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Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi Sep 2023

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …


Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah Sep 2023

Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah

Faculty, Staff and Student Publications

No abstract provided.


Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou Sep 2023

Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and …


Epigenome-Wide Dna Methylation Association Study Of Circulating Ige Levels Identifies Novel Targets For Asthma, Kathryn Recto, Priyadarshini Kachroo, Tianxiao Huan, David Van Den Berg, Gha Young Lee, Helena Bui, Dong Heon Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Scott T Weiss, George T O'Connor, Daniel Levy, Dawn L Demeo Sep 2023

Epigenome-Wide Dna Methylation Association Study Of Circulating Ige Levels Identifies Novel Targets For Asthma, Kathryn Recto, Priyadarshini Kachroo, Tianxiao Huan, David Van Den Berg, Gha Young Lee, Helena Bui, Dong Heon Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Scott T Weiss, George T O'Connor, Daniel Levy, Dawn L Demeo

Faculty, Staff and Student Publications

BACKGROUND: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases.

METHODS: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs …


Multivariate Genetic Analysis Of Personality And Cognitive Traits Reveals Abundant Pleiotropy, Guy Hindley, Alexey A Shadrin, Dennis Van Der Meer, Nadine Parker, Weiqiu Cheng, Kevin S O'Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Børge Holen, Thomas Bjella, Ian J Deary, Gail Davies, W David Hill, Jan Bressler, Sudha Seshadri, Chun Chieh Fan, Torill Ueland, Srdjan Djurovic, Olav B Smeland, Oleksandr Frei, Anders M Dale, Ole A Andreassen Sep 2023

Multivariate Genetic Analysis Of Personality And Cognitive Traits Reveals Abundant Pleiotropy, Guy Hindley, Alexey A Shadrin, Dennis Van Der Meer, Nadine Parker, Weiqiu Cheng, Kevin S O'Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Børge Holen, Thomas Bjella, Ian J Deary, Gail Davies, W David Hill, Jan Bressler, Sudha Seshadri, Chun Chieh Fan, Torill Ueland, Srdjan Djurovic, Olav B Smeland, Oleksandr Frei, Anders M Dale, Ole A Andreassen

Faculty, Staff and Student Publications

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies …


An Unusual Case Of Acute Scrotal Pain, Thomas Damrow, Ryan Bellinger, Judy Lin, Jennifer A Walker Sep 2023

An Unusual Case Of Acute Scrotal Pain, Thomas Damrow, Ryan Bellinger, Judy Lin, Jennifer A Walker

Faculty, Staff and Student Publications

Patients frequently present to the emergency department with complaints of scrotal or testicular pain. Generally, there is an algorithmic approach to workup, which includes assessment for torsion, infection, or vascular causes, and musculoskeletal causes of pain are also sometimes considered. Spinal cord pathology, however, is less often explored as a cause of testicular pain. Here, we present a case of a 45-year-old man with end-stage renal disease and hypertension who presented with acute testicular pain. After a comprehensive workup, however, the source of pain was not initially found. Progression of the patient's symptoms led to the diagnosis of spontaneous spinal …


Tepotinib Treatment In Patients With Met Exon 14-Skipping Non-Small Cell Lung Cancer: Long-Term Follow-Up Of The Vision Phase 2 Nonrandomized Clinical Trial, Julien Mazieres, Paul K Paik, Marina C Garassino, Xiuning Le, Hiroshi Sakai, Remi Veillon, Egbert F Smit, Alexis B Cortot, Jo Raskin, Santiago Viteri, Yi-Long Wu, James C H Yang, Myung-Ju Ahn, Rui Ma, Jun Zhao, Aurora O'Brate, Karin Berghoff, Rolf Bruns, Gordon Otto, Andreas Johne, Enriqueta Felip, Michael Thomas Sep 2023

Tepotinib Treatment In Patients With Met Exon 14-Skipping Non-Small Cell Lung Cancer: Long-Term Follow-Up Of The Vision Phase 2 Nonrandomized Clinical Trial, Julien Mazieres, Paul K Paik, Marina C Garassino, Xiuning Le, Hiroshi Sakai, Remi Veillon, Egbert F Smit, Alexis B Cortot, Jo Raskin, Santiago Viteri, Yi-Long Wu, James C H Yang, Myung-Ju Ahn, Rui Ma, Jun Zhao, Aurora O'Brate, Karin Berghoff, Rolf Bruns, Gordon Otto, Andreas Johne, Enriqueta Felip, Michael Thomas

Faculty, Staff and Student Publications

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, setting, and participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 …


Microfluidic Paper-Based Device Coupled With 3d Printed Imaging Box For Colorimetric Detection In Resource-Limited Settings, Vijay Vaishampayan, Oinam Robita Chanu, Balasubramanian Sivasamy, Muthamilselvi Ponnuchamy, Varshini Karthik, Ambar Pendharkar, Lohith Srinivas Thotakura, Aryan Prabhu, Venkatesan Dhananjeyan, Ashish Kapoor Sep 2023

Microfluidic Paper-Based Device Coupled With 3d Printed Imaging Box For Colorimetric Detection In Resource-Limited Settings, Vijay Vaishampayan, Oinam Robita Chanu, Balasubramanian Sivasamy, Muthamilselvi Ponnuchamy, Varshini Karthik, Ambar Pendharkar, Lohith Srinivas Thotakura, Aryan Prabhu, Venkatesan Dhananjeyan, Ashish Kapoor

Faculty, Staff and Student Publications

Rapid and effective methods for the detection of analytes such as water contaminants, food adulterants and biomolecules are essential for the protection of public health and environmental protection. Most of the currently established analytical techniques need sophisticated equipment, centralized testing facilities, costly operations, and trained personnel. Such limitations make them inaccessible to the general populace, particularly in regions with limited resources. The emergence of microfluidic devices offers a promising alternative to overcome several such constraints. This work describes a protocol for fabricating a low-cost, open-source paper-based microfluidic device using easily available tools and materials for colorimetric detection of analytes. The …


Identifying Brain Hierarchical Structures Associated With Alzheimer’S Disease Using A Regularized Regression Method With Tree Predictors, Yi Zhao, Bingkai Wang, Chin-Fu Liu, Andreia V Faria, Michael I Miller, Brian S Caffo, Xi Luo Sep 2023

Identifying Brain Hierarchical Structures Associated With Alzheimer’S Disease Using A Regularized Regression Method With Tree Predictors, Yi Zhao, Bingkai Wang, Chin-Fu Liu, Andreia V Faria, Michael I Miller, Brian S Caffo, Xi Luo

Faculty, Staff and Student Publications

Brain segmentation at different levels is generally represented as hierarchical trees. Brain regional atrophy at specific levels was found to be marginally associated with Alzheimer's disease outcomes. In this study, we propose an ℓ1 -type regularization for predictors that follow a hierarchical tree structure. Considering a tree as a directed acyclic graph, we interpret the model parameters from a path analysis perspective. Under this concept, the proposed penalty regulates the total effect of each predictor on the outcome. With regularity conditions, it is shown that under the proposed regularization, the estimator of the model coefficient is consistent in ℓ2 -norm …


Examining Readiness For Implementing Practice Changes In Federally Qualified Health Centers: A Rapid Qualitative Study, Emanuelle M Dias, Timothy J Walker, Derek W Craig, Robert Gibson, Jacob Szeszulski, Heather M Brandt, Hiluv Johnson, Andrea Lamont, Abraham Wandersman, Maria E Fernandez Sep 2023

Examining Readiness For Implementing Practice Changes In Federally Qualified Health Centers: A Rapid Qualitative Study, Emanuelle M Dias, Timothy J Walker, Derek W Craig, Robert Gibson, Jacob Szeszulski, Heather M Brandt, Hiluv Johnson, Andrea Lamont, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

Implementing evidence-based interventions remains slow in federally qualified health centers (FQHCs). The purpose of this study is to qualitatively examine the R = MC2 (Readiness = motivation × innovation specific capacity × general capacity) heuristic subcomponents in the context of implementing general and colorectal cancer screening (CRCS)-related practice changes in FQHCs. We conducted 17 interviews with FQHC employees to examine (1) experiences with successful or unsuccessful practice change efforts, (2) using approaches to promote CRCS, and (3) opinions about R = MC2 subcomponents. We conducted a rapid qualitative analysis to examine the frequency, depth, and spontaneity of subcomponents. Priority, compatibility, …


Significant Improvement Of Fidelity For Encoded Quantum Bell Pairs At Long And Short-Distance Communication Along With Generalized Circuit, Syed Emad Uddin Shubha, Md Saifur Rahman, M R C Mahdy Sep 2023

Significant Improvement Of Fidelity For Encoded Quantum Bell Pairs At Long And Short-Distance Communication Along With Generalized Circuit, Syed Emad Uddin Shubha, Md Saifur Rahman, M R C Mahdy

Faculty, Staff and Student Publications

Quantum entanglement is a unique criterion of the quantum realm and an essential tool to secure quantum communication. Ensuring high-fidelity entanglement has always been a challenging task owing to interaction with the hostile channel environment created due to quantum noise and decoherence. Though several methods have been proposed, correcting almost all arbitrary errors is still a gigantic task. As one of the main contributions of this work, a new model for 'large distance communication' has been proposed, which may correct all bit flip errors or other errors quite extensively if proper encoding and subspace measurements are used. To achieve this …


Medical Students' Attitudes And Beliefs Toward Psilocybin: Does Terminology And Personal Experience With Psychedelics Matter?, Antonio F Pagán, Claudia Lex, Jair C Soares, Thomas D Meyer Sep 2023

Medical Students' Attitudes And Beliefs Toward Psilocybin: Does Terminology And Personal Experience With Psychedelics Matter?, Antonio F Pagán, Claudia Lex, Jair C Soares, Thomas D Meyer

Faculty, Staff and Student Publications

BACKGROUND: Psilocybin and psychedelic-assisted therapy (PAT) have gained renewed interest due to recent findings that PAT can enhance therapeutic outcomes. In 2019, the U.S. Food & Drug Administration (FDA) approved breakthrough therapy status to psilocybin for the treatment of depression, but PAT has yet to be approved as a therapeutic treatment for mental health disorders. Should the FDA approve PAT, medical students will serve as gatekeepers to PAT.

METHODS: Medical students (

RESULTS: Regardless of the terminology utilized, medical students held overall positive attitudes but their attitudes were significantly more positive when the term "psilocybin" was used. Furthermore, experience with …


Innate Immune Activation And White Matter Injury In A Rat Model Of Neonatal Intraventricular Hemorrhage Are Dependent On Developmental Stage, Miriam Zamorano, Scott D Olson, Candice Haase, Juan J Herrera, Shuning Huang, David J Sequeira, Charles S Cox, Brandon A Miller Sep 2023

Innate Immune Activation And White Matter Injury In A Rat Model Of Neonatal Intraventricular Hemorrhage Are Dependent On Developmental Stage, Miriam Zamorano, Scott D Olson, Candice Haase, Juan J Herrera, Shuning Huang, David J Sequeira, Charles S Cox, Brandon A Miller

Faculty, Staff and Student Publications

Background: Inflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during the time which IVH occurs and its consequences develop. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model have not been examined. Understanding how the timing of IVH affects outcome may provide important insights into both IVH pathophysiology and innate immune development.

Methods: We used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. …


Implant Survival In Tissue-Engineered Mandibular Reconstruction-Early Experiences, Victoria A Mañón, Nicholas Oda, Emeric Boudreaux, Huy Tran, Simon Young, James C Melville Sep 2023

Implant Survival In Tissue-Engineered Mandibular Reconstruction-Early Experiences, Victoria A Mañón, Nicholas Oda, Emeric Boudreaux, Huy Tran, Simon Young, James C Melville

Faculty, Staff and Student Publications

Study design: This article is to evaluate the early outcomes of dental implants placed in bone generated with tissueengineering techniques, specifically recombinant human bone morphogenic protein-2 (rhBMP-2), allogeneicbone particulate, and bone marrow aspirate concentrate (BMAC) in patients with resection of benignpathology.

Objective: To evaluate the long-term prognosis of dental implants placed in tissue engineered mandibular reconstruction.

Methods: We retrospectively evaluated 12 patient records, all of whom underwent segmental mandibular resection of benign pathology and reconstruction with a combination of BMAC, rhBMP-2, and allogeneic bone. Collecteddata points included the patient's age, gender, medical and social histories, implant site and placement date, …


Dependence Motives And Use Contexts That Predicted Smoking Cessation And Vaping Cessation: A Two-Year Longitudinal Study With 13 Waves, Joon Kyung Nam, Megan E Piper, Zhaoxue Tong, Runze Li, James J Yang, Douglas E Jorenby, Anne Buu Sep 2023

Dependence Motives And Use Contexts That Predicted Smoking Cessation And Vaping Cessation: A Two-Year Longitudinal Study With 13 Waves, Joon Kyung Nam, Megan E Piper, Zhaoxue Tong, Runze Li, James J Yang, Douglas E Jorenby, Anne Buu

Faculty, Staff and Student Publications

INTRODUCTION: Prior studies examining the impact of e-cigarette use, dependence, cessation motivation/goals, and environmental restriction on smoking cessation were based on cross-sectional or shorter-term longitudinal data with binary outcomes. There is also a critical knowledge gap in corresponding impact on vaping cessation. This study aims to fill in these gaps by investigating these factors' effects on speed of progression to smoking and vaping cessation.

METHODS: This study conducted secondary analysis of data from 13 waves of assessment of adult cigarette users in Wisconsin from October 2015 through July 2019. Cox regression was employed to examine baseline predictors' effects on speed …


Patient Shielding During Dentomaxillofacial Radiography: Recommendations From The American Academy Of Oral And Maxillofacial Radiology, Erika Benavides, Avni Bhula, Anita Gohel, Alan G Lurie, Sanjay M Mallya, Aruna Ramesh, Donald A Tyndall Sep 2023

Patient Shielding During Dentomaxillofacial Radiography: Recommendations From The American Academy Of Oral And Maxillofacial Radiology, Erika Benavides, Avni Bhula, Anita Gohel, Alan G Lurie, Sanjay M Mallya, Aruna Ramesh, Donald A Tyndall

Faculty, Staff and Student Publications

BACKGROUND: The American Academy of Oral and Maxillofacial Radiology established an ad hoc committee to draft evidence-based recommendations and clinical guidance for the application of patient contact shielding during dentomaxillofacial imaging.

TYPES OF STUDIES REVIEWED: The committee reviewed monographs and reports from radiation protection organizations and studies that reported radiation dose to gonads, breasts, and thyroid gland from dentomaxillofacial imaging.

RESULTS: Considering the absence of radiation-induced heritable effects in humans and the negligible dose to the gonads and fetus from dentomaxillofacial imaging, the committee recommends discontinuing shielding of the gonads, pelvic structures, and fetuses during all dentomaxillofacial radiographic imaging procedures. …


The Burden Of Antimicrobial Resistance In The Americas In 2019: A Cross-Country Systematic Analysis, Antimicrobial Resistance Collaborators Sep 2023

The Burden Of Antimicrobial Resistance In The Americas In 2019: A Cross-Country Systematic Analysis, Antimicrobial Resistance Collaborators

Faculty, Staff and Student Publications

BACKGROUND: Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive-despite the region's long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat.

METHODS: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature …


Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu Sep 2023

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …


Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green Sep 2023

Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green

Faculty, Staff and Student Publications

The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.


Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres Sep 2023

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …


Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylatio, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler Sep 2023

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylatio, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …


Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons Sep 2023

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …


Brain Imaging With Portable Low-Field Mri, W Taylor Kimberly, Annabel J Sorby-Adams, Andrew G Webb, Ed X Wu, Rachel Beekman, Ritvij Bowry, Steven J Schiff, Adam De Havenon, Francis X Shen, Gordon Sze, Pamela Schaefer, Juan Eugenio Iglesias, Matthew S Rosen, Kevin N Sheth Sep 2023

Brain Imaging With Portable Low-Field Mri, W Taylor Kimberly, Annabel J Sorby-Adams, Andrew G Webb, Ed X Wu, Rachel Beekman, Ritvij Bowry, Steven J Schiff, Adam De Havenon, Francis X Shen, Gordon Sze, Pamela Schaefer, Juan Eugenio Iglesias, Matthew S Rosen, Kevin N Sheth

Faculty, Staff and Student Publications

The advent of portable, low-field MRI (LF-MRI) heralds new opportunities in neuroimaging. Low power requirements and transportability have enabled scanning outside the controlled environment of a conventional MRI suite, enhancing access to neuroimaging for indications that are not well suited to existing technologies. Maximizing the information extracted from the reduced signal-to-noise ratio of LF-MRI is crucial to developing clinically useful diagnostic images. Progress in electromagnetic noise cancellation and machine learning reconstruction algorithms from sparse k-space data as well as new approaches to image enhancement have now enabled these advancements. Coupling technological innovation with bedside imaging creates new prospects in …


False-Positive Early Indium-111 Leukocyte Scan, F Lomena, R Abello, A Garcia, C Piera, R Herranz, J Pavia, J Setoain Sep 2023

False-Positive Early Indium-111 Leukocyte Scan, F Lomena, R Abello, A Garcia, C Piera, R Herranz, J Pavia, J Setoain

Faculty, Staff and Student Publications

Introduction

We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

Methods

CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatographymass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

Results

The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. …


A Pilot Study Evaluating The Role Of Ivabradine For Rate Control In Patients With Rheumatic Atrial Fibrillation, Arpita Katheria, Aditya Kapoor, Ankit Sahu, Kamlesh Raut, Harshit Khare, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari Sep 2023

A Pilot Study Evaluating The Role Of Ivabradine For Rate Control In Patients With Rheumatic Atrial Fibrillation, Arpita Katheria, Aditya Kapoor, Ankit Sahu, Kamlesh Raut, Harshit Khare, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

OBJECTIVES: Ivabradine may have a role in rate control of atrial fibrillation (AF) due to effects on HCN channels in AV node. We studied role of Ivabradine in rate control of rheumatic AF.

METHODS: 80 patients, rheumatic AF, HR > 100 bpm (age 47 ± 11 yrs, AF duration 6.8 ± 2.9 years, rate 131 ± 16 bpm) on maximally tolerated ββ or CCB's, randomized to Ivabradine or escalated ββ/CCB. Ivabradine started @ 2.5 mg BD; increased to 5 mg BD if inadequate response at 1 week (failure to decrease HR < 10% vs baseline). After Holter at 1 month, dose escalated to 7.5 mg BD if needed.

RESULTS: Ivabradine resulted in significantly lower HR (81 ± 10 …


Patient-Reported Outcomes In Older Breast Cancer Survivors With And Without Prior Chemotherapy Treatment, Taiwo Adesoye, Kai-Ping Liao, Susan Peterson, Liang Li, Daria Zorzi, Holly M Holmes, Mariana Chavez-Macgregor, Sharon H Giordano Sep 2023

Patient-Reported Outcomes In Older Breast Cancer Survivors With And Without Prior Chemotherapy Treatment, Taiwo Adesoye, Kai-Ping Liao, Susan Peterson, Liang Li, Daria Zorzi, Holly M Holmes, Mariana Chavez-Macgregor, Sharon H Giordano

Faculty, Staff and Student Publications

BACKGROUND: Little is known about long-term treatment-related symptoms in older breast cancer survivors. We characterized long-term patient-reported symptoms and examined factors associated with the presence and severity of symptoms, and symptom interference with daily activities.

METHODS: Texas Cancer Registry (TCR) Medicare linkage data was used to identify breast cancer patients age 65 and older with local/regional stage disease diagnosed between 2012-2013. Symptom burden was assessed using breast-specific items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). Demographic and clinical data also were collected. Logistic regression models were used to assess the association between symptom …


Cancer Patients' Preferences And Perceptions Of Advantages And Disadvantages Of Telehealth Visits During The Covid-19 Pandemic, Deepika Kumar, Nancy Gordon, Constanza Zamani, Tammy Sheehan, Ernesto Martin, Olga Egorova, Jessica Payne, Tatjana Kolevska, Elad Neeman, Raymond Liu Sep 2023

Cancer Patients' Preferences And Perceptions Of Advantages And Disadvantages Of Telehealth Visits During The Covid-19 Pandemic, Deepika Kumar, Nancy Gordon, Constanza Zamani, Tammy Sheehan, Ernesto Martin, Olga Egorova, Jessica Payne, Tatjana Kolevska, Elad Neeman, Raymond Liu

Faculty, Staff and Student Publications

PURPOSE: We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters.

METHODS: We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use.

RESULTS: The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated …


Cellular And Metabolic Characteristics Of Pre-Leukemic Hematopoietic Progenitors With Gata2 Haploinsufficiency, Avigail Rein, Ifat Geron, Eitan Kugler, Hila Fishman, Eyal Gottlieb, Ifat Abramovich, Amir Giladi, Ido Amit, Roger Mulet-Lazaro, Ruud Delwel, Stefan Gröschel, Smadar Levin-Zaidman, Nili Dezorella, Vered Holdengreber, Tata Nageswara Rao, Joanne Yacobovich, Orna Steinberg-Shemer, Qiu-Hua Huang, Yun Tan, Sai-Juan Chen, Shai Izraeli, Yehudit Birger Sep 2023

Cellular And Metabolic Characteristics Of Pre-Leukemic Hematopoietic Progenitors With Gata2 Haploinsufficiency, Avigail Rein, Ifat Geron, Eitan Kugler, Hila Fishman, Eyal Gottlieb, Ifat Abramovich, Amir Giladi, Ido Amit, Roger Mulet-Lazaro, Ruud Delwel, Stefan Gröschel, Smadar Levin-Zaidman, Nili Dezorella, Vered Holdengreber, Tata Nageswara Rao, Joanne Yacobovich, Orna Steinberg-Shemer, Qiu-Hua Huang, Yun Tan, Sai-Juan Chen, Shai Izraeli, Yehudit Birger

Faculty, Staff and Student Publications

Mono-allelic germline disruptions of the transcription factor GATA2 result in a propensity for developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), affecting more than 85% of carriers. How a partial loss of GATA2 functionality enables leukemic transformation years later is unclear. This question has remained unsolved mainly due to the lack of informative models, as Gata2 heterozygote mice do not develop hematologic malignancies. Here we show that two different germline Gata2 mutations (TgErg/Gata2het and TgErg/Gata2L359V) accelerate AML in mice expressing the human hematopoietic stem cell regulator ERG. Analysis of Erg/Gata2het fetal liver and bone marrow-derived hematopoietic cells revealed a …


Use Of Compartmental Modeling And Retinol Isotope Dilution To Determine Vitamin A Stores In Young People With Sickle Cell Disease Before And After Vitamin A Supplementation, Jennifer Lynn Ford, Michael H Green, Jefferson N Brownell, Joanne Balmer Green, Anthony Oxley, Georg Lietz, Joan I Schall, Virginia A Stallings Sep 2023

Use Of Compartmental Modeling And Retinol Isotope Dilution To Determine Vitamin A Stores In Young People With Sickle Cell Disease Before And After Vitamin A Supplementation, Jennifer Lynn Ford, Michael H Green, Jefferson N Brownell, Joanne Balmer Green, Anthony Oxley, Georg Lietz, Joan I Schall, Virginia A Stallings

Faculty, Staff and Student Publications

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD.

OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects.

METHODS: Composite plasma [

RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 μmol, equivalent to ∼11 mo of stored vitamin …


Clinicopathologic Analysis Of Covid-19 Associated Thrombi In The Setting Of Large Vessel Occlusion: A Prospective Case-Control Study, Faheem Sheriff, Jonathan Lavezo, Ryan Floresca, Mohammad Rauf Chaudhury, Gabriela Colina, Robert Regenhardt, Vikas Gupta, Gustavo Rodriguez, Alberto Maud Sep 2023

Clinicopathologic Analysis Of Covid-19 Associated Thrombi In The Setting Of Large Vessel Occlusion: A Prospective Case-Control Study, Faheem Sheriff, Jonathan Lavezo, Ryan Floresca, Mohammad Rauf Chaudhury, Gabriela Colina, Robert Regenhardt, Vikas Gupta, Gustavo Rodriguez, Alberto Maud

Faculty, Staff and Student Publications

Background: Acute ischemic stroke secondary to large vessel occlusion is among the most serious complications associated with COVID-19 infection resulting in worse morbidity and mortality. We sought to study the association between COVID-19 infection and large vessel occlusion thrombus pathology to better define the etiopathogenesis of this atypical cause of stroke.

Methods: Thrombi were collected during mechanical thrombectomy and stained using hematoxylin and eosin. Blinded analysis of pathology was prospectively performed by a board-certified neuropathologist. Red blood cell, fibrin, and white blood cell predominance was ascertained. Concomitant peripheral blood counts and clinical and imaging data were collected and analyzed. All …