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Articles 28561 - 28590 of 77178
Full-Text Articles in Medical Specialties
A Multicenter Analysis Of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy In Retinoblastoma: Implications For Clinical Testing, Deborah H Im, Sarah Pike, Mark W Reid, Chen-Ching Peng, Shreya Sirivolu, Hans E Grossniklaus, G Baker Hubbard, Alison H Skalet, Kellyn N Bellsmith, Carol L. Shields, Sara E Lally, Andrew W Stacey, Bibiana J Reiser, Aaron Nagiel, Rachana Shah, Liya Xu, Jesse L Berry
A Multicenter Analysis Of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy In Retinoblastoma: Implications For Clinical Testing, Deborah H Im, Sarah Pike, Mark W Reid, Chen-Ching Peng, Shreya Sirivolu, Hans E Grossniklaus, G Baker Hubbard, Alison H Skalet, Kellyn N Bellsmith, Carol L. Shields, Sara E Lally, Andrew W Stacey, Bibiana J Reiser, Aaron Nagiel, Rachana Shah, Liya Xu, Jesse L Berry
Wills Eye Hospital Papers
PURPOSE: Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays.
DESIGN: Case series study.
PARTICIPANTS: Sixty-two RB eyes from 55 children and 14 control eyes from 12 children from 4 medical centers.
METHODS: This study included 128 RB AH samples including: diagnostic (DX) samples, samples from eyes undergoing treatment (TX), samples after completing treatment (END), and during bevacizumab injection for radiation therapy after completing RB treatment (BEV). Fourteen-control AH were analyzed for unprocessed analytes (double-stranded DNA …
Multiple Fibrofolliculomas Within A Fibrous Cephalic Plaque In A Patient With Tuberous Sclerosis, Justin Raman, Annie Jin, Jennifer J. Parker, Conor M. Vickers, Daniela M. Proca, Sylvia Hsu, Jason B. Lee
Multiple Fibrofolliculomas Within A Fibrous Cephalic Plaque In A Patient With Tuberous Sclerosis, Justin Raman, Annie Jin, Jennifer J. Parker, Conor M. Vickers, Daniela M. Proca, Sylvia Hsu, Jason B. Lee
Department of Dermatology and Cutaneous Biology Faculty Papers
No abstract provided.
Braf V600e-Mutant Cancers Treated With Vemurafenib Alone Or In Combination With Everolimus, Sorafenib, Or Crizotinib Or With Paclitaxel And Carboplatin (Vem-Plus) Study, Blessie Elizabeth Nelson, Jason Roszik, Filip Janku, David S Hong, Shumei Kato, Aung Naing, Sarina Piha-Paul, Siqing Fu, Apostolia Tsimberidou, Maria Cabanillas, Naifa Lamki Busaidy, Milind Javle, Lauren Averett Byers, John V Heymach, Funda Meric-Bernstam, Vivek Subbiah
Braf V600e-Mutant Cancers Treated With Vemurafenib Alone Or In Combination With Everolimus, Sorafenib, Or Crizotinib Or With Paclitaxel And Carboplatin (Vem-Plus) Study, Blessie Elizabeth Nelson, Jason Roszik, Filip Janku, David S Hong, Shumei Kato, Aung Naing, Sarina Piha-Paul, Siqing Fu, Apostolia Tsimberidou, Maria Cabanillas, Naifa Lamki Busaidy, Milind Javle, Lauren Averett Byers, John V Heymach, Funda Meric-Bernstam, Vivek Subbiah
Faculty, Staff and Student Publications
Combined BRAF + MEK inhibition is FDA approved for BRAF V600E-mutant solid tumors except for colorectal cancer. However, beyond MAPK mediated resistance several other mechanisms of resistance such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway exist among other complex pathways. In the VEM-PLUS study, we performed a pooled analysis of four phase one studies evaluating the safety and efficacy of vemurafenib monotherapy and vemurafenib combined with targeted therapies (sorafenib, crizotinib, or everolimus) or carboplatin plus paclitaxel in advanced solid tumors harboring BRAF V600 mutations. When vemurafenib monotherapy was compared with the combination regimens, no significant differences in OS or …
The Coronavirus Disease 2019 Pandemic Unmasked The Challenges Faced By Early-Stage Faculty In Infectious Diseases: A Call To Action, Erin M Scherer, Martin Backer, Karen Carvajal, Lara Danziger-Isakov, Sharon Frey, Leigh M Howard, Felicia Scaggs Huang, Angelica C Kottkamp, Tara Reid, Maria C Rodriguez-Barradas, Helen C Stankiewicz Karita, Zheyi Teoh, Anna Wald, Jennifer Whitaker, Zanthia Wiley, Igho Ofotokun, Kathryn M Edwards, Infectious Diseases Clinical Research Consortium (Idcrc) Mentorship Program Writing Group
The Coronavirus Disease 2019 Pandemic Unmasked The Challenges Faced By Early-Stage Faculty In Infectious Diseases: A Call To Action, Erin M Scherer, Martin Backer, Karen Carvajal, Lara Danziger-Isakov, Sharon Frey, Leigh M Howard, Felicia Scaggs Huang, Angelica C Kottkamp, Tara Reid, Maria C Rodriguez-Barradas, Helen C Stankiewicz Karita, Zheyi Teoh, Anna Wald, Jennifer Whitaker, Zanthia Wiley, Igho Ofotokun, Kathryn M Edwards, Infectious Diseases Clinical Research Consortium (Idcrc) Mentorship Program Writing Group
Faculty, Staff and Students Publications
The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and …
Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril
Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril
Faculty, Staff and Students Publications
BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.
METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. …
Was Kaposi’S Sarcoma-Associated Herpesvirus Introduced Into China Via The Ancient Silk Road? An Evolutionary Perspective, Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang
Was Kaposi’S Sarcoma-Associated Herpesvirus Introduced Into China Via The Ancient Silk Road? An Evolutionary Perspective, Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang
Nebraska Center for Virology: Faculty Publications
Kaposi’s sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A …
Transcatheter Aortic Valve Replacement-Associated Acute Kidney Injury: An Update, Frederick Berro Rivera, Abdullah Al-Abcha, Marie Francesca Mapua Ansay, John Vincent Usita Magalong, Vincent Anthony Songheng Tang, Hannah May Ona, Karissa Alyanna Miralles, Rausche Sausa, Rodie Abram Florendo Uy, Edgar V. Lerma, Fareed Moses S. Collado, Peter A. Mccullough, Annabelle Santos Volgman
Transcatheter Aortic Valve Replacement-Associated Acute Kidney Injury: An Update, Frederick Berro Rivera, Abdullah Al-Abcha, Marie Francesca Mapua Ansay, John Vincent Usita Magalong, Vincent Anthony Songheng Tang, Hannah May Ona, Karissa Alyanna Miralles, Rausche Sausa, Rodie Abram Florendo Uy, Edgar V. Lerma, Fareed Moses S. Collado, Peter A. Mccullough, Annabelle Santos Volgman
Ateneo School of Medicine and Public Health Publications
Background
Transcatheter aortic valve replacement (TAVR) is a relatively novel minimally invasive procedure for the treatment of symptomatic patients with severe aortic stenosis. Although it has been proven effective in improving mortality and quality of life, TAVR is associated with serious complications, such as acute kidney injury (AKI).
Summary
TAVR-associated AKI is likely due to several factors such as sustained hypotension, transapical approach, volume of contrast use, and baseline low GFR. This narrative review aims to present an overview of the latest literature and evidence regarding the definition of TAVR-associated AKI, its risk factors, and its impact on morbidity and …
Disseminated Juvenile Xanthogranuloma With A Novel Myh9-Flt3 Fusion Presenting As A Blueberry Muffin Rash In A Neonate., Emily E. Clark, Mollie Walton, Lionel M L Chow, J Todd Boyd, M David Yohannan, Shreyas Arya
Disseminated Juvenile Xanthogranuloma With A Novel Myh9-Flt3 Fusion Presenting As A Blueberry Muffin Rash In A Neonate., Emily E. Clark, Mollie Walton, Lionel M L Chow, J Todd Boyd, M David Yohannan, Shreyas Arya
Manuscripts, Articles, Book Chapters and Other Papers
Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received …
Examination Of Geriatric Care Processes Implemented In Level 1 And Level 2 Geriatric Emergency Departments, Ilianna Santangelo, Surriya Ahmad, Shan Liu, Lauren Southerland, Christopher Carpenter, Ula Hwang, Adriane Lesser, Nicole Tidwell, Kevin Biese, Maura Kennedy
Examination Of Geriatric Care Processes Implemented In Level 1 And Level 2 Geriatric Emergency Departments, Ilianna Santangelo, Surriya Ahmad, Shan Liu, Lauren Southerland, Christopher Carpenter, Ula Hwang, Adriane Lesser, Nicole Tidwell, Kevin Biese, Maura Kennedy
Journal of Geriatric Emergency Medicine
Background: Older adults constitute a large and growing proportion of the population and have unique care needs in the emergency department (ED) setting. The geriatric ED accreditation program aims to improve emergency care provided to older adults by standardizing care provided across accredited geriatric EDs (GED) and through implementation of geriatric-specific care processes.
Objective: The purpose of this study was to evaluate select care processes at accredited level 1 and level 2 GEDs.
Methods: This was a cross-sectional analysis of a cohort of level 1 and level 2 GEDs that received accreditation between May 7, 2018 and …
Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery For Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial, Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma
Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery For Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial, Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma
Faculty, Staff and Student Publications
We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant …
Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky
Cd5 Expression By Dendritic Cells Directs T Cell Immunity And Sustains Immunotherapy Responses, Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I Jensen, Yun Zhao, Courtney A Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky
Faculty, Staff and Student Publications
The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T …
Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock
Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock
Wills Eye Hospital Papers
Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.
Objectives: …
Tracking The Evolution Of Esophageal Squamous Cell Carcinoma Under Dynamic Immune Selection By Multi-Omics Sequencing, Sijia Cui, Nicholas Mcgranahan, Jing Gao, Peng Chen, Wei Jiang, Lingrong Yang, Li Ma, Junfang Liao, Tian Xie, Congying Xie, Tariq Enver, Shixiu Wu
Tracking The Evolution Of Esophageal Squamous Cell Carcinoma Under Dynamic Immune Selection By Multi-Omics Sequencing, Sijia Cui, Nicholas Mcgranahan, Jing Gao, Peng Chen, Wei Jiang, Lingrong Yang, Li Ma, Junfang Liao, Tian Xie, Congying Xie, Tariq Enver, Shixiu Wu
Children’s Nutrition Research Center Staff Publications
Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, …
Exploiting Metabolic Vulnerabilities After Anti-Vegf Antibody Therapy In Ovarian Cancer, Deanna Glassman, Mark S Kim, Meredith Spradlin, Sunil Badal, Mana Taki, Pratip Bhattacharya, Prasanta Dutta, Charles V Kingsley, Katherine I Foster, Olamide Animasahun, Jin Heon Jeon, Abhinav Achreja, Anusha Jayaraman, Praveen Kumar, Minal Nenwani, Fulei Wuchu, Emine Bayraktar, Yutuan Wu, Elaine Stur, Lingegowda Mangala, Sanghoon Lee, Timothy A Yap, Shannon N Westin, Livia S Eberlin, Deepak Nagrath, Anil K Sood
Exploiting Metabolic Vulnerabilities After Anti-Vegf Antibody Therapy In Ovarian Cancer, Deanna Glassman, Mark S Kim, Meredith Spradlin, Sunil Badal, Mana Taki, Pratip Bhattacharya, Prasanta Dutta, Charles V Kingsley, Katherine I Foster, Olamide Animasahun, Jin Heon Jeon, Abhinav Achreja, Anusha Jayaraman, Praveen Kumar, Minal Nenwani, Fulei Wuchu, Emine Bayraktar, Yutuan Wu, Elaine Stur, Lingegowda Mangala, Sanghoon Lee, Timothy A Yap, Shannon N Westin, Livia S Eberlin, Deepak Nagrath, Anil K Sood
Faculty, Staff and Student Publications
Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence …
Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang
Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang
Faculty, Staff and Student Publications
Constant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. …
Drug-Like Small Molecules That Inhibit Expression Of The Oncogenic Microrna-21, Matthew D Shortridge, Bhawna Chaubey, Huanyu J Zhang, Thomas Pavelitz, Venkata Vidadala, Changyan Tang, Gregory L Olsen, George A Calin, Gabriele Varani
Drug-Like Small Molecules That Inhibit Expression Of The Oncogenic Microrna-21, Matthew D Shortridge, Bhawna Chaubey, Huanyu J Zhang, Thomas Pavelitz, Venkata Vidadala, Changyan Tang, Gregory L Olsen, George A Calin, Gabriele Varani
Faculty, Staff and Student Publications
We report the discovery of drug-like small molecules that bind specifically to the precursor of the oncogenic and pro-inflammatory microRNA-21 with mid-nanomolar affinity. The small molecules target a local structure at the Dicer cleavage site and induce distinctive structural changes in the RNA, which correlate with specific inhibition of miRNA processing. Structurally conservative single nucleotide substitutions eliminate the conformational change induced by the small molecules, which is also not observed in other miRNA precursors. The most potent of these compounds reduces cellular proliferation and miR-21 levels in cancer cell lines without inhibiting kinases or classical receptors, while closely related compounds …
Batf2 Promotes Hsc Myeloid Differentiation By Amplifying Ifn Response Mediators During Chronic Infection, Duy T Le, Marcus A Florez, Pawel Kus, Brandon T Tran, Bailee Kain, Yingmin Zhu, Kurt Christensen, Antrix Jain, Anna Malovannaya, Katherine Y King
Batf2 Promotes Hsc Myeloid Differentiation By Amplifying Ifn Response Mediators During Chronic Infection, Duy T Le, Marcus A Florez, Pawel Kus, Brandon T Tran, Bailee Kain, Yingmin Zhu, Kurt Christensen, Antrix Jain, Anna Malovannaya, Katherine Y King
Faculty, Staff and Students Publications
Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key factor responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism of BATF2 function in HSCs, we assessed Batf2 KO mice during chronic infection and found that they produced less pro-inflammatory cytokines, less immune cell recruitment to the spleen, and impaired myeloid differentiation with better preservation of HSC capacity compared to WT. Co-IP analysis revealed that BATF2 forms a complex with JUN to amplify pro-inflammatory signaling pathways including CCL5 during infection. Blockade of CCL5 receptors phenocopied Batf2 KO differentiation …
Transcriptome, Proteome, And Protein Synthesis Within The Intracellular Cytomatrix, Tattym E Shaiken, Sandra L Grimm, Mohamad Siam, Amanda Williams, Abdol-Hossein Rezaeian, Daniel Kraushaar, Emily Ricco, Matthew J Robertson, Cristian Coarfa, Antrix Jain, Anna Malovannaya, Fabio Stossi, Antone R Opekun, Alyssa P Price, Julien Dubrulle
Transcriptome, Proteome, And Protein Synthesis Within The Intracellular Cytomatrix, Tattym E Shaiken, Sandra L Grimm, Mohamad Siam, Amanda Williams, Abdol-Hossein Rezaeian, Daniel Kraushaar, Emily Ricco, Matthew J Robertson, Cristian Coarfa, Antrix Jain, Anna Malovannaya, Fabio Stossi, Antone R Opekun, Alyssa P Price, Julien Dubrulle
Faculty, Staff and Students Publications
Despite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains viscous fluid and elastic solid phases. We separated these viscous fluid and solid elastic compartments, which we call the cytosol and cytomatrix, respectively. The distinctive composition of the cytomatrix included structural proteins, ribosomes, and metabolome enzymes. High-throughput analysis revealed unique biosynthetic pathways within the cytomatrix. Enrichment of biosynthetic pathways in the cytomatrix indicated the presence of immobilized biocatalysis. Enzymatic immobilization and segregation can surmount spatial impediments, …
Endothelial-To-Osteoblast Transition In Normal Mouse Bone Development, Song-Chang Lin, Guoyu Yu, Yu-Chen Lee, Jian H Song, Xingzhi Song, Jianhua Zhang, Theocharis Panaretakis, Christopher J Logothetis, Yoshihiro Komatsu, Li-Yuan Yu-Lee, Guocan Wang, Sue-Hwa Lin
Endothelial-To-Osteoblast Transition In Normal Mouse Bone Development, Song-Chang Lin, Guoyu Yu, Yu-Chen Lee, Jian H Song, Xingzhi Song, Jianhua Zhang, Theocharis Panaretakis, Christopher J Logothetis, Yoshihiro Komatsu, Li-Yuan Yu-Lee, Guocan Wang, Sue-Hwa Lin
Faculty, Staff and Student Publications
Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow– and lung-derived ECs underwent transition to OSBs and …
Alternative Polyadenylation Alters Protein Dosage By Switching Between Intronic And 3’Utr Sites, Nicola De Prisco, Caitlin Ford, Nathan D Elrod, Winston Lee, Lauren C Tang, Kai-Lieh Huang, Ai Lin, Ping Ji, Venkata S Jonnakuti, Lia Boyle, Maximilian Cabaj, Salvatore Botta, Katrin Õunap, Karit Reinson, Monica H Wojcik, Jill A Rosenfeld, Weimin Bi, Kristian Tveten, Trine Prescott, Thorsten Gerstner, Audrey Schroeder, Chin-To Fong, Jaya K George-Abraham, Catherine A Buchanan, Andrea Hanson-Khan, Jonathan A Bernstein, Aikaterini A Nella, Wendy K Chung, Vicky Brandt, Marko Jovanovic, Kimara L Targoff, Hari Krishna Yalamanchili, Eric J Wagner, Vincenzo A Gennarino
Alternative Polyadenylation Alters Protein Dosage By Switching Between Intronic And 3’Utr Sites, Nicola De Prisco, Caitlin Ford, Nathan D Elrod, Winston Lee, Lauren C Tang, Kai-Lieh Huang, Ai Lin, Ping Ji, Venkata S Jonnakuti, Lia Boyle, Maximilian Cabaj, Salvatore Botta, Katrin Õunap, Karit Reinson, Monica H Wojcik, Jill A Rosenfeld, Weimin Bi, Kristian Tveten, Trine Prescott, Thorsten Gerstner, Audrey Schroeder, Chin-To Fong, Jaya K George-Abraham, Catherine A Buchanan, Andrea Hanson-Khan, Jonathan A Bernstein, Aikaterini A Nella, Wendy K Chung, Vicky Brandt, Marko Jovanovic, Kimara L Targoff, Hari Krishna Yalamanchili, Eric J Wagner, Vincenzo A Gennarino
Faculty, Staff and Students Publications
Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' untranslated region (3'UTR), introns, or exons. Most studies focus on APA within the 3'UTR; however, here, we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function …
Deepbend: An Interpretable Model Of Dna Bendability, Samin Rahman Khan, Sadman Sakib, M Sohel Rahman, Md Abul Hassan Samee
Deepbend: An Interpretable Model Of Dna Bendability, Samin Rahman Khan, Sadman Sakib, M Sohel Rahman, Md Abul Hassan Samee
Faculty, Staff and Students Publications
The bendability of genomic DNA impacts chromatin packaging and protein-DNA binding. However, we do not have a comprehensive understanding of the motifs influencing DNA bendability. Recent high-throughput technologies such as Loop-Seq offer an opportunity to address this gap but the lack of accurate and interpretable machine learning models still remains. Here we introduce DeepBend, a convolutional neural network model with convolutions designed to directly capture the motifs underlying DNA bendability and their periodic occurrences or relative arrangements that modulate bendability. DeepBend consistently performs on par with alternative models while giving an extra edge through mechanistic interpretations. Besides confirming the known …
The Use Of Characteristics And Indicators Of Body Construction As Predictors In The Identification Of The Angle Values Of The Physiological Curves Of The Spine In Sequential Objective Testing - Mathematical Models, Jacek Tuz, Adam Maszczyk, Anna Zwierzchowska
The Use Of Characteristics And Indicators Of Body Construction As Predictors In The Identification Of The Angle Values Of The Physiological Curves Of The Spine In Sequential Objective Testing - Mathematical Models, Jacek Tuz, Adam Maszczyk, Anna Zwierzchowska
Baltic Journal of Health and Physical Activity
Introduction: The physiological curvatures of the spine in the sagittal plane are constantly evolving along with changes in the structure and proportions of the body and physical activity. The aim of this study is to identify and assess the strength of the influence of body features and indices on the values of lumbar lordosis and thoracic kyphosis angles with the use of a mathematical model. In the years 2006–2016, 1,314 female students aged ( ± SD 19.7 ± 0.4) (min.–max. 18.1–22.5) were examined.
Materials and Methods. The following measurements were made: body mass (BM), body height (BH), waist circumference (WC), …
Evaluating Implementation And Barriers To Sustainability Of An Asthma Clinical Quality Improvement Project, Holly Uphold Phd, Ms, Diane Liu Md, Faap
Evaluating Implementation And Barriers To Sustainability Of An Asthma Clinical Quality Improvement Project, Holly Uphold Phd, Ms, Diane Liu Md, Faap
Journal of Nursing & Interprofessional Leadership in Quality & Safety
Purpose and Objectives
Asthma is an important public health issue in Utah and quality asthma care is essential to addressing the burden of asthma. The purpose of this initiative was to evaluate clinical asthma quality improvement (QI) program delivery formats and identify barriers to sustaining QI processes.
Intervention Approach
The focus of the intervention was to improve clinical asthma care through reducing variation in clinician knowledge about recommended asthma care and facilitating process improvements in asthma care delivery using Academic Detailing (AD) and Learning Collaboratives (LC) QI delivery formats.
Evaluation Methods
A pre/post-test design was used to compare improvements between …
A Doctor For The Common People, Robyn Oro
A Doctor For The Common People, Robyn Oro
Notes from the Archives
No abstract provided.
Breast Cancer Knowledge Among Students At A State Comprehensive University, Calvin Odhiambo, Shimia Hunter
Breast Cancer Knowledge Among Students At A State Comprehensive University, Calvin Odhiambo, Shimia Hunter
Teacher-Scholar: The Journal of the State Comprehensive University
Background: Breast cancer is the most common cancer among women worldwide and the second-leading cause of death among women in the United States. While lack of knowledge about breast cancer is a key factor in breast cancer mortality, little is known about breast cancer knowledge among women and men under the age of 30. The goal of the current study was to investigate the knowledge and awareness of breast cancer among female and male undergraduate students at a State Comprehensive University in the Southeastern United States.
Methods: This was a cross-sectional survey of 265 male and female undergraduate …
Acute Systemic Infection-Associated Russell Body Gastroesophagitis: A Case Report And Literature Review, Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang
Acute Systemic Infection-Associated Russell Body Gastroesophagitis: A Case Report And Literature Review, Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang
Division of Gastroenterology and Hepatology Faculty Papers
Russell body esophagitis/gastritis (RBG) is a rare gastrointestinal inflammatory condition characterized by accumulation of plasma cells containing dense eosinophilic cytoplasmic inclusions, i.e., Russell bodies. Herein, we report a case of RBG in a patient with a systemic inflammation background. A 61-year-old female presented with oral infection. Upper gastrointestinal endoscopy revealed patchy salmon-colored esophageal mucosa proximally to the gastroesophageal junction, suggestive of “Barrett’s esophagus”. Histologic examination of the biopsy tissue from the lower esophagus showed diffuse lymphoplasmacytic infiltration with abundant admixed enlarged plasma cells (Mott cells) containing bright eosinophilic, round, dense, homogenous inclusions (Russell bodies) in cytoplasm. Immunohistochemical study demonstrated membranous …
Profibrotic Behavior Of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness, Benjamin A. Hendy, Jolanta Fertala, Thema Nicholson, Joseph A. Abboud, Surena Namdari, Andrzej Fertala
Profibrotic Behavior Of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness, Benjamin A. Hendy, Jolanta Fertala, Thema Nicholson, Joseph A. Abboud, Surena Namdari, Andrzej Fertala
Department of Orthopaedic Surgery Faculty Papers
BACKGROUND AND AIMS: Arthrofibrosis is a severe scarring condition characterized by joint stiffness and pain. Fundamental to developing arthrofibrotic scars is the accelerated production of procollagen I, a precursor of collagen I molecules that form fibrotic deposits in affected joints. The procollagen I production mechanism comprises numerous elements, including enzymes, protein chaperones, and growth factors. This study aimed to elucidate the differences in the production of vital elements of this mechanism in surgical patients who developed significant posttraumatic arthrofibrosis and those who did not.
METHODS: We studied a group of patients who underwent shoulder arthroscopic repair of the rotator cuff. …
Factors Associated With Response To Growth Hormone In Pediatric Growth Disorders: Results Of A 5-Year Registry Analysis, Judith L. Ross, Moshe Fridman, Nicky Kelepouris, Kristine Murray, Nils Krone, Michel Polak, Tilman R Rohrer, Alberto Pietropoli, Neil Lawrence, Philippe Backeljauw
Factors Associated With Response To Growth Hormone In Pediatric Growth Disorders: Results Of A 5-Year Registry Analysis, Judith L. Ross, Moshe Fridman, Nicky Kelepouris, Kristine Murray, Nils Krone, Michel Polak, Tilman R Rohrer, Alberto Pietropoli, Neil Lawrence, Philippe Backeljauw
Department of Pediatrics Faculty Papers
Context: Growth hormone (GH) therapy can increase linear growth in patients with growth hormone deficiency (GHD), Turner syndrome (TS), Noonan syndrome (NS), and Prader-Willi syndrome (PWS), although outcomes vary by disease state.
Objective: To assess growth and identify factors associated with growth response with long-term GH therapy.
Methods: Data from pediatric patients with GHD, TS, NS, and PWS obtained at GH treatment initiation (baseline) and annually for 5 years in the ANSWER Program and NordiNet® IOS were analyzed retrospectively. Height standard deviation score (HSDS) was assessed over time, and multivariate analyses determined variables with significant positive effects on growth outcomes …
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
School of Public Health Faculty Publications
Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.
Akt/Mtor Signaling Modulates Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Metastatic Breast Cancers, Maysa M. Abu-Khalaf, K. Alex Hodge, Christos Hatzis, Elisa Baldelli, Emna El Gazzah, Frances Valdes, William M. Sikov, Monica M. Mita, Neelima Denduluri, Rita Murphy, Daniel Zelterman, Lance Liotta
Akt/Mtor Signaling Modulates Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Metastatic Breast Cancers, Maysa M. Abu-Khalaf, K. Alex Hodge, Christos Hatzis, Elisa Baldelli, Emna El Gazzah, Frances Valdes, William M. Sikov, Monica M. Mita, Neelima Denduluri, Rita Murphy, Daniel Zelterman, Lance Liotta
Kimmel Cancer Center Faculty Papers
Endocrine therapy (ET) in combination with CDK4/6 inhibition is routinely used as first-line treatment for HR+/HER2− metastatic breast cancer (MBC) patients. However, 30–40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven protein/phosphoprotein-based approach to identify predictive markers of response to ET plus CDK4/6 inhibition in pre-treatment tissue biopsies. Pathway-centered signaling profiles were generated from microdissected tumor epithelia and surrounding stroma/immune cells using the reverse phase protein microarray. Phosphorylation levels of the CDK4/6 downstream substrates Rb (S780) and FoxM1 (T600) were higher in patients with progressive disease (PD) compared to responders (p = …