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Full-Text Articles in Medicine and Health Sciences
Segregated Patterns Of Hospital Care Delivery And Health Outcomes, Sunny C Lin, J. Gmerice Hammond, Michael Esposito, Cassandra Majewski, Randi E Foraker, Karen E Joynt Maddox
Segregated Patterns Of Hospital Care Delivery And Health Outcomes, Sunny C Lin, J. Gmerice Hammond, Michael Esposito, Cassandra Majewski, Randi E Foraker, Karen E Joynt Maddox
2020-Current year OA Pubs
IMPORTANCE: Residential segregation has been shown to be a root cause of racial inequities in health outcomes, yet little is known about current patterns of racial segregation in where patients receive hospital care or whether hospital segregation is associated with health outcomes. Filling this knowledge gap is critical to implementing policies that improve racial equity in health care.
OBJECTIVE: To characterize contemporary patterns of racial segregation in hospital care delivery, identify market-level correlates, and determine the association between hospital segregation and health outcomes.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of US hospital referral regions (HRRs) used 2018 Medicare claims, …
Diagnostic And Commensal Staphylococcus Pseudintermedius Genomes Reveal Niche Adaptation Through Parallel Selection Of Defense Mechanisms, Sanjam S Sawhney, Rhiannon C Vargas, Meghan A Wallace, Carol E Muenks, Brian V Lubbers, Stephanie A Fritz, Carey-Ann D Burnham, Gautam Dantas
Diagnostic And Commensal Staphylococcus Pseudintermedius Genomes Reveal Niche Adaptation Through Parallel Selection Of Defense Mechanisms, Sanjam S Sawhney, Rhiannon C Vargas, Meghan A Wallace, Carol E Muenks, Brian V Lubbers, Stephanie A Fritz, Carey-Ann D Burnham, Gautam Dantas
2020-Current year OA Pubs
Staphylococcus pseudintermedius is historically understood as a prevalent commensal and pathogen of dogs, though modern clinical diagnostics reveal an expanded host-range that includes humans. It remains unclear whether differentiation across S. pseudintermedius populations is driven primarily by niche-type or host-species. We sequenced 501 diagnostic and commensal isolates from a hospital, veterinary diagnostic laboratory, and within households in the American Midwest, and performed a comparative genomics investigation contrasting human diagnostic, animal diagnostic, human colonizing, pet colonizing, and household-surface S. pseudintermedius isolates. Though indistinguishable by core and accessory gene architecture, diagnostic isolates harbor more encoded and phenotypic resistance, whereas colonizing and surface …
Personal Factors And Baseline Function In Patients Undergoing Non-Operative Management For Chronic Hip-Related Groin Pain: A Cross-Sectional Study, Rebecca D Demargel, Karen Steger-May, Simon Haroutounian, Patricia Zorn, Abby Cheng, John C Clohisy, Marcie Harris-Hayes
Personal Factors And Baseline Function In Patients Undergoing Non-Operative Management For Chronic Hip-Related Groin Pain: A Cross-Sectional Study, Rebecca D Demargel, Karen Steger-May, Simon Haroutounian, Patricia Zorn, Abby Cheng, John C Clohisy, Marcie Harris-Hayes
2020-Current year OA Pubs
AIM: Little is known about the relationship between personal factors and perception of hip-related function among patients with chronic hip-related groin pain (HRGP) seeking non-operative management. This analysis was performed to determine if depressive symptoms, central sensitisation, movement evoked pain (MEP), pressure hypersensitivity and activity level were associated with patients' perception of hip-related function, represented by the International Hip Outcome Tool (iHOT-33).
METHODS: This cross-sectional study used baseline data from a pilot randomised clinical trial. Participants had anterior hip symptoms for at least 3 of the past 12 months reproduced on examination. Depressive symptoms, central sensitisation and activity level were …
In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Premal H Thaker, Et Al.
In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Premal H Thaker, Et Al.
2020-Current year OA Pubs
In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …
Unc-49 Is A Redox-Sensitive Gabaa Receptor That Regulates The Mitochondrial Unfolded Protein Response Cell Nonautonomously, Franziska Pohl, Allison L Germann, Jack Mao, Sydney Hou, Bayode Bakare, Paul Kong Thoo Lin, Kyari Yates, Michael L Nonet, Gustav Akk, Kerry Kornfeld, Jason M Held
Unc-49 Is A Redox-Sensitive Gabaa Receptor That Regulates The Mitochondrial Unfolded Protein Response Cell Nonautonomously, Franziska Pohl, Allison L Germann, Jack Mao, Sydney Hou, Bayode Bakare, Paul Kong Thoo Lin, Kyari Yates, Michael L Nonet, Gustav Akk, Kerry Kornfeld, Jason M Held
2020-Current year OA Pubs
The γ-aminobutyric acid-mediated (GABAergic) system participates in many aspects of organismal physiology and disease, including proteostasis, neuronal dysfunction, and life-span extension. Many of these phenotypes are also regulated by reactive oxygen species (ROS), but the redox mechanisms linking the GABAergic system to these phenotypes are not well defined. Here, we report that GABAergic redox signaling cell nonautonomously activates many stress response pathways in
Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.
Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.
2020-Current year OA Pubs
Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74
Description Of The Content And Quality Of Publicly Available Information On The Internet About Inhaled Volatile Anesthesia And Total Intravenous Anesthesia: Descriptive Study, Xinwen Hu, Bethany R Tellor Pennington, Michael S Avidan, Sachin Kheterpal, Nastassjia G Debourbon, Mary C Politi
Description Of The Content And Quality Of Publicly Available Information On The Internet About Inhaled Volatile Anesthesia And Total Intravenous Anesthesia: Descriptive Study, Xinwen Hu, Bethany R Tellor Pennington, Michael S Avidan, Sachin Kheterpal, Nastassjia G Debourbon, Mary C Politi
2020-Current year OA Pubs
BACKGROUND: More than 300 million patients undergo surgical procedures requiring anesthesia worldwide annually. There are 2 standard-of-care general anesthesia administration options: inhaled volatile anesthesia (INVA) and total intravenous anesthesia (TIVA). There is limited evidence comparing these methods and their impact on patient experiences and outcomes. Patients often seek this information from sources such as the internet. However, the majority of websites on anesthesia-related topics are not comprehensive, updated, and fully accurate. The quality and availability of web-based patient information about INVA and TIVA have not been sufficiently examined.
OBJECTIVE: This study aimed to (1) assess information on the internet about …
Reverse Engineering And 3d Printing Of Medical Devices For Drug Delivery And Drug-Embedded Anatomic Implants, Anusha Elumalai, Yash Nayak, Aravinda K Ganapathy, David Chen, Karthik Tappa, Udayabhanu Jammalamadaka, Grace Bishop, David H Ballard
Reverse Engineering And 3d Printing Of Medical Devices For Drug Delivery And Drug-Embedded Anatomic Implants, Anusha Elumalai, Yash Nayak, Aravinda K Ganapathy, David Chen, Karthik Tappa, Udayabhanu Jammalamadaka, Grace Bishop, David H Ballard
2020-Current year OA Pubs
In recent years, 3D printing (3DP) has advanced traditional medical treatments. This review explores the fusion of reverse engineering and 3D printing of medical implants, with a specific focus on drug delivery applications. The potential for 3D printing technology to create patient-specific implants and intricate anatomical models is discussed, along with its ability to address challenges in medical treatment. The article summarizes the current landscape, challenges, benefits, and emerging trends of using 3D-printed formulations for medical implantation and drug delivery purposes.
Ex Vivo To In Vivo Model Of Malignant Peripheral Nerve Sheath Tumors For Precision Oncology, Alex T Larsson, Himanshi Bhatia, Xiaochun Zhang, Daniel Schefer, Kuangying Yang, Yang Lyu, Carina A Dehner, John S A Chrisinger, Kevin He, Angela C Hirbe, Et Al.
Ex Vivo To In Vivo Model Of Malignant Peripheral Nerve Sheath Tumors For Precision Oncology, Alex T Larsson, Himanshi Bhatia, Xiaochun Zhang, Daniel Schefer, Kuangying Yang, Yang Lyu, Carina A Dehner, John S A Chrisinger, Kevin He, Angela C Hirbe, Et Al.
2020-Current year OA Pubs
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).
METHODS: Genomic analysis was performed on all PDX-tumor pairs. Selected PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, …
Protein Kinase Signaling Networks Driven By Oncogenic Gq/11 In Uveal Melanoma Identified By Phosphoproteomic And Bioinformatic Analyses, Michael D Onken, Petra Erdmann-Gilmore, Qiang Zhang, Kisan Thapa, Emily King, Kevin M Kaltenbronn, Sarah E Noda, Carol M Makepeace, Dennis Goldfarb, Özgün Babur, R Reid Townsend, Kendall J Blumer
Protein Kinase Signaling Networks Driven By Oncogenic Gq/11 In Uveal Melanoma Identified By Phosphoproteomic And Bioinformatic Analyses, Michael D Onken, Petra Erdmann-Gilmore, Qiang Zhang, Kisan Thapa, Emily King, Kevin M Kaltenbronn, Sarah E Noda, Carol M Makepeace, Dennis Goldfarb, Özgün Babur, R Reid Townsend, Kendall J Blumer
2020-Current year OA Pubs
Metastatic uveal melanoma (UM) patients typically survive only 2 to 3 years because effective therapy does not yet exist. Here, to facilitate the discovery of therapeutic targets in UM, we have identified protein kinase signaling mechanisms elicited by the drivers in 90% of UM tumors: mutant constitutively active G protein α-subunits encoded by GNAQ (Gq) or GNA11 (G11). We used the highly specific Gq/11 inhibitor FR900359 (FR) to elucidate signaling networks that drive proliferation, metabolic reprogramming, and dedifferentiation of UM cells. We determined the effects of FR on the proteome and phosphoproteome of UM cells as indicated by bioinformatic analyses …
Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al.
Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al.
2020-Current year OA Pubs
BACKGROUND: Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness.
METHODS: We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants …
Plain Language Summary Of The Topaz-1 Study: Durvalumab And Chemotherapy For Advanced Biliary Tract Cancer, Do-Youn Oh, Benjamin Tan, Et Al.
Plain Language Summary Of The Topaz-1 Study: Durvalumab And Chemotherapy For Advanced Biliary Tract Cancer, Do-Youn Oh, Benjamin Tan, Et Al.
2020-Current year OA Pubs
WHAT IS THIS SUMMARY ABOUT?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or …
D-Dimer Predicts Venous Thromboembolism In Multiple Myeloma: A Nested Case-Control Study, Kristen M Sanfilippo, Mark A Fiala, Daniel Feinberg, Harsha Tathireddy, Thomas Girard, Ravi Vij, Jorge Di Paola, Brian F Gage
D-Dimer Predicts Venous Thromboembolism In Multiple Myeloma: A Nested Case-Control Study, Kristen M Sanfilippo, Mark A Fiala, Daniel Feinberg, Harsha Tathireddy, Thomas Girard, Ravi Vij, Jorge Di Paola, Brian F Gage
2020-Current year OA Pubs
BACKGROUND: Clinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment.
OBJECTIVES: We sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM.
METHODS: We identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the …
Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson
Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson
2020-Current year OA Pubs
TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in …
Scientific Document Development Standards For The Society Of Cardiovascular Computed Tomography (Scct): A Statement From The Scct Guidelines Committee, Lauren A Baldassarre, Lynne Koweek, Daniele Andreini, Kelley Branch, Dawn Brennaman, Ricardo P J Budde, Stacy De La O, Timothy Fairbairn, Sandeep S Hedgire, Jonathan R Weir-Mccall, Pam K Woodard, Dennis Wong, Marcus Y Chen, Scct Guidelines Committee
Scientific Document Development Standards For The Society Of Cardiovascular Computed Tomography (Scct): A Statement From The Scct Guidelines Committee, Lauren A Baldassarre, Lynne Koweek, Daniele Andreini, Kelley Branch, Dawn Brennaman, Ricardo P J Budde, Stacy De La O, Timothy Fairbairn, Sandeep S Hedgire, Jonathan R Weir-Mccall, Pam K Woodard, Dennis Wong, Marcus Y Chen, Scct Guidelines Committee
2020-Current year OA Pubs
The Society of Cardiovascular Computed Tomography (SCCT) is an international community of physicians, scientists and technologists advocating for research, education, and clinical excellence in the use of cardiovascular computed tomography (CCT). SCCT members are committed to improving health outcomes through effective use of CCT. The SCCT routinely authors, endorses, and jointly collaborates on scientific documents that reflect the best available evidence and expert consensus supported in practice of CCT. This paper outlines SCCT's methodology for developing scientific documents. It was formulated by members of the SCCT Guidelines Committee and approved by the SCCT Board of Directors.
Epigenetic Regulation During Cancer Transitions Across 11 Tumour Types, Nadezhda V Terekhanova, Alla Karpova, Wen-Wei Liang, Siqi Chen, Yize Li, Austin N Southard-Smith, Michael D Iglesia, Michael C Wendl, Reyka G Jayasinghe, Jingxian Liu, Yizhe Song, Song Cao, Andrew Houston, Xiuting Liu, Matthew A Wyczalkowski, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Shinkle, Nataly Naser Al Deen, John M Herndon, Jacqueline Mudd, Kazuhito Sato, Omar M Ibrahim, Chia-Kuei Mo, Sara E Chasnoff, Jason M Held, Russell Pachynski, Julie K Schwarz, William E Gillanders, Albert H Kim, Ravi Vij, John F Dipersio, Sidharth V Puram, Milan G Chheda, Katherine C Fuh, David G Denardo, Ryan C Fields, Feng Chen, Li Ding, Et Al.
Epigenetic Regulation During Cancer Transitions Across 11 Tumour Types, Nadezhda V Terekhanova, Alla Karpova, Wen-Wei Liang, Siqi Chen, Yize Li, Austin N Southard-Smith, Michael D Iglesia, Michael C Wendl, Reyka G Jayasinghe, Jingxian Liu, Yizhe Song, Song Cao, Andrew Houston, Xiuting Liu, Matthew A Wyczalkowski, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Shinkle, Nataly Naser Al Deen, John M Herndon, Jacqueline Mudd, Kazuhito Sato, Omar M Ibrahim, Chia-Kuei Mo, Sara E Chasnoff, Jason M Held, Russell Pachynski, Julie K Schwarz, William E Gillanders, Albert H Kim, Ravi Vij, John F Dipersio, Sidharth V Puram, Milan G Chheda, Katherine C Fuh, David G Denardo, Ryan C Fields, Feng Chen, Li Ding, Et Al.
2020-Current year OA Pubs
Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis
Momelotinib In Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials, Jean-Jacques Kiladjian, Stephen T. Oh, Et Al.
Momelotinib In Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials, Jean-Jacques Kiladjian, Stephen T. Oh, Et Al.
2020-Current year OA Pubs
The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 10
Patient-Reported Outcomes And Quality Of Life In Anemic And Symptomatic Patients With Myelofibrosis: Results From The Momentum Study, Ruben A. Mesa, Stephen T. Oh, Et Al.
Patient-Reported Outcomes And Quality Of Life In Anemic And Symptomatic Patients With Myelofibrosis: Results From The Momentum Study, Ruben A. Mesa, Stephen T. Oh, Et Al.
2020-Current year OA Pubs
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score …
Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López
Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López
2020-Current year OA Pubs
Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in …
Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al.
Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al.
2020-Current year OA Pubs
BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.
METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, …
Hepatic Pyruvate And Alanine Metabolism Are Critical And Complementary For Maintenance Of Antioxidant Capacity And Resistance To Oxidative Insult, Nicole K H Yiew, Joel H Vazquez, Michael R Martino, Stefanie Kennon-Mcgill, Jake R Price, Felicia D Allard, Eric U Yee, Alexander J Layman, Laura P James, Kyle S Mccommis, Brian N Finck, Mitchell R Mcgill
Hepatic Pyruvate And Alanine Metabolism Are Critical And Complementary For Maintenance Of Antioxidant Capacity And Resistance To Oxidative Insult, Nicole K H Yiew, Joel H Vazquez, Michael R Martino, Stefanie Kennon-Mcgill, Jake R Price, Felicia D Allard, Eric U Yee, Alexander J Layman, Laura P James, Kyle S Mccommis, Brian N Finck, Mitchell R Mcgill
2020-Current year OA Pubs
OBJECTIVE: Mitochondrial pyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, and NADH production. As a result, the mitochondrial pyruvate carrier (MPC) complex has emerged as a promising therapeutic target in metabolic diseases. Clinical trials are currently underway. However, recent in vitro data indicate that MPC inhibition diverts glutamine/glutamate away from glutathione synthesis and toward glutaminolysis to compensate for loss of pyruvate oxidation, possibly sensitizing cells to oxidative insult. Here, we explored this in vivo using the clinically relevant acetaminophen (APAP) overdose model of acute liver injury, which is driven by oxidative stress.
METHODS: We used pharmacological and genetic approaches …
A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn
A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn
2020-Current year OA Pubs
Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …
Targeted Proteomic Quantitation Of Nrf2 Signaling And Predictive Biomarkers In Hnscc, Nathan T Wamsley, Emily M Wilkerson, Kyle M Lapak, Robert W Sprung, Petra Erdmann Gilmore, Sophie P Gerndt, Ryan S Jackson, Randal C Paniello, Patrik Pipkorn, Sidharth V Puram, Jason T Rich, Reid R Townsend, José P Zevallos, Paul Zolkind, Dennis Goldfarb, Michael B Major, Et Al.
Targeted Proteomic Quantitation Of Nrf2 Signaling And Predictive Biomarkers In Hnscc, Nathan T Wamsley, Emily M Wilkerson, Kyle M Lapak, Robert W Sprung, Petra Erdmann Gilmore, Sophie P Gerndt, Ryan S Jackson, Randal C Paniello, Patrik Pipkorn, Sidharth V Puram, Jason T Rich, Reid R Townsend, José P Zevallos, Paul Zolkind, Dennis Goldfarb, Michael B Major, Et Al.
2020-Current year OA Pubs
The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on …
Reducing Length Of Antibiotics For Children With Ear Infections: Protocol For A Cluster-Randomized Trial In The Usa, Amy Keith, Timothy C Jenkins, Sonja O'Leary, Amy B Stein, Sophie E Katz, Jason Newland, Deborah J Rinehart, Aiden Gilbert, Sherry Dodd, Cindy M Terrill, Holly M Frost
Reducing Length Of Antibiotics For Children With Ear Infections: Protocol For A Cluster-Randomized Trial In The Usa, Amy Keith, Timothy C Jenkins, Sonja O'Leary, Amy B Stein, Sophie E Katz, Jason Newland, Deborah J Rinehart, Aiden Gilbert, Sherry Dodd, Cindy M Terrill, Holly M Frost
2020-Current year OA Pubs
No abstract provided.
Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.
Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.
2020-Current year OA Pubs
OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2
DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.
RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …
Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas
Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas
2020-Current year OA Pubs
BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.
METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of …
Trapeziectomy With Ligament Reconstruction/ Suspensionplasty Compared To Suture Tape Suspensionplasty For The Surgical Treatment Of Advanced Thumb Carpometacarpal Osteoarthritis, Nishant Dwivedi, Ryan P Calfee, Lindley B Wall, Martin I Boyer, David Brogan, Christopher J Dy, Charles A Goldfarb
Trapeziectomy With Ligament Reconstruction/ Suspensionplasty Compared To Suture Tape Suspensionplasty For The Surgical Treatment Of Advanced Thumb Carpometacarpal Osteoarthritis, Nishant Dwivedi, Ryan P Calfee, Lindley B Wall, Martin I Boyer, David Brogan, Christopher J Dy, Charles A Goldfarb
2020-Current year OA Pubs
PURPOSE: Trapeziectomy with tendon reconstruction/suspensionplasty (TRS) is the most commonly performed surgical procedure in the United States for treatment of thumb carpometacarpal (CMC) osteoarthritis (OA). Trapeziectomy with suture tape suspensionplasty (STS) has been used recently at the study institution as an alternative surgical treatment option with perceived benefits of earlier return to function and reduced operative time. The purpose of this study was to compare patient outcomes following TRS versus STS for treatment of thumb CMC OA.
METHODS: All patients who underwent primary, isolated TRS or STS for treatment of thumb CMC OA between 1/1/2014 and 9/1/2020 were analyzed. We …
Outcomes Of Therapy And Ulnar Nerve Transposition For Elbow Stiffness After Pediatric Medial Epicondyle Fractures, Emma R Payne, Lindley B Wall, Stacy Baker, Valeri Calhoun, Summer Roberts, Charles A Goldfarb
Outcomes Of Therapy And Ulnar Nerve Transposition For Elbow Stiffness After Pediatric Medial Epicondyle Fractures, Emma R Payne, Lindley B Wall, Stacy Baker, Valeri Calhoun, Summer Roberts, Charles A Goldfarb
2020-Current year OA Pubs
PURPOSE: Following medial epicondyle fractures, a subset of pediatric patients has persistent limitations in elbow motion. This study soughted to understand the patient characteristics of this group and to assess the effectiveness of intensive therapy and ulnar nerve transposition in improving elbow range of motion and patient-reported outcomes.
METHODS: A cohort of 31 pediatric patients with stiffness after elbow trauma was narrowed to 8 pediatric patients (7 female) ranging in age from 9 to 14 years, who were diagnosed with medial epicondyle fractures and underwent intensive therapy and ulnar nerve transposition with or without elbow joint release. We collected demographic …
Evaluation Of The Efficacy And Safety Of Bempedoic Acid In Women And Men: Pooled Analyses From Phase 3 Trials, Anne C Goldberg, Maciej Banach, Alberico L Catapano, P Barton Duell, Lawrence A Leiter, Jeffrey C Hanselman, Lei Lei, G B John Mancini
Evaluation Of The Efficacy And Safety Of Bempedoic Acid In Women And Men: Pooled Analyses From Phase 3 Trials, Anne C Goldberg, Maciej Banach, Alberico L Catapano, P Barton Duell, Lawrence A Leiter, Jeffrey C Hanselman, Lei Lei, G B John Mancini
2020-Current year OA Pubs
BACKGROUND AND AIMS: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.
METHODS: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed …
S-Adenosylmethionine And Nicotinamide Riboside Therapy In Arts Syndrome: A Case Report And Literature Review, Angela Lee, Renatta Knox, Margaret Reynolds, Erin Mcroy, Hoanh Nguyen
S-Adenosylmethionine And Nicotinamide Riboside Therapy In Arts Syndrome: A Case Report And Literature Review, Angela Lee, Renatta Knox, Margaret Reynolds, Erin Mcroy, Hoanh Nguyen
2020-Current year OA Pubs
Phospho-ribosyl-pyrophosphate synthetase 1 (PRPS1) deficiency is secondary to loss of function variants in