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Expanding Treatment For Opioid Use Disorder In Publicly Funded Primary Care Clinics: Exploratory Evaluation Of The Nyc Health + Hospitals Buprenorphine Echo Program, Babak Tofighi, Noah Isaacs, Hannah Byrnes-Enoch, Rebecca Lakew, Joshua D Lee, Carolyn Berry, Daniel Schatz Nov 2019

Expanding Treatment For Opioid Use Disorder In Publicly Funded Primary Care Clinics: Exploratory Evaluation Of The Nyc Health + Hospitals Buprenorphine Echo Program, Babak Tofighi, Noah Isaacs, Hannah Byrnes-Enoch, Rebecca Lakew, Joshua D Lee, Carolyn Berry, Daniel Schatz

Project ECHO Bibliography

Project Extension for Community Healthcare Outcomes (Project ECHO) offers an innovative and low-cost approach to enhancing the management of complex conditions among primary care providers. The NYC Health + Hospitals Buprenorphine ECHO (H + H ECHO) program offers primary care providers (PCPs) training and support in managing opioid use disorder (OUD). This exploratory study assessed the feasibility of a 16-session video conferencing platform led by Addiction Medicine experts in improving addiction knowledge, perceived self-efficacy, and buprenorphine prescribing among PCPs located in 17 publicly-funded ambulatory care clinics. A pre- and post-training survey assessed changes in knowledge and self-efficacy. Buprenorphine prescribing patterns …


Precision Medicine In Pancreatic Disease-Knowledge Gaps And Research Opportunities: Summary Of A National Institute Of Diabetes And Digestive And Kidney Diseases Workshop., Mark E Lowe, Dana K Andersen, Richard M Caprioli, Jyoti Choudhary, Zobeida Cruz-Monserrate, Anil K Dasyam, Christopher E Forsmark, Fred S Gorelick, Joe W Gray, Mark Haupt, Kimberly A Kelly, Kenneth P Olive, Sylvia K Plevritis, Noa Rappaport, Holger R Roth, Hanno Steen, S Joshua Swamidass, Temel Tirkes, Aliye Uc, Kirill Veselkov, David C Whitcomb, Aida Habtezion Nov 2019

Precision Medicine In Pancreatic Disease-Knowledge Gaps And Research Opportunities: Summary Of A National Institute Of Diabetes And Digestive And Kidney Diseases Workshop., Mark E Lowe, Dana K Andersen, Richard M Caprioli, Jyoti Choudhary, Zobeida Cruz-Monserrate, Anil K Dasyam, Christopher E Forsmark, Fred S Gorelick, Joe W Gray, Mark Haupt, Kimberly A Kelly, Kenneth P Olive, Sylvia K Plevritis, Noa Rappaport, Holger R Roth, Hanno Steen, S Joshua Swamidass, Temel Tirkes, Aliye Uc, Kirill Veselkov, David C Whitcomb, Aida Habtezion

Articles, Abstracts, and Reports

A workshop on research gaps and opportunities for Precision Medicine in Pancreatic Disease was sponsored by the National Institute of Diabetes and Digestive Kidney Diseases on July 24, 2019, in Pittsburgh. The workshop included an overview lecture on precision medicine in cancer and 4 sessions: (1) general considerations for the application of bioinformatics and artificial intelligence; (2) omics, the combination of risk factors and biomarkers; (3) precision imaging; and (4) gaps, barriers, and needs to move from precision to personalized medicine for pancreatic disease. Current precision medicine approaches and tools were reviewed, and participants identified knowledge gaps and research needs …


A Rare Site Of Spread Of A Common Cancer, Sameen Khalid, Graziella Paniz, Aamer Abbass, Edgar Fischer, Gulshan Parasher, Denis Mccarthy Nov 2019

A Rare Site Of Spread Of A Common Cancer, Sameen Khalid, Graziella Paniz, Aamer Abbass, Edgar Fischer, Gulshan Parasher, Denis Mccarthy

Pathology Research and Scholarship

Breast cancer is the most commonly diagnosed malignancy affecting women worldwide with estimated 252,710 new cases of invasive breast cancer in women in the USA in 2017. It is the second most prevalent cause of cancer-related death after lung cancer in females with an expected annual mortality rate of 16% [1]. Promotion of public awareness, screening programs, early diagnosis, intensive local treat- ment, and changes in chemotherapy regimens with endo- crine and targeted therapy account for a notable decrease in mortality. Nevertheless, these measures do not seem to have impacted the prognosis in patients with distant metastasis. Breast cancer has …


Svtools: Population-Scale Analysis Of Structural Variation, David E Larson, Haley J Abel, Colby Chiang, Abhijit Badve, Indraniel Das, James M Eldred, Ryan M Layer, Ira M Hall Nov 2019

Svtools: Population-Scale Analysis Of Structural Variation, David E Larson, Haley J Abel, Colby Chiang, Abhijit Badve, Indraniel Das, James M Eldred, Ryan M Layer, Ira M Hall

Open Access Publications

SUMMARY: Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps-including deletions, duplications, mobile element insertions, inversions and other rearrangements-in many thousands of human genomes. We show that this pipeline …


Incorporating B Cell Activating Factor (Baff) Into The Membrane Of Rabies Virus (Rabv) Particles Improves The Speed And Magnitude Of Vaccine-Induced Antibody Responses., Joseph R Plummer, James P Mcgettigan Nov 2019

Incorporating B Cell Activating Factor (Baff) Into The Membrane Of Rabies Virus (Rabv) Particles Improves The Speed And Magnitude Of Vaccine-Induced Antibody Responses., Joseph R Plummer, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that links innate with adaptive immunity. BAFF signals through receptors on B cells, making it an attractive molecule to potentiate vaccine-induced B cell responses. We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses. To test this hypothesis, we constructed a recombinant RABV-based vector expressing virus membrane-anchored murine BAFF (RABV-ED51-mBAFF). BAFF was incorporated into the RABV particle and determined to …


Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein Nov 2019

Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein

2010-2019 OA Pubs

No abstract provided.


Pharmacokinetics Of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules In De Novo Liver Transplant, Derek A Dubay, Lewis Teperman, Kimi Ueda, Andrew Silverman, William Chapman, Angel E Alsina, Carmelina Tyler, Daniel R Stevens Nov 2019

Pharmacokinetics Of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules In De Novo Liver Transplant, Derek A Dubay, Lewis Teperman, Kimi Ueda, Andrew Silverman, William Chapman, Angel E Alsina, Carmelina Tyler, Daniel R Stevens

2010-2019 OA Pubs

The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0.13 mg/kg/day (taken once daily; n = 29) or twice-daily immediate-release tacrolimus capsules (IR-Tac) at 0.10-0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5-15 ng/mL thereafter. Twenty-four-hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year …


Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha Nov 2019

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …


Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal Nov 2019

Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal

Manuscripts, Articles, Book Chapters and Other Papers

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = …


Sirna Targeting And Treatment Of Gastrointestinal Diseases., Rachel Chevalier Nov 2019

Sirna Targeting And Treatment Of Gastrointestinal Diseases., Rachel Chevalier

Manuscripts, Articles, Book Chapters and Other Papers

RNA interference via small interfering RNA (siRNA) offers opportunities to precisely target genes that contribute to gastrointestinal (GI) pathologies, such as inflammatory bowel disease, celiac, and esophageal scarring. Delivering the siRNA to the GI tract proves challenging as the harsh environment of the intestines degrades the siRNA before it can reach its target or blocks its entry into its site of action in the cytoplasm. Additionally, the GI tract is large and disease is often localized to a specific site. This review discusses polymer and lipid-based delivery systems for protection and targeting of siRNA therapies to the GI tract to …


From Suffrage To The Senate: Expanding Inclusion In Women's Rights To Achieve Women's Health Equality., Frances Grimstad Nov 2019

From Suffrage To The Senate: Expanding Inclusion In Women's Rights To Achieve Women's Health Equality., Frances Grimstad

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Enhancing Clinical Concept Extraction With Contextual Embeddings, Yuqi Si, Jingqi Wang, Hua Xu, Kirk Roberts Nov 2019

Enhancing Clinical Concept Extraction With Contextual Embeddings, Yuqi Si, Jingqi Wang, Hua Xu, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Neural network-based representations ("embeddings") have dramatically advanced natural language processing (NLP) tasks, including clinical NLP tasks such as concept extraction. Recently, however, more advanced embedding methods and representations (eg, ELMo, BERT) have further pushed the state of the art in NLP, yet there are no common best practices for how to integrate these representations into clinical tasks. The purpose of this study, then, is to explore the space of possible options in utilizing these new models for clinical concept extraction, including comparing these to traditional word embedding methods (word2vec, GloVe, fastText).

MATERIALS AND METHODS: Both off-the-shelf, open-domain embeddings and …


Development And Psychometric Properties Of A Prostate Cancer Knowledge Scale For African American Men, Otis L. Owens, Abbas Tavakoli Drph, Theda Rose, Nikki R. Wooten Nov 2019

Development And Psychometric Properties Of A Prostate Cancer Knowledge Scale For African American Men, Otis L. Owens, Abbas Tavakoli Drph, Theda Rose, Nikki R. Wooten

Faculty Publications

African American men have the highest prostate cancer-related mortality nationally. In response to this disparity, targeted interventions are emerging to enhance African American men's prostate cancer (PrCA) knowledge to ensure they are equipped to make informed decisions about PrCA screening with health-care providers. African American men's PrCA knowledge has been measured inconsistently over time with limited psychometric evidence. The factor structure of this construct in African American men is relatively unknown. This study describes the development and psychometric evaluation of an 18-item Prostate Cancer Knowledge Scale among 352 African American men. Exploratory factor analysis (EFA) was conducted using weighted least …


Exposures At Day Labor Corners: Using Existing Georeferenced Data To Describe Features Of Urban Environments, Maria Eugenia Fernández-Esquer, Amy E Hughes, Sandi L Pruitt Nov 2019

Exposures At Day Labor Corners: Using Existing Georeferenced Data To Describe Features Of Urban Environments, Maria Eugenia Fernández-Esquer, Amy E Hughes, Sandi L Pruitt

Faculty, Staff and Student Publications

PURPOSE: Latino day laborers are male immigrants from mainly Mexico and Central America who congregate at corners, that is, informal hiring sites, to solicit short-term employment. Studies describing the occupational environment of Latino day laborers traditionally measure jobsite exposures, not corner exposures. We sought to elucidate exposures at corners by describing their demographic, socioeconomic, occupational, business, built, and physical environmental characteristics and by comparing corner characteristics with other locations in a large urban county in Texas.

METHODS: We used multiple publicly available data sets from the U.S. Census, local tax authority, Google's Nearby Places Application Programming Interface, and Environmental Protection …


30-Day Emergency Department Revisit Rates Among Older Adults With Documented Dementia, Tyler Kent, Adriane Lesser, Juhi Israni, Ula Hwang, Christopher Carpenter, Kelly J Ko Nov 2019

30-Day Emergency Department Revisit Rates Among Older Adults With Documented Dementia, Tyler Kent, Adriane Lesser, Juhi Israni, Ula Hwang, Christopher Carpenter, Kelly J Ko

Open Access Publications

OBJECTIVES: Published literature on national emergency department (ED) revisit rates among older adults with dementia is sparse, despite anecdotal evidence of higher ED utilization. Thus we evaluated the odds ratio (OR) of 30-day ED revisits among older adults with dementia using a nationally representative sample.

DESIGN: We assessed the frequency of claims associated with a 30-day ED revisit among Medicare beneficiaries with and without a dementia diagnosis before or at index ED visit. We used a logistic regression model controlling for dementia, age, sex, race, region, Medicaid status, transfer to a skilled nursing facility after ED, primary care physician use …


Dc-Script Deficiency Delays Mouse Mammary Gland Development And Branching Morphogenesis, Chunling Tang, Renske J E Van Den Bijgaart, Maaike W G Looman, Nina Tel-Karthaus, Annemarie M A De Graaf, Susan Gilfillan, Marco Colonna, Marleen Ansems, Gosse J Adema Nov 2019

Dc-Script Deficiency Delays Mouse Mammary Gland Development And Branching Morphogenesis, Chunling Tang, Renske J E Van Den Bijgaart, Maaike W G Looman, Nina Tel-Karthaus, Annemarie M A De Graaf, Susan Gilfillan, Marco Colonna, Marleen Ansems, Gosse J Adema

Open Access Publications

Mammary glands are unique organs in which major adaptive changes occur in morphogenesis and development after birth. Breast cancer is the most common cancer and a major cause of mortality in females worldwide. We have previously identified the loss of expression of the transcription regulator DC-SCRIPT (Zfp366) as a prominent prognostic event in estrogen receptor positive breast cancer patients. DC-SCRIPT affects multiple transcriptional events in breast cancer cells, including estrogen and progesterone receptor-mediated transcription, and promotes CDKN2B-related cell cycle arrest. As loss of DC-SCRIPT expression appears an early event in breast cancer development, we here investigated the role of DC-SCRIPT …


Gene Expression Analysis To Detect Disseminated Tumor Cells In The Bone Marrow Of Triple-Negative Breast Cancer Patients Predicts Metastatic Relapse, Chidananda M Siddappa, Sreeraj G Pillai, Jackie Snider, Patsy Alldredge, Kathyrn Trinkaus, Mark A Watson, Rebecca Aft Nov 2019

Gene Expression Analysis To Detect Disseminated Tumor Cells In The Bone Marrow Of Triple-Negative Breast Cancer Patients Predicts Metastatic Relapse, Chidananda M Siddappa, Sreeraj G Pillai, Jackie Snider, Patsy Alldredge, Kathyrn Trinkaus, Mark A Watson, Rebecca Aft

Open Access Publications

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse.

METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM …


Tfeb Activation In Macrophages Attenuates Postmyocardial Infarction Ventricular Dysfunction Independently Of Atg5-Mediated Autophagy, Ali Javaheri, Geetika Bajpai, Antonino Picataggi, Smrithi Mani, Layla Foroughi, Hosannah Evie, Attila Kovacs, Carla J Weinheimer, Krzystztof Hyrc, Qingli Xiao, Andrea Ballabio, Jin-Moo Lee, Scot J Matkovich, Babak Razani, Joel D Schilling, Kory J Lavine, Abhinav Diwan Nov 2019

Tfeb Activation In Macrophages Attenuates Postmyocardial Infarction Ventricular Dysfunction Independently Of Atg5-Mediated Autophagy, Ali Javaheri, Geetika Bajpai, Antonino Picataggi, Smrithi Mani, Layla Foroughi, Hosannah Evie, Attila Kovacs, Carla J Weinheimer, Krzystztof Hyrc, Qingli Xiao, Andrea Ballabio, Jin-Moo Lee, Scot J Matkovich, Babak Razani, Joel D Schilling, Kory J Lavine, Abhinav Diwan

Open Access Publications

Lysosomes are at the epicenter of cellular processes critical for inflammasome activation in macrophages. Inflammasome activation and IL-1β secretion are implicated in myocardial infarction (MI) and resultant heart failure; however, little is known about how macrophage lysosomes regulate these processes. In mice subjected to cardiac ischemia/reperfusion (IR) injury and humans with ischemic cardiomyopathy, we observed evidence of lysosomal impairment in macrophages. Inducible macrophage-specific overexpression of transcription factor EB (TFEB), a master regulator of lysosome biogenesis (Mϕ-TFEB), attenuated postinfarction remodeling, decreased abundance of proinflammatory macrophages, and reduced levels of myocardial IL-1β compared with controls. Surprisingly, neither inflammasome suppression nor Mϕ-TFEB-mediated attenuation …


Genome-Wide Analysis Of Heterogeneous Nuclear Ribonucleoprotein (Hnrnp) Binding To Hiv-1 Rna Reveals A Key Role For Hnrnp H1 In Alternative Viral Mrna Splicing, Sebla B Kutluay, Ann Emery, Srinivasa R Penumutchu, Dana Townsend, Kasyap Tenneti, Michaela K Madison, Amanda M Stukenbroeker, Chelsea Powell, David Jannain, Blanton S Tolbert, Ronald I Swanstrom, Paul D Bieniasz Nov 2019

Genome-Wide Analysis Of Heterogeneous Nuclear Ribonucleoprotein (Hnrnp) Binding To Hiv-1 Rna Reveals A Key Role For Hnrnp H1 In Alternative Viral Mrna Splicing, Sebla B Kutluay, Ann Emery, Srinivasa R Penumutchu, Dana Townsend, Kasyap Tenneti, Michaela K Madison, Amanda M Stukenbroeker, Chelsea Powell, David Jannain, Blanton S Tolbert, Ronald I Swanstrom, Paul D Bieniasz

Open Access Publications

Alternative splicing of HIV-1 mRNAs increases viral coding potential and controls the levels and timing of gene expression. HIV-1 splicing is regulated in part by heterogeneous nuclear ribonucleoproteins (hnRNPs) and their viral target sequences, which typically repress splicing when studied outside their native viral context. Here, we determined the location and extent of hnRNP binding to HIV-1 mRNAs and their impact on splicing in a native viral context. Notably, hnRNP A1, hnRNP A2, and hnRNP B1 bound to many dispersed sites across viral mRNAs. Conversely, hnRNP H1 bound to a few discrete purine-rich sequences, a finding that was mirrored


Las Dos Cosas Versus Exclusive Breastfeeding: A Culturally And Linguistically Exploratory Intervention Study In Hispanic Mothers Living In Kentucky, Ana Maria Linares, Diana Cartagena, Mary Kay Rayens Nov 2019

Las Dos Cosas Versus Exclusive Breastfeeding: A Culturally And Linguistically Exploratory Intervention Study In Hispanic Mothers Living In Kentucky, Ana Maria Linares, Diana Cartagena, Mary Kay Rayens

Nursing Faculty Publications

INTRODUCTION: Formula supplementation among infants of breastfeeding Hispanic immigrants is common practice known as las dos cosas. The purpose of this study was to assess the feasibility, effectiveness, and acceptability of a culturally and linguistically diverse intervention to promote exclusive breastfeeding (EBF) for the first 6 months.

METHODS: A sample of 39 Hispanic pregnant women was recruited and randomly assigned to intervention (n = 20) and control groups (n = 19). The intervention included a peer counselor and professional support, and mothers were followed from pregnancy to 6 months after birth.

RESULTS: After the study, women assigned to …


Cabozantinib Versus Sunitinib For Untreated Patients With Advanced Renal Cell Carcinoma Of Intermediate Or Poor Risk: Subgroup Analysis Of The Alliance A031203 Cabosun Trial, Daniel J George, Colin Hessel, Susan Halabi, M Dror Michaelson, Olwen Hahn, Meghara Walsh, Joel Picus, Eric J Small, Shaker Dakhil, Darren R Feldman, Milan Mangeshkar, Christian Scheffold, Michael J Morris, Toni K Choueiri Nov 2019

Cabozantinib Versus Sunitinib For Untreated Patients With Advanced Renal Cell Carcinoma Of Intermediate Or Poor Risk: Subgroup Analysis Of The Alliance A031203 Cabosun Trial, Daniel J George, Colin Hessel, Susan Halabi, M Dror Michaelson, Olwen Hahn, Meghara Walsh, Joel Picus, Eric J Small, Shaker Dakhil, Darren R Feldman, Milan Mangeshkar, Christian Scheffold, Michael J Morris, Toni K Choueiri

Open Access Publications

Cabozantinib treatment prolonged progression-free survival (PFS) and improved objective response rate (ORR) compared with sunitinib in patients with advanced renal cell carcinoma (RCC) of intermediate or poor risk by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria in the phase II CABOSUN trial (NCT01835158). In the trial, 157 patients were randomized 1:1 to receive cabozantinib or sunitinib, stratified by IMDC risk group and presence of bone metastases. Here, PFS and ORR, both determined by independent radiology committee (IRC), were analyzed by subgroups of baseline characteristics. Cabozantinib treatment was generally associated with improved PFS and ORR versus sunitinib across subgroups, …


The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity In Lipid Membranes: Potential Implication For Its Diverse Biological Action, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu Nov 2019

The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity In Lipid Membranes: Potential Implication For Its Diverse Biological Action, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu

Faculty, Staff and Student Publications

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with …


Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis Oct 2019

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …


Integrated Proteogenomic Characterization Of Clear Cell Renal Cell Carcinoma, David J Clark, Yize Li, Yige Wu, Matthew A Wyczalkowski, Sunantha Sethuraman, Song Cao, Feng Chen, James J Hsieh, Li Ding, Et Al Oct 2019

Integrated Proteogenomic Characterization Of Clear Cell Renal Cell Carcinoma, David J Clark, Yize Li, Yige Wu, Matthew A Wyczalkowski, Sunantha Sethuraman, Song Cao, Feng Chen, James J Hsieh, Li Ding, Et Al

Open Access Publications

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale …


4d Electron Microscopy Of T Cell Activation., Yue Lu, Byung-Kuk Yoo, Alphonsus H C Ng, Jungwoo Kim, Sinchul Yeom, Jau Tang, Milo M Lin, Ahmed H Zewail, James R Heath Oct 2019

4d Electron Microscopy Of T Cell Activation., Yue Lu, Byung-Kuk Yoo, Alphonsus H C Ng, Jungwoo Kim, Sinchul Yeom, Jau Tang, Milo M Lin, Ahmed H Zewail, James R Heath

Articles, Abstracts, and Reports

T cells can be controllably stimulated through antigen-specific or nonspecific protocols. Accompanying functional hallmarks of T cell activation can include cytoskeletal reorganization, cell size increase, and cytokine secretion. Photon-induced near-field electron microscopy (PINEM) is used to image and quantify evanescent electric fields at the surface of T cells as a function of various stimulation conditions. While PINEM signal strength scales with multiple of the biophysical changes associated with T cell functional activation, it mostly strongly correlates with antigen-engagement of the T cell receptors, even under conditions that do not lead to functional T cell activation. PINEM image analysis suggests that …


Burden Of Relapsing-Remitting Multiple Sclerosis On Workers In The Us: A Cross-Sectional Analysis Of Survey Data., Jacqueline A Nicholas, Batul Electricwala, Lulu K Lee, Kristen M Johnson Oct 2019

Burden Of Relapsing-Remitting Multiple Sclerosis On Workers In The Us: A Cross-Sectional Analysis Of Survey Data., Jacqueline A Nicholas, Batul Electricwala, Lulu K Lee, Kristen M Johnson

Neuroscience Articles

BACKGROUND: Multiple sclerosis (MS) is prevalent among working age individuals (20-60 years), leading to high burden on work productivity. Few data are available about the absenteeism and presenteeism in employed individuals with MS in comparison to non-MS personnel. This study aimed to quantify the burden of illness of employed US adults with relapsing-remitting multiple sclerosis (RRMS) and examine burden by levels of work impairment.

METHODS: A retrospective cross-sectional analysis was conducted using patient-reported responses from the US National Health and Wellness Survey (NHWS). Data from NHWS 2015-2016 were analyzed from 196 employed RRMS respondents who were matched 1:4 to employed …


Co-Prescription Network Reveals Social Dynamics Of Opioid Doctor Shopping, Brea L. Perry, Kai Cheng Yang, Patrick Kaminski, Meltem Odabas, Jaehyuk Park, Michelle M. Martel, Carrie B. Oser, Patricia R. Freeman, Yong-Yeol Ahn, Jeffery C. Talbert Oct 2019

Co-Prescription Network Reveals Social Dynamics Of Opioid Doctor Shopping, Brea L. Perry, Kai Cheng Yang, Patrick Kaminski, Meltem Odabas, Jaehyuk Park, Michelle M. Martel, Carrie B. Oser, Patricia R. Freeman, Yong-Yeol Ahn, Jeffery C. Talbert

Psychology Faculty Publications

This paper examines network prominence in a co-prescription network as an indicator of opioid doctor shopping (i.e., fraudulent solicitation of opioids from multiple prescribers). Using longitudinal data from a large commercially insured population, we construct a network where a tie between patients is weighted by the number of shared opioid prescribers. Given prior research suggesting that doctor shopping may be a social process, we hypothesize that active doctor shoppers will occupy central structural positions in this network. We show that network prominence, operationalized using PageRank, is associated with more opioid prescriptions, higher predicted risk for dangerous morphine dosage, opioid overdose, …


Systemic And Local Immunity Following Adoptive Transfer Of Ny-Eso-1 Spear T Cells In Synovial Sarcoma, Indu Ramachandran, Brian A Van Tine, Et Al Oct 2019

Systemic And Local Immunity Following Adoptive Transfer Of Ny-Eso-1 Spear T Cells In Synovial Sarcoma, Indu Ramachandran, Brian A Van Tine, Et Al

2010-2019 OA Pubs

BACKGROUND: Gene-modified autologous T cells expressing NY-ESO-1

METHODS: Four cohorts were included to evaluate antigen expression and preconditioning on efficacy. Clinical responses were assessed by RECIST v1.1. Engineered T-cell persistence was determined by qPCR. Serum cytokines were evaluated by immunoassay. Transcriptomic analyses and immunohistochemistry were performed on tumor biopsies from patients before and after T-cell infusion. Gene-modified T-cells were detected within the TME via an RNAish assay.

RESULTS: Responses across cohorts were affected by preconditioning and intra-tumoral NY-ESO-1 expression. Of the 42 patients reported (data cut-off 4June2018), 1 patient had a complete response, 14 patients had partial responses, 24 patients …


Case 22-2019: A 65-Year-Old Woman With Myopathy., Marinos C. Dalakas Oct 2019

Case 22-2019: A 65-Year-Old Woman With Myopathy., Marinos C. Dalakas

Department of Neurology Faculty Papers

No abstract provided.


Integrating Treatment For Co-Occurring Mental Health Conditions, Amy M Yule, John F Kelly Oct 2019

Integrating Treatment For Co-Occurring Mental Health Conditions, Amy M Yule, John F Kelly

Project ECHO Bibliography

Given the high co-occurrence between alcohol use disorder (AUD) and mental health conditions (MHCs), and the increased morbidity associated with the presence of co-occurring disorders, it is important that co-occurring disorders be identified and both disorders addressed in integrated treatment. Tremendous heterogeneity exists among individuals with co-occurring conditions, and factors related to both AUD and MHCs, including symptom type and acuity, illness severity, the chronicity of symptoms, and recovery capital, should be considered when recommending treatment interventions. This article reviews the prevalence of co-occurring AUD and MHCs, screening tools to identify individuals with symptoms of AUD and MHCs, and subsequent …