The R = Mc2 Heuristic To Understand Barriers To And Facilitators Of Implementing School-Based Physical Activity Opportunities: A Qualitative Study, Natalia I Heredia
Faculty, Staff and Student Publications
BACKGROUND: Schools are a key setting for supporting youth physical activity, given their broad reach and diverse student populations. Organizational readiness is a precursor to the successful implementation of school-based physical activity opportunities. The R = MC
METHODS: We analyzed interview data from 15 elementary school staff (principals, assistant principals, physical education teachers, and classroom teachers) from a school district in Texas. We focused on factors related to adopting, implementing, and sustaining a variety of school-based physical activity opportunities. We used the Framework Method to guide the analysis and coded data using deductive (informed by the R = MC
RESULTS: …
Post-Exposure Intranasal Ifnα Suppresses Replication And Neuroinvasion Of Venezuelan Equine Encephalitis Virus Within Olfactory Sensory Neurons, Matthew D Cain, N Rubin Klein, Xiaoping Jiang, Hamid Salimi, Qingping Wu, Mark J Miller, William B Klimstra, Robyn S Klein
Post-Exposure Intranasal Ifnα Suppresses Replication And Neuroinvasion Of Venezuelan Equine Encephalitis Virus Within Olfactory Sensory Neurons, Matthew D Cain, N Rubin Klein, Xiaoping Jiang, Hamid Salimi, Qingping Wu, Mark J Miller, William B Klimstra, Robyn S Klein
2020-Current year OA Pubs
BACKGROUND: Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied.
METHODS: We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure.
RESULTS: We found that immature OSN, which …
Cdk4/6 Inhibition Sensitizes Intracranial Tumors To Pd-1 Blockade In Preclinical Models Of Brain Metastasis, Naema Nayyar, Magali A De Sauvage, Jane Chuprin, Emily M Sullivan, Mohini Singh, Britney S Zhang, Keith A Daniels, Christopher Alvarez-Breckenridge, Ashish Dahal, Michael A Brehm, Priscilla K Brastianos
Cdk4/6 Inhibition Sensitizes Intracranial Tumors To Pd-1 Blockade In Preclinical Models Of Brain Metastasis, Naema Nayyar, Magali A De Sauvage, Jane Chuprin, Emily M Sullivan, Mohini Singh, Britney S Zhang, Keith A Daniels, Christopher Alvarez-Breckenridge, Ashish Dahal, Michael A Brehm, Priscilla K Brastianos
Faculty, Staff and Student Publications
PURPOSE: Brain metastases are associated with high morbidity and are often resistant to immune checkpoint inhibitors. We evaluated whether CDK4/6 inhibitor (CDKi) abemaciclib can sensitize intracranial tumors to programmed cell death protein 1 (PD-1) inhibition in mouse models of melanoma and breast cancer brain metastasis.
EXPERIMENTAL DESIGN: Treatment response was evaluated in vivo using immunocompetent mouse models of brain metastasis bearing concurrent intracranial and extracranial tumors. Treatment effect on intracranial and extracranial tumor-immune microenvironments (TIME) was evaluated using immunofluorescence, multiplex immunoassays, high-parameter flow cytometry, and T-cell receptor profiling. Mice with humanized immune systems were evaluated using flow cytometry to study …
Pressing Need Of Precision Care In Her2-Positive Colorectal Cancer: The Elephant In The Room, Kanwal P S Raghav, Jonathan M Loree, Scott Kopetz
Pressing Need Of Precision Care In Her2-Positive Colorectal Cancer: The Elephant In The Room, Kanwal P S Raghav, Jonathan M Loree, Scott Kopetz
Faculty, Staff and Student Publications
Although dual HER2 inhibition has shown promising clinical activity in patients with RAS wild-type HER2-positive metastatic colorectal cancer, predictive biomarkers of response/resistance are less well characterized. Activating HER2/RTK/MAPK genomic alterations appears to blunt the clinical benefit of dual anti-HER2 therapy and may hold a potential albeit partial role in patient selection. See related article by Randon et al., p. 436.
Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Scott Evans, Robert K Ernst
Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Scott Evans, Robert K Ernst
Faculty, Staff and Student Publications
Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 …
Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au
Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au
Rowan-Virtua School of Osteopathic Medicine Departmental Research
BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.
METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive
CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …
Metabolomic Rewiring Promotes Endocrine Therapy Resistance In Breast Cancer, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu
Metabolomic Rewiring Promotes Endocrine Therapy Resistance In Breast Cancer, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu
Faculty, Staff and Students Publications
Approximately one-third of endocrine-treated women with estrogen receptor-alpha positive (ER+) breast cancers (BC) are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ BC to improve patient treatment. Mitochondrial fatty acid β-oxidation (FAO) has been shown to be a major metabolic pathway in triple-negative BC (TNBC) that can activate Src signaling. Here, we found metabolic reprogramming that increases FAO in ER+ BC as a mechanism of resistance to endocrine therapy. A metabolically relevant, integrated gene signature was derived from transcriptomic, metabolomic, and lipidomic analyses in …
The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Todd J Treangen, Tor C Savidge
The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Todd J Treangen, Tor C Savidge
Faculty, Staff and Students Publications
Targeted metagenomic sequencing is an emerging strategy to survey disease-specific microbiome biomarkers for clinical diagnosis and prognosis. However, this approach often yields inconsistent or conflicting results owing to inadequate study power and sequencing bias. We introduce Taxa4Meta, a bioinformatics pipeline explicitly designed to compensate for technical and demographic bias. We designed and validated Taxa4Meta for accurate taxonomic profiling of 16S rRNA amplicon data acquired from different sequencing strategies. Taxa4Meta offers significant potential in identifying clinical dysbiotic features that can reliably predict human disease, validated comprehensively via reanalysis of individual patient 16S data sets. We leveraged the power of Taxa4Meta's pan-microbiome …
Straight To The Point: Evaluation Of A Point Of Care Information (Poci) Resource In Answering Disease-Related Questions, Zoe Co, Aqsa Mugal, Angela Rui, Pamela M Garabedian, Marlika Marceau, Ania Syrowatka, Lynn A Volk, David W Bates
Straight To The Point: Evaluation Of A Point Of Care Information (Poci) Resource In Answering Disease-Related Questions, Zoe Co, Aqsa Mugal, Angela Rui, Pamela M Garabedian, Marlika Marceau, Ania Syrowatka, Lynn A Volk, David W Bates
Faculty, Staff and Students Publications
Objective: To evaluate the ability of DynaMedex, an evidence-based drug and disease Point of Care Information (POCI) resource, in answering clinical queries using keyword searches.
Methods: Real-world disease-related questions compiled from clinicians at an academic medical center, DynaMedex search query data, and medical board review resources were categorized into five clinical categories (complications & prognosis, diagnosis & clinical presentation, epidemiology, prevention & screening/monitoring, and treatment) and six specialties (cardiology, endocrinology, hematology-oncology, infectious disease, internal medicine, and neurology). A total of 265 disease-related questions were evaluated by pharmacist reviewers based on if an answer was found (yes, no), whether the answer …
Host Ip3r Channels Are Dispensable For Rotavirus Ca2+ Signaling But Critical For Intercellular Ca2+ Waves That Prime Uninfected Cells For Rapid Virus Spread, Kristen A Engevik, Jenna M Ellis, Joseph M Hyser
Host Ip3r Channels Are Dispensable For Rotavirus Ca2+ Signaling But Critical For Intercellular Ca2+ Waves That Prime Uninfected Cells For Rapid Virus Spread, Kristen A Engevik, Jenna M Ellis, Joseph M Hyser
Faculty, Staff and Students Publications
Many viruses exploit host Ca2+ signaling to facilitate their replication; however, little is known about how Ca2+ signals from different host and viral channels contribute to the overall dysregulation of Ca2+ signaling or promote virus replication. Using cells lacking IP3R, a host ER Ca2+ channel, we delineated intracellular Ca2+ signals within virus-infected cells and intercellular Ca2+ waves (ICWs), which increased Ca2+ signaling in neighboring, uninfected cells. In infected cells, IP3R was dispensable for rotavirus-induced Ca2+ signaling and replication, suggesting the rotavirus NSP4 viroporin supplies these signals. However, IP3R-mediated ICWs increase rotavirus replication kinetics and spread, indicating that the Ca2+ signals …
Novel Species Of Triatoma (Hemiptera: Reduviidae) Identified In A Case Of Vectorial Transmission Of Chagas Disease In Northern Belize, Silvia A Justi, Russell Manzanero, Emily Zielinski-Gutierrez, Claudia Herrera, Julie Thompson, Rajendra Mandage, Hans Desale, Adrianna Maliga, Kim Bautista, Shannon E Ronca, Francis Morey, Rafael Chacon Fuentes, Beatriz Lopez, Eric Dumonteil, Gerhaldine H Morazan, Kristy O Murray
Novel Species Of Triatoma (Hemiptera: Reduviidae) Identified In A Case Of Vectorial Transmission Of Chagas Disease In Northern Belize, Silvia A Justi, Russell Manzanero, Emily Zielinski-Gutierrez, Claudia Herrera, Julie Thompson, Rajendra Mandage, Hans Desale, Adrianna Maliga, Kim Bautista, Shannon E Ronca, Francis Morey, Rafael Chacon Fuentes, Beatriz Lopez, Eric Dumonteil, Gerhaldine H Morazan, Kristy O Murray
Faculty, Staff and Students Publications
Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel …
Knowledge, Attitudes, And Subjective Norms Associated With Covid-19 Vaccination Among Pregnant Women In Kenya: An Online Cross-Sectional Pilot Study Using Whatsapp, Sarah E Messiah
Faculty, Staff and Student Publications
COVID-19 vaccination during pregnancy has been recommended, but the perceptions related to uptake remain unexplored. This pilot study aimed to explore how perceptions influence COVID-19 vaccine uptake among a sample of 115 pregnant women in Kenya, recruited via WhatsApp. Data were collected using an adapted online questionnaire between May and October 2022. Logistic analyses assessed the relationship between COVID-19 vaccination uptake and the Theory of Reasoned Action (TRA) constructs: attitudes and subjective norms. COVID-19 vaccination coverage was 73%, with vaccine hesitancy estimated at 41.4% among the unvaccinated group. Most participants had completed college education and had good knowledge of COVID-19 …
Expanded T Lymphocytes In The Cerebrospinal Fluid Of Multiple Sclerosis Patients Are Specific For Epstein-Barr-Virus-Infected B Cells
Faculty, Staff and Student Publications
Epstein-Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the …