tbuckley/cabot-search huggingface dataset:
Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring
Authors: Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2020)

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL1 fusion oncogene, which in turn translates into a BCR-ABL oncoprotein.Four tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, dasatinib, and bosutinib are approved by the United States Food and Drug Administration for first-line treatment of newly diagnosed CML in chronic phase (CML-CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses, but they had no impact on survival prolongation, likely because of the existence of highly effective salvage therapies for patients who have a cytogenetic relapse with frontline TKI.For CML post failure on frontline therapy, second-line options include second and third generation TKIs. Although potent and selective, these exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR-ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Even among older patients who have a cytogenetic relapse post failure on all TKIs, they can maintain long-term survival if they continue on a daily most effective/less toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan, others).
TNFAIP3 Interacting Protein 3 Overexpression Suppresses Nonalcoholic Steatohepatitis by Blocking TAK1 Activation
Authors: Dan Liu, Peng Zhang, Junjie Zhou, Rufang Liao, Yan Che, Mao-Mao Gao, Jiaqi Sun, Jingjing Cai, Xu Cheng, Yongping Huang, Guopeng Chen, Hongyu Nie, Yan-Xiao Ji, Xiao-Jing Zhang, Zan Huang, Haibo Xu, Zhi-Gang She, Hongliang Li
Journal: Cell Metabolism (2020)
Characterisation and evaluation of the regenerative capacity of Stro-4+ enriched bone marrow mesenchymal stromal cells using bovine extracellular matrix hydrogel and a novel biocompatible melt electro-written medical-grade polycaprolactone scaffold
Authors: C. Black, J.M. Kanczler, M.C. de Andrés, L.J. White, F.M. Savi, O. Bas, S. Saifzadeh, J. Henkel, A. Zannettino, S. Gronthos, M.A. Woodruff, D.W. Hutmacher, R.O.C. Oreffo
Journal: Biomaterials (2020)

Many skeletal tissue regenerative strategies centre around the multifunctional properties of bone marrow derived stromal cells (BMSC) or mesenchymal stem/stromal cells (MSC)/bone marrow derived skeletal stem cells (SSC). Specific identification of these particular stem cells has been inconclusive. However, enriching these heterogeneous bone marrow cell populations with characterised skeletal progenitor markers has been a contributing factor in successful skeletal bone regeneration and repair strategies. In the current studies we have isolated, characterised and enriched ovine bone marrow mesenchymal stromal cells (oBMSCs) using a specific antibody, Stro-4, examined their multipotential differentiation capacity and, in translational studies combined Stro-4+ oBMSCs with a bovine extracellular matrix (bECM) hydrogel and a biocompatible melt electro-written medical-grade polycaprolactone scaffold, and tested their bone regenerative capacity in a small in vivo, highly vascularised, chick chorioallantoic membrane (CAM) model and a preclinical, critical-sized ovine segmental tibial defect model. Proliferation rates and CFU-F formation were similar between unselected and Stro-4+ oBMSCs. Col1A1, Col2A1, mSOX-9, PPARG gene expression were upregulated in respective osteogenic, chondrogenic and adipogenic culture conditions compared to basal conditions with no significant difference between Stro-4+ and unselected oBMSCs. In contrast, proteoglycan expression, alkaline phosphatase activity and adipogenesis were significantly upregulated in the Stro-4+ cells. Furthermore, with extended cultures, the oBMSCs had a predisposition to maintain a strong chondrogenic phenotype. In the CAM model Stro-4+ oBMSCs/bECM hydrogel was able to induce bone formation at a femur fracture site compared to bECM hydrogel and control blank defect alone. Translational studies in a critical-sized ovine tibial defect showed autograft samples contained significantly more bone, (4250.63 mm3, SD = 1485.57) than blank (1045.29 mm3, SD = 219.68) ECM-hydrogel (1152.58 mm3, SD = 191.95) and Stro-4+/ECM-hydrogel (1127.95 mm3, SD = 166.44) groups. Stro-4+ oBMSCs demonstrated a potential to aid bone repair in vitro and in a small in vivo bone defect model using select scaffolds. However, critically, translation to a large related preclinical model demonstrated the complexities of bringing small scale reported stem-cell material therapies to a clinically relevant model and thus facilitate progression to the clinic.
Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation
Authors: Fotios Karagiannis, Schekufe Kharabi Masouleh, Klaus Wunderling, Jayagopi Surendar, Vanessa Schmitt, Alexander Kazakov, Marcel Michla, Michael Hölzel, Christoph Thiele, Christoph Wilhelm
Journal: Immunity (2020)
Abstract 13960: Impact of Syntax Score on Release of Cardiac Biomarkers in Post-revascularization Procedures Among Patients With Stable Multivessel Disease: Mass-v Insights
Authors: Diogo F Azevedo, Whady Hueb, Myrthes E Takiuti, Eduardo G Lima, Paulo C Rezende, Cibele L Garzillo, Carlos A Segre, Jaime P Linhares Filho, Rosa M Garcia, Cesar H Nomura, Jose A Ramires, Roberto Kalil Filho
Journal: Circulation (2017)

Introduction: Abnormal cardiac enzymes release post-revascularization procedure has been associated with worse clinical outcomes.However, levels of myocardial biomarkers post revascularization proc...
Effective Radiation Doses for Lung Cancer Screening Scans
Authors: Adam Bernheim
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Eye care and ocular findings at the Olympic and Paralympic Games Rio 2016
Authors: Vagner Loduca Lima, Arthur Gustavo Fernandes, Rodrigo Galvão Viana, David Feder
Journal: British Journal of Sports Medicine (2020)

Objectives To describe the attendance and ocular profile of competitors and members of delegations who attended the Polyclinic Ophthalmology Division during the Olympic and Paralympic Games Rio 2016. Methods The eye clinic was allocated in the purpose-built polyclinic opened for competitors and members of delegations from 24 July to 18 September 2016. All individuals who attended the service received a comprehensive ocular examination including biomicroscopy, subjective refraction and fundus evaluation. A main clinical finding was assigned for each eye by the ophthalmologist. Results 5.6% of Olympic Games competitors and 8.9% of Paralympic Games competitors attended the Polyclinic Ophthalmology Division during the Rio Olympic and Paralympic Games. These rates compare with 2.6% and 6.5% at the London Olympic and Paralympic Games (2012). The main clinical finding was refractive error with 79.0% of the individuals receiving a glass prescription during the Olympic Games and 81.3% during the Paralympic Games. Conclusion Our outcomes highlight the importance of the eye service at the polyclinic as it may represent the only opportunity for many individuals involved with the Olympic and Paralympic Games to receive ocular evaluation. Our description of clinic structure, delivery of service and clinical results will be useful in the organisation not only for the Olympic and Paralympic Games Tokyo 2020 but also for any other large sporting events that involves medical attention in a polyclinic format.
Eltrombopag for Refractory Severe Aplastic Anemia: Dosing Regimens, Long-Term Follow-up, Clonal Evolution and Somatic Mutation Profiling
Authors: Thomas Winkler, James N. Cooper, Danielle M. Townsley, Phillip Scheinberg, Sophia Grasmeder, Colin Wu, Jennifer Lotter, Marie J Desierto, Ronan Desmond, Matthew J. Olnes, Katherine R Calvo, Neal S. Young, Cynthia E Dunbar
Journal: Blood (2017)
Substituting Angiotensin-(1-7) to Prevent Lung Damage in SARS-CoV-2 Infection?
Authors: Concepción Peiró, Salvador Moncada
Journal: Circulation (2020)

ike severe acute respiratory syndrome coronavirus (SARS-CoV), the new coronavirus SARS-CoV-2, which is causing the epidemic coronavirus disease 2019 , enters human cells by binding to angiotensin-converting enzyme-2 (ACE2) although with a higher affinity.1 Once attached to ACE2, the viral spike protein is primed by the host serine protease TMPRSS2, which ultimately allows fusion of viral and cellular membranes.ACE2 is a key protein of the protective branch of the renin-angiotensin system, which converts angiotensin (Ang) II, the main biologically active peptide of the RAS, into its physiological antagonist Ang-(1-7).ACE2 also metabolizes Ang I into Ang-(1-9), which is then converted into Ang-(1-7) by angiotensinconverting enzyme.Ang-(1-7) opposes the vasoconstrictor, proinflammatory, prooxidant, proproliferative, or profibrotic actions exerted by Ang II via AT1 receptors (Figure).The binding of SARS-CoV to ACE2 downregulates its expression, leading to increases in Ang II. 1 ACE2 is expressed in many organs, but is particularly abundant in alveolar epithelial cells and vascular endothelial cells. 2 This would explain why the lung is especially vulnerable to the new coronavirus.Indeed, the lethality of SARS-CoV has been shown to be dependent on the loss of key regulatory factors in the lung related to the downregulation of ACE2. 3 Ang-(1-7) seems to be critical in protecting against lung inflammation and fibrosis.This heptapeptide inhibits alveolar cell apoptosis, attenuates endothelial cell activation and the loss of barrier function and edema, and limits the synthesis of proinflammatory and profibrotic cytokines.This is particularly relevant because both acute lung injury and acute respiratory distress syndrome are accompanied by a cytokine storm and an overwhelming inflammatory response. 2Indeed, activated endothelial cells are increasingly recognized as main orchestrators of the inflammatory response in acute respiratory distress syndrome.Hypertension is a comorbidity that may exacerbate the severity of the new coronavirus infection. 4The underlying mechanisms are not clear, but the antihypertensive drugs such as AT1 receptor blockers or angiotensin-converting enzyme inhibitors increase ACE2 expression in animal models and humans.Because ACE2 is the receptor for the new coronavirus, it has been suggested that in patients treated with those drugs, the increase in the receptor may result in increased infection and therefore exacerbation of disease.Whether these treatments should be abandoned in favor of drugs neutral to ACE2, such as calcium channel blockers, is under discussion. 5However, there is at present no definitive evidence in humans in favor of this suggestion.On the other hand, the protective effect of ACE2 overexpression is better understood and has led to the contrasting hypothesis that using AT1 receptor blockers might protect against viral-induced lung injury.In a model of
Atrial Fibrillation
Authors: Mina K. Chung, Marwan Refaat, Win-Kuang Shen, Valentina Kutyifa, Yong-Mei Cha, Luigi Di Biase, Adrian Baranchuk, Rachel Lampert, Andrea Natale, John Fisher, Dhanunjaya R. Lakkireddy
Journal: Journal of the American College of Cardiology (2020)
The RESOLUTE consortium: unlocking SLC transporters for drug discovery
Authors: Giulio Superti-Furga, Daniel Lackner, Tabea Wiedmer, Alvaro Ingles-Prieto, Barbara Barbosa, Enrico Girardi, Ulrich Goldmann, Bettina Gürtl, Kristaps Klavins, Christoph Klimek, Sabrina Lindinger, Eva Liñeiro-Retes, André C. Müller, Svenja Onstein, Gregor Redinger, Daniela Reil, Vitaly Sedlyarov, Gernot Wolf, Matthew Crawford, Robert Everley, David Hepworth, Shenping Liu, Stephen Noell, Mary Piotrowski, Robert Stanton, Hui Zhang, Salvatore Corallino, Andrea Faedo, Maria Insidioso, Giovanna Maresca, Loredana Redaelli, Francesca Sassone, Lia Scarabottolo, Michela Stucchi, Paola Tarroni, Sara Tremolada, Helena Batoulis, Andreas Becker, Eckhard Bender, Yung-Ning Chang, Alexander Ehrmann, Anke Müller-Fahrnow, Vera Pütter, Diana Zindel, Bradford Hamilton, Martin Lenter, Diana Santacruz, Coralie Viollet, Charles Whitehurst, Kai Johnsson, Philipp Leippe, Birgit Baumgarten, Lena Chang, Yvonne Ibig, Martin Pfeifer, Jürgen Reinhardt, Julian Schönbett, Paul Selzer, Klaus Seuwen, Charles Bettembourg, Bruno Biton, Jörg Czech, Hélène de Foucauld, Michel Didier, Thomas Licher, Vincent Mikol, Antje Pommereau, Frédéric Puech, Veeranagouda Yaligara, Aled Edwards, Brandon J. Bongers, Laura H. Heitman, Ad P. IJzerman, Huub J. Sijben, Gerard J.P. van Westen, Justine Grixti, Douglas B. Kell, Farah Mughal, Neil Swainston, Marina Wright-Muelas, Tina Bohstedt, Nicola Burgess-Brown, Liz Carpenter, Katharina Dürr, Jesper Hansen, Andreea Scacioc, Giulia Banci, Claire Colas, Daniela Digles, Gerhard Ecker, Barbara Füzi, Viktoria Gamsjäger, Melanie Grandits, Riccardo Martini, Florentina Troger, Patrick Altermatt, Cédric Doucerain, Franz Dürrenberger, Vania Manolova, Anna-Lena Steck, Hanna Sundström, Maria Wilhelm, Claire M. Steppan
Journal: Nature Reviews Drug Discovery (2020)
Transcutaneous DNA immunization of Human Papilloma Virus-16 E7 with hair-follicle specific promoter in mice
Authors: Chan Kim
Journal: Cancer Research (2008)

2838  Backgrounds and Aims : Previous reports have shown that transcutaneous immunization (TCI) with proteins or peptides in combination with adjuvants efficiently induces specific cellular and humoral immune responses. We compared the immune response after TCI with new construct which was derived from HPV-16 E7opt+K and pK6hf promoter instead of pCMV promoter and various adjuvant.  Methods : First, we made new construct ligated with HPV-16 E7 opt+K to Hair-follicle Specific pK6hf Promoter. Second, we applied pk6hf-E7 opt + K DNA with or without Lipofectamine 2000 and a combination of cholera toxin (CT) and CpG oligodeoxynucleotide (CpG) onto cold wax-depilated and hydrated bare skin of C57 BL/6 mice. To assess the ability of CTL(cytotoxic T-lymphocyte) activity, we performed intracellular cytokine staining with flow cytometric analysis to determine the number of E7-specific IFN-gamma- secreting CD8+ T cells generated in vaccinated mice with the DNA vaccine.  Results : Female C57BL/6 mice immunized by TCI methods with 30 microgram of pk6hf-E7 opt+K DNA with Lipofectamine2000 and CT efficiently generated E7-specific CD8(+) T cells compared with the group of pk6hf-E7 opt+K DNA only or DNA with Lipofectamine2000.  Conclusions : Our results demonstrate that TCI of the linkaged-E7 DNA , E7 opt+K DNA to pk6hf, and Lipofectamine2000 and CT induced an antigen-specific CTL response. This result is of potential relevance for the development of therapeutic HPV-specific DNA vaccines with TCI and pK6hf promoter can be used safely.
Covid-19 in South Korea — Challenges of Subclinical Manifestations
Authors: Joon-Young Song, Jin-Gu Yun, Ji-Yun Noh, Hee-Jin Cheong, Woo-Joo Kim
Journal: New England Journal of Medicine (2020)

Subclinical Covid-19 in South Korea Among 28 early confirmed cases of Covid-19 in South Korea, diagnosis was delayed in 11 patients because of subclinical symptoms and diverse initial manifestation...
Impact of Provider Imaging Practices on Survival Outcomes in Advanced Ovarian Cancer
Authors: Angela K. Green, Deborah Korenstein, Carol Aghajanian, Brooke Barrow, Michael Curry, Roisin E. O’Cearbhaill
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: This study sought to describe how high- versus low-frequency surveillance imaging practices among providers at Memorial Sloan Kettering Cancer Center (MSKCC) impact overall survival (OS) and time to recurrence of patients with advanced epithelial ovarian cancer in first remission. Methods: The study cohort included patients with stage II–IV high-grade epithelial ovarian cancer diagnosed in January 2001 through January 2017 who experienced recurrence after initial platinum-based chemotherapy. To determine usual imaging practices for providers at MSKCC, median frequency of CT or MRI of the abdomen/pelvis was calculated among patients with a long-term remission (defined as at least 1 year) treated by each provider. Cox proportional hazards models were used to examine differences in OS and time to recurrence among patients treated by providers with high versus low imaging frequency practices, with additional subgroup analysis among patients with elevated CA-125 levels >35 U/mL at diagnosis. Chi-square tests were used to examine differences in the proportion of patients who enrolled in clinical trials or underwent secondary cytoreductive surgery (SCS) by imaging frequency. Results: A total of 543 patients were treated by providers with high imaging frequency (>1 scan every 12 months) and 141 were treated by providers with low imaging frequency (≤1 scan every 12 months). Time to recurrence was shorter among patients treated by providers with high versus low imaging frequency (18.0 vs 19.2 months; hazard ratio, 1.33; P=.003). Results were similar when restricted to patients with elevated CA-125 levels at diagnosis. There was no significant difference in OS, clinical trial enrollment, or SCS by imaging practice. Conclusions: Within the limitations of this retrospective analysis, patients with advanced ovarian cancer treated by high-frequency-imaging providers had earlier detection of recurrence. Future analyses in a larger population are warranted to elucidate the risks versus benefits of surveillance imaging.
Regional Structure-Function in Cystic Fibrosis Lung Disease Using Hyperpolarized <sup>129</sup>Xe and Ultrashort Echo Magnetic Resonance Imaging
Authors: Robert P. Thomen, Laura L. Walkup, David J. Roach, Nara Higano, Andrew Schapiro, Alan Brody, John P. Clancy, Zackary I. Cleveland, Jason C. Woods
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
FDA Trials Find Sunscreen Ingredients in Blood, but Risk Is Uncertain
Authors: Jennifer Abbasi
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ovarian carcinoma spheroids demonstrate an invasive potential
Authors: Kathryn M. Burleson, Amy P. Skubitz
Journal: Cancer Research (2004)

4917  Ovarian carcinoma patients frequently develop a malignant peritoneal ascites fluid containing single and aggregated tumor cells, or spheroids. Spheroids have been used as models of tumor microenvironments, and have been shown to be resistant to many therapies, but their potential to contribute to ovarian cancer dissemination has not been determined. We have previously shown that spheroids recovered from eleven stage III ovarian carcinoma patients could adhere to laminin, fibronectin, type I collagen, and type IV collagen, partially through β1 integrin subunit interactions. Patient ascites spheroids also adhered to live mesothelial cell monolayers via β1 integrin subunits. In the present study, we assessed the ability of spheroids to disseminate and invade in vitro. To determine their ability to disaggregate, spheroids generated from the human ovarian carcinoma cell line NIH:OVCAR5 were placed on a variety of extracellular matrix components for 24 hours. While laminin, fibronectin, and type IV collagen stimulated minor cell migration out of the spheroid, type I collagen caused complete spheroid disaggregation. A blocking antibody against the β1 integrin subunit significantly inhibited outgrowth on all extracellular matrix components. We next tested the ability of NIH:OVCAR5 spheroids to invade human mesothelial cells monolayers. NIH:OVCAR5 spheroids were added to confluent monolayers of live or methanol-fixed human LP9 mesothelial cells. Within 24 hours, the NIH:OVCAR5 spheroids adhered and disseminated on the mesothelial cell monolayers, and rapidly established foci of invasion, resulting in a 200-fold change in surface area within a week. Addition of a blocking antibody against the β1 integrin subunit almost completely inhibited NIH:OVCAR5 spheroid invasion into live and fixed mesothelial monolayers. To assess the contribution of proteases to this invasion, GM 6001, a broad-scale matrix metalloproteinase inhibitor, was added to the assays. The addition of GM 6001 caused nearly complete inhibition of spheroid invasion into live mesothelial monolayers, and reduced invasion into fixed mesothelial cell monolayers by about 70%. Addition of e-amino-N-caproic acid, a serine protease inhibitor, reduced NIH:OVCAR5 spheroid invasion into live monolayers by about 30%, and reduced invasion into fixed monolayers by about 50%. Interestingly, while both of the protease inhibitors significantly blocked spheroid cell invasion into the monolayers, considerable cell attachment and migration on top of the fixed monolayers still occurred. In summary, ovarian carcinoma spheroids demonstrate the ability to attach to and invade mesothelial cell monolayers via β1 integrin subunit interactions and by the production of proteases. Thus, spheroids should be regarded as a potential source of dissemination in ovarian cancer.