tbuckley/cabot-search huggingface dataset:
David Oliver: The medical examiner role could transform our approach to handling death
Authors: David Oliver
Journal: BMJ (2020)

In April 2019 NHS Improvement announced a national programme to introduce a new medical examiner role at all acute hospital trusts in England, to provide independent scrutiny of all deaths.12 Wales is adopting a similar approach.3 I can see potential for this initiative to transform the way doctors and hospitals handle and learn from death and to drive improvements in care and the experiences of bereaved people.

The current pandemic has brought temporary modifications under the emergency Coronavirus Act and covid-19 specific guidance regarding certification and notification of deaths.4 Covid-19 has highlighted the vital importance of accurate, scrutinised death certification.5

Under the new initiative, each acute trust should establish …
Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after study
Authors: Refeletswe Lebelonyane, Pamela Bachanas, Lisa Block, Faith Ussery, William Abrams, Michelle Roland, Joe Theu, Max Kapanda, Stembile Matambo, Shahin Lockman, Tendani Gaolathe, Joseph Makhema, Janet Moore, Joseph N Jarvis
Journal: The Lancet HIV (2020)
Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma
Authors: Paul D. Harker-Murray, Lauren Pommert, Matthew J. Barth
Journal: Journal of the National Comprehensive Cancer Network (2020)

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody-drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody-drug conjugates are in development. Additionally, bispecific T-cell-engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell-mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.
Clinical metagenomic sequencing for diagnosis of pulmonary tuberculosis
Authors: Cui-Lin Shi, Peng Han, Pei-Jun Tang, Meng-Meng Chen, Zhi-Jian Ye, Mei-Ying Wu, Jie Shen, Hai-Yan Wu, Zhu-Qing Tan, Xin Yu, Guan-Hua Rao, Jian-Ping Zhang
Journal: Journal of Infection (2020)
Hematopoietic Progenitor Cell Transplantation in Children, Adolescents, and Young Adults With Relapsed Mature B-Cell NHL
Authors: Aliza Gardenswartz, Mitchell S. Cairo
Journal: Journal of the National Comprehensive Cancer Network (2020)

Although children, adolescents, and young adults with newly diagnosed B-cell non-Hodgkin’s lymphoma enjoy excellent overall survival with current chemoimmunotherapy, those with relapsed and/or refractory disease have a dismal prognosis. Although most clinicians would agree that hematopoietic progenitor cell transplantation after reinduction therapy is frontline therapy for these patients, there is no consensus as to what type of hematopoietic progenitor cell transplantation promises the best event-free and overall survival. This review outlines the disparate types of stem cell therapy that have been used in this difficult-to-treat population as well as the role of maintenance and CAR T-cell therapy in conjunction with stem cell therapy.
Abstract 10886: Frailty Assessment and Short-term Prognosis in Elderly Hospitalized Patients With Cardiovascular Disease
Authors: Yaodan Liang, Hua Wang, Kefan Fu, Ning Sun, Simin Yao, Peipei Zheng, Yuhao Wan, Jiefu Yang
Journal: Circulation (2019)

Aims: To investigate the impact of frailty on short-term outcomes in elderly hospitalized patients with cardiovascular disease, using the frailty phenotype, clinical frailty scale (CFS), and the Fr...
Partha Kar: Our approach to tackling obesity needs rethinking
Authors: Partha Kar
Journal: BMJ (2020)

Obesity is a focus of political and media discussion, since multiple datasets have shown that being overweight puts people at greater risk of serious illness from covid-19. But, if we want to improve the way we manage obesity, we need better research on what works in weight management—and a rethink of our approach to service provision.

NICE’s most recent guidance on identifying, assessing, and managing obesity was published in 20141: in the six years since, has there been no new evidence that would warrant an update? At that time, a lot of NICE’s recommendations were based on thin evidence, and NICE clearly accepted in its guidance that there were gaps in the research that needed covering. So, why hasn’t the research community or …
Loop Diuretic Prescription and 30-Day Outcomes in Older Patients With Heart Failure
Authors: Charles Faselis, Cherinne Arundel, Samir Patel, Phillip H Lam, Stephen S Gottlieb, Michael R Zile, Prakash Deedwania, Gerasimos Filippatos, Helen M Sheriff, Qing Zeng, Charity J Morgan, Samuel Wopperer, Tran Nguyen, Richard M Allman, Gregg C Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2020)
Comprehensive Genomic Characterization of Refractory Multiple Myeloma Reveals a Complex Mutational and Structural Landscape Associated with Drug Resistance
Authors: Nicola Lehners, Umut H Toprak, Jing Xu, Nagarajan Paramasivam, Daniel Hübschmann, Martina Fröhlich, Nur H Md Hanafiah, Sadaf Mughal, Elias K Mai, Anna Jauch, Jens Hillengass, Roland Eils, Carsten Müller-Tidow, Benedikt Brors, Hartmut Goldschmidt, Matthias Schlesner, Marc S Raab
Journal: Blood (2017)
Response to: ‘Women’s journey in Mexican rheumatology. Comment on ‘Gender gap in rheumatology: speaker representation at annual conferences’ by Monga<i>et al</i>’ by Colunga-Pedraza<i>et al</i>
Authors: Kanika Monga, Jean Liew
Journal: Annals of the Rheumatic Diseases (2020)

We read the correspondence by Colunga-Pedraza et al to our letter about the gender gap in the American College of Rheumatology (ACR) annual conference with great interest. 1 2 The authors provide data on the first authors of oral presentations in the Mexican College of Rheumatology (MCR) annual meetings from 2011 to 2018.Out of 153 oral presentations, 79 (51.6%) had women as first authors.While the overall percentage of oral presentations given by female authors surpassed the 42.1% reported as the total number of female rheumatologists in Mexico up to 2017, they found that there were fluctuations based on the year.If the data were available, an additionally valuable insight would be whether these fluctuations were correlated with the proportion of women among new rheumatologists entering the workforce in those years.We have previously commented on the value of looking at both first and senior authors when responding to the work of Adami et al. 1 3 The representation of women among the first authors of original research in high impact general medical journals was significantly higher overall in 2014 compared with 1994, in a study by Filardo et al. 4 These authors also noted differences in gender representation that varied across journals, as well as plateauing or declining trends in some cases.An older study by Jagsi et al evaluated the percentage of both first and senior authors in high-impact medical journals 5 and found significantly increases over time for both.Looking at both authorship positions, whether it is for oral abstract presentations or publications, would provide some information on trends over time, as the last authorship position is usually reserved for a more senior researcher.It would also be helpful to note whether the selection process for these abstracts involves a double-blind peer review, as this tends to favour increased representation of female authors. 6 7 In summary, Colunga-Pedraza et al present more data to support improved gender representation in rheumatology-but also the fact that we still have improvements left to make.
Abstract B34: Cord blood CD34+ HSPCs: An in vitro model system for characterizing NUP98 fusions
Authors: Ryan Hiltenbrand, Jonathan Miller, Jeffery Klco
Journal: Cancer Research (2020)

Abstract Chromosomal translocations of the Nucleoporin 98 gene (NUP98) are associated with multiple hematopoietic malignancies. In particular, NUP98 rearrangements can be found in up to 6.6% of de novo cases of pediatric AML. Specific subpopulations of pediatric AML appear to be even more enriched for NUP98 fusions, with over 16% of cytogenetically normal pediatric AML patients and 15% of non-Down syndrome acute megakaryoblastic leukemia (AMKL) patients harboring these fusions. Clinically, the NUP98-KDM5A fusion is associated with erythroid and megakaryocytic leukemias while the NUP98-NSD1 fusion is associated with myelomonocytic leukemias. When NUP98 fusions are present in AML, they confer a poor prognosis. To better characterize the role of these fusions in human hematopoiesis, we used cord blood CD34+ (cb-CD34+) hematopoietic stem and progenitor cells (HSPCs) as an in vitro model system. We transduced cb-CD34+ HSPCs with NUP98-NSD1, NUP98-KDM5A, or empty vector control and studied the effects on cell proliferation and differentiation in liquid culture media containing cytokines (IL-6, FLT3-Ligand, SCF, TPO, and SR1 (an aryl hydrocarbon receptor antagonist)). NUP98-NSD1 and NUP98-KDM5A fusions increase the proliferation rate in liquid culture by three-fold and 19-fold, respectively (p&amp;lt;0.05). Consistent with observations from patients with these fusions, cells expressing NUP98-KDM5A have increased expression of CD235A and CD71, consistent with erythroid differentiation (p&amp;lt;0.05). In addition, cells expressing NUP98-NSD1 have increased expression of CD11b compared to NUP98-KDM5A (p&amp;lt;0.01) expressing cells. When placed in methylcellulose, the NUP98 fusions tested had no effect on total colony number, but we observed more erythroid differentiation for NUP98-KDM5A compared to vector control (p&amp;lt;0.05). Overall, the results of these in vitro studies demonstrate increased proliferation and inhibition of differentiation in HSPCs by NUP98 fusions, and cell differentiation patterns parallel the different AML subtypes observed in patients with NUP98-NSD1 and NUP98-KDM5A fusions. We propose cbCD34+ HSPCs as a promising system for in vitro modeling of NUP98 fusions. Citation Format: Ryan Hiltenbrand, Jonathan Miller, Jeffery Klco. Cord blood CD34+ HSPCs: An in vitro model system for characterizing NUP98 fusions [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B34.
Uberization of Prehospital Communications—Are We Ready?
Authors: Stephen R. Dowker, Brahmajee K. Nallamothu
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Abstract A15: Improving immune recognition of shared tumor-associated antigens in pediatric tumors using a multimodal oncolytic virus
Authors: Mohammed G. Ghonime, Justin C. Roth, Naomi J. Barker, Katherine E. Miller, Elaine R. Mardis, Christopher M. Walker, Kevin A. Cassady
Journal: Cancer Research (2020)

Abstract Immunotherapy is an attractive treatment approach for children because of its precision and reduced toxicity. Unfortunately, pediatric solid tumors often evade immune recognition. Like adult cancers, the immunosuppressive tumor microenvironment can restrict immune activity. Further complicating this, pediatric cancers have low mutation rates, creating fewer antigenic targets for the immune response. We therefore developed a multimodal oncolytic virus that harnesses the antiviral immune response and redirects it against shared tumor-associated antigen (TAA) in the tumor. Engineering a TAA, Ephrin A2 (EphA2), into the oncoviral (OV) genome circumvents transcriptional/translational arrest and allows TAA overexpression during infection. Our results show that virus-based EphA2 expression (C57BL/6 sequence) induces an immune-mediated antitumor response in syngeneic C57BL/6-based brain and peripheral tumor models, improving survival (e.g., CT2A brain tumor median survival: 43d-TAA virus vs. 30d-parent virus, 29d-Saline; overall survival: 44.4%-TAA virus vs. 12%-parent virus vs 0%-Saline, *p=0.0233). TAA-virus treatment increases CD8 memory effector-like cells in tumor infiltrates (CD62L+, CD44+) and rechallenge studies show abscopal effect in TAA-virus treated survivors. Peptide pulsing studies using splenocytes from survivors show that viral TAA expression induces a circulating EphA2-specific CD8 effector-like (CD8+, CD25+, Granzyme B+) population (14.1%-TAA virus vs 2.6%-parent virus, 0.6% Saline, **p≤0.0098). This multimodal viral platform harnesses the oncolytic and immunostimulatory properties of a next-generation OV to enhance immune activity against tumors expressing shared tumor antigens. Our results suggest that this flexible viral-based platform provides an effective in situ antitumor vaccination approach and could be engineered against multiple antigens for low mutational load tumors. Citation Format: Mohammed G. Ghonime, Justin C. Roth, Naomi J. Barker, Katherine E. Miller, Elaine R. Mardis, Christopher M. Walker, Kevin A. Cassady. Improving immune recognition of shared tumor-associated antigens in pediatric tumors using a multimodal oncolytic virus [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A15.
Delayed virus‐specific antibody responses associate with COVID‐19 mortality
Authors: Feng Wang, Yin Yao, Hongyan Hou, Shiji Wu, Cuilian Guo, Hongmin Zhou, Zheng Liu, Ziyong Sun
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
Authors: Sandeep R. Das, Brendan M. Everett, Kim K. Birtcher, Jenifer M. Brown, James L. Januzzi, Rita R. Kalyani, Mikhail Kosiborod, Melissa Magwire, Pamela B. Morris, Joshua J. Neumiller, Laurence S. Sperling
Journal: Journal of the American College of Cardiology (2020)
Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix
Authors: Honglin Jiang, Robert J. Torphy, Katja Steiger, Henry Hongo, Alexa J. Ritchie, Mark Kriegsmann, David Horst, Sarah E. Umetsu, Nancy M. Joseph, Kimberly McGregor, Michael J. Pishvaian, Edik M. Blais, Brian Lu, Mingyu Li, Michael Hollingsworth, Connor Stashko, Keith Volmar, Jen Jen Yeh, Valerie M. Weaver, Zhen J. Wang, Margaret A. Tempero, Wilko Weichert, Eric A. Collisson
Journal: Journal of Clinical Investigation (2020)

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti–lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.
Abstract #1847: Inhibitors of histone deacetylase, valproic acid and trichostatin A, increase cytotoxicity of anticancer drug ellipticine to neuroblastoma cells
Authors: Jan Hrabeta, Jitka Poljakova, Eva Frei, Marie Stiborova, Tomas Eckschlager
Journal: Cancer Research (2009)

Ellipticine exhibits antitumor activity. The mechanisms of ellipticine action are based on DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts mediated by cytochromes P450 and peroxidases. The aim of our study was to evaluate the cytotoxicity of ellipticine to human neuroblastoma lines IMR-32, UKF-NB-3, UKF-NB-4 and UKF-NB-4ELLI (cell line possessing resistance to ellipticine). Furthermore, the effect of histone deacetylases inhibitors (HDACi) valproic acid (VPA) and trichostatin A (TSA)on the ellipticine cytotoxicity was also examined. The IC50 values were determined by MTT test. Ellipticine adducts were detected using the 32P-postlabeling assay. The highest toxicity of ellipticine was detected to IMR-32 cells (IC50 = 0.26 \#956;M), followed by the toxicity to UKF-NB-3 and UKF-NB-4 cells, with the IC50 values of 0.80 and 1.26 \#956;M ellipticine, respectively. IC50 ofUKF-NB-4ELLI was 9.5 \#956;M . DNA adducts were generated by ellipticine in neuroblastoma cells. Two of them were identical with those formed by ellipticine metabolites 13-hydroxy- and 12-hydroxyellipticine with deoxyguanosine in DNA. Total levels of DNA adducts generated by 10 \#956;M ellipticine in neuroblastoma cells differ significantly, being highest in IMR-32 cells (26 adducts/107 nucleotides), while 8 and 17 adducts/107 nucleotides were formed in UKF-NB-3 and UKF-NB-4 cells, respectively. The pre-treatment of neuroblastoma cell lines with HDACi increase the cytotoxicity of ellipticine. The higher efficiency of ellipticine to neuroblastoma cells produced by their pre-treatment with HDACi correlated with an increase in adduct formation. Ellipticine is toxic to neuroblastoma. Its effect is increased by pre-treatment with HDACi. We suggest that the formation of covalent DNA adducts by ellipticine is one of the most important mechanisms of ellipticine action to neuroblastoma.Our results show that ellipticine is effective on neuroblastoma cells and its effect may be potentiate by HDACi. Supported by grants GACR 203/06/0329, IGA NR9522-3/2007 and MSM0021620813.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1847.
Annals Graphic Medicine - More Than MD
Authors: Annie Zhu, Arnav Agarwal
Journal: Annals of Internal Medicine (2020)

Web Exclusives4 August 2020Annals Graphic Medicine - More Than MDFREEAnnie Zhu, BHSc and Arnav Agarwal, MDAnnie Zhu, BHScUniversity of Toronto, Toronto, Ontario, Canada (A.Z., A.A.)Search for more papers by this author and Arnav Agarwal, MDUniversity of Toronto, Toronto, Ontario, Canada (A.Z., A.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0090 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto, Toronto, Ontario, Canada (A.Z., A.A.)Disclosures: The authors have disclosed no conflicts of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0090.Author/Illustrator Information: Annie Zhu is a medical student at the University of Toronto. She is interested in sequential art and exploring narratives in medicine. Her other illustrations and comics can be found at cazezhu.carbonmade.com. Dr. Arnav Agarwal is an internal medicine resident at the University of Toronto. He is passionate about clinical epidemiology research, health advocacy and allyship, and medical curriculum development and has a deep appreciation for art and narrative writing as media for reflection and advocacy. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 August 2020Volume 173, Issue 3Page: W57-W58KeywordsClinical epidemiologyConflicts of interestDisclosureHealth care ePublished: 4 August 2020 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...