tbuckley/cabot-search huggingface dataset:
It's Time to Revise the Uniform Determination of Death Act
Authors: Edward J. Kasarskis, Larry B. Goldstein
Journal: Annals of Internal Medicine (2020)

Letters7 July 2020It's Time to Revise the Uniform Determination of Death ActEdward J. Kasarskis, MD, PhD and Larry B. Goldstein, MDEdward J. Kasarskis, MD, PhDUniversity of Kentucky, Lexington, Kentucky (E.J.K., L.B.G.)Search for more papers by this author and Larry B. Goldstein, MDUniversity of Kentucky, Lexington, Kentucky (E.J.K., L.B.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0256 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read Lewis and colleagues' commentary (1) with interest. When a person has a catastrophic neurologic event compromising their decision-making capacity, their legal representatives are required to confront multiple weighty existential issues. This is the case when they face discussions with health care providers related to the process of determining brain death.Lewis and colleagues discuss the confusion that results from a lack of uniformity in the definition of “acceptable medical standards” for the determination of brain death and call for a revision of the Uniform Determination of Death Act to address this shortcoming (1). We agree ...References1. Lewis A, Bonnie RJ, Pope T. It's time to revise the Uniform Determination of Death Act. Ann Intern Med. 2020;172:143-144. [PMID: 31869833]. doi:10.7326/M19-2731 LinkGoogle Scholar2. Wijdicks EF, Varelas PN, Gronseth GS, et al; American Academy of Neurology.. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911-1918. [PMID: 20530327] doi:10.1212/WNL.0b013e3181e242a8 CrossrefMedlineGoogle Scholar3. United Nations Office on Drugs and Crime. Understanding the Synthetic Drug Market: The NPS Factor. Global SMART Update. United Nations Office on Drugs and Crime; March 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Kentucky, Lexington, Kentucky (E.J.K., L.B.G.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0256. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIt's Time to Revise the Uniform Determination of Death Act Ariane Lewis , Richard J. Bonnie , and Thaddeus Pope It's Time to Revise the Uniform Determination of Death Act Ariane Lewis , Richard J. Bonnie , and Thaddeus Pope Metrics 7 July 2020Volume 173, Issue 1Page: 75KeywordsBrainBrain damageClinical laboratoriesComaDrug screeningDrug synthesisDrugsPatient advocacyToxicologyUrine ePublished: 7 July 2020 Issue Published: 7 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dissecting the Important Difference Between Good Surgeons and Good Leaders
Authors: Michael Tarnoff
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Recent advances in CAR-T cell engineering
Authors: Ruihao Huang, Xiaoping Li, Yundi He, Wen Zhu, Lei Gao, Yao Liu, Li Gao, Qin Wen, Jiang F. Zhong, Cheng Zhang, Xi Zhang
Journal: Journal of Hematology & Oncology (2020)

Abstract Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CAR-T therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CAR-T cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CAR-T cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CAR-T cells. Paired with an immune modifier, the use of fourth-generation and next-generation CAR-T cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CAR-T cell therapy.
When the Smoke Clears m6A from a Y Chromosome–Linked lncRNA, Men Get an Increased Risk of Cancer
Authors: A. Rouf Banday, Brenen W. Papenberg, Ludmila Prokunina-Olsson
Journal: Cancer Research (2020)

Abstract Long noncoding RNAs (lncRNA) have been implicated in many diseases, including cancer. Although these disease-associated effects have been mostly attributed to the ability of lncRNAs to function as regulatory noncoding transcripts, there is growing evidence that lncRNAs may also encode functional micropeptides. In the current issue of Cancer Research, Wu and colleagues report a micropeptide encoded by a Y chromosome–linked lncRNA that may explain the higher incidence of esophageal cancer in male smokers. Furthermore, this report provides broader insights related to the molecular epidemiology of male-dominant and smoking-driven cancers and may also help explain some cancer-related associations with mosaic Y chromosome loss. See related article by Wu et al., p. 2790
Optimal management of large proximal ureteral stones (&gt;10 mm): A systematic review and meta-analysis of 12 randomized controlled trials
Authors: Shicong Lai, Binbin Jiao, Tongxiang Diao, Samuel Seery, Maolin Hu, Miao Wang, Huimin Hou, Jianye Wang, Guan Zhang, Ming Liu
Journal: International Journal of Surgery (2020)
Most chilblains observed during the COVID‐19 outbreak occur in patients who are negative for COVID‐19 on polymerase chain reaction and serology testing*
Authors: L. Le Cleach, L. Dousset, H. Assier, S. Fourati, S. Barbarot, C. Boulard, C. Bourseau Quetier, L. Cambon, C Cazanave, A. Colin, E. Kostrzewa, C. Lesort, A. Levy Roy, F. Lombart, J. Marco‐Bonnet, J.‐B. Monfort, M. Samimi, M. Tardieu, P. Wolkenstein, E. Sbidian, M. Beylot‐Barry
Journal: British Journal of Dermatology (2020)

Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed.
Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors
Authors: Eolia Brissot, Myriam Labopin, Ian Moiseev, J. J. Cornelissen, Ellen Meijer, Gwendolyn Van Gorkom, Montserrat Rovira, Fabio Ciceri, Laimonas Griskevicius, Didier Blaise, Edouard Forcade, Martin Mistrik, Stephan Mielke, Claude Eric Bulabois, Riitta Niittyvuopio, Eric Deconinck, Annalisa Ruggeri, Jaime Sanz, Alexandros Spyridonidis, Bipin Savani, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II–IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.
First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors
Authors: Robert McLeod, Rajiv Kumar, Dionysis Papadatos-Pastos, Joaquin Mateo, Jessica S. Brown, Alvaro H. Ingles Garces, Ruth Ruddle, Shaun Decordova, Simone Jueliger, Roberta Ferraldeschi, Oscar Maiques, Victoria Sanz-Moreno, Paul Jones, Stephanie Traub, Gavin Halbert, Sarah Mellor, Karen E. Swales, Florence I. Raynaud, Michelle D. Garrett, Udai Banerji
Journal: Clinical Cancer Research (2020)

AT13148 is an oral AGC kinase inhibitor, which potently inhibits ROCK and AKT kinases. In preclinical models, AT13148 has been shown to have antimetastatic and antiproliferative activity.
Whole-Body 177Lu–Prostate-Specific Membrane Antigen Scan Pattern With Excess Free 177Lu-Chloride in a Metastatic Castration-Resistant Prostate Cancer Patient
Authors: Emran Askari, Soroush Zarehparvar Moghadam, Ghasemali Divband, Kamran Aryana
Journal: Clinical Nuclear Medicine (2020)

Abstract A 56-year-old man with metastatic castration-resistant prostate cancer was referred for radioligand therapy with 177 Lu–prostate-specific membrane antigen. In the third cycle, a posttherapy whole-body scan showed unexpected skeletal and joint uptake apart from his known metastatic lesions. This observation raised suspicion for possible impurity (mainly free lutetium) in the applied radiopharmaceutical product. After contacting the radiopharmaceutical company, we were informed that the radiochemical purity of the used batch of 177 Lu–prostate-specific membrane antigen had been 95%. This is the first report of excess free lutetium scan pattern and its complications in a patient undergoing radioligand therapy.
Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes
Authors: Qian Yang, Jijia Hu, Yingjie Yang, Zhaowei Chen, Jun Feng, Zijing Zhu, Huiming Wang, Dingping Yang, Wei Liang, Guohua Ding
Journal: Theranostics (2020)

Disturbed renal lipid metabolism, especially cholesterol dysregulation plays a crucial role in the pathogenesis of chronic kidney disease (CKD).We recently reported that angiotensin (Ang) II could induce cholesterol accumulation and injury in podocytes.However, the underlying mechanisms for these alterations remain unknown.Methods: Bioinformatics analysis of renal biopsy specimens from patients with hypertensive nephropathy (HN) suggests the involvement of Sirtuin 6 (Sirt6) in Ang II-induced dysregulation of glomerular cholesterol.Using a podocyte-specific Sirt6 knockout mouse model, the effects of Sirt6 on Ang II-induced cholesterol accumulation in podocytes and the therapeutic efficacies of cholesterol-lowering agents were evaluated.Results: Cholesterol accumulation was detected in the podocytes of Ang II-infused mice, whereas selective deletion of Sirt6 in podocytes not only increased cholesterol accumulation in these cells but also exacerbated Ang II-induced kidney injury.Deletion of Sirt6 also attenuated the protective effect of cyclodextrin (CD) on Ang II-induced urinary albumin excretion, glomerulosclerosis and podocyte injury.In addition, we demonstrated that Sirt6 affected cholesterol efflux in podocytes by regulating the expression of ATP-binding cassette transporter G1 (ABCG1).Conclusions: These findings provide evidence that Sirt6 is a potential target for renin-angiotensin system (RAS)-associated podocyte injury and provide a rationale for the application of cholesterol-lowering agents in patients with CKD.
Long-Term Outcome in Children and Adolescents with Chronic Myeloid Leukemia in Chronic Phase Treated with High-Dose Imatinib— the Italian Experience
Authors: Fiorina Giona, Michelina Santopietro, Giuseppe Menna, Concetta Micalizzi, Maria Caterina Putti, Nicola Santoro, Ottavio Ziino, Rosamaria Mura, Saverio Ladogana, Grazia Iaria, Antonella Sau, Roberta Burnelli, Nadia Vacca, Margherita Nardi, Caterina Consarino, Eleonora Miulli, Maria Luisa Moleti, Fara Petruzziello, Sonia Maria Orlando, Andrea Biondi, Franco Locatelli, Giuseppe Saglio, Robin Foa
Journal: Blood (2017)
Response to: ‘Comparison of MS score and HScore for the diagnosis of adult-onset Still’s disease associated macrophage activation syndrome’ by Zhang<i>et al</i>
Authors: Francesca Minoia, Angelo Ravelli
Journal: Annals of the Rheumatic Diseases (2020)

We thank Zhang et al 1 for their interest in our MAS/sJIA (MS) score for diagnosis of macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA).2 Considering that sJIA and adult-onset Still’s disease (AOSD) are nowadays thought to constitute a continuum of a single disease entity3 4 and that they share a similar risk for MAS, it is worth evaluating whether the proposed diagnostic tools are suitable to detect MAS in both illnesses.

Zhang et al 1 compared the diagnostic performance of the MS score with that of the HScore5 in their retrospective series of 209 patients with AOSD, 35 of whom had MAS. The HScore is aimed at identifying a broad range of reactive haemophagocytic syndromes and has been developed in a cohort …
The Fire Within: NF-κB Involvement in Non–Small Cell Lung Cancer
Authors: Foteinos-Ioannis D. Dimitrakopoulos, Anastasia E. Kottorou, Melpomeni Kalofonou, Haralabos P. Kalofonos
Journal: Cancer Research (2020)

Thirty-four years since its discovery, NF-κB remains a transcription factor with great potential for cancer therapy. However, NF-κB-targeted therapies have yet to find a way to be clinically translatable. Here, we focus exclusively on the role of NF-κB in non-small cell lung cancer (NSCLC) and discuss its contributing effect on cancer hallmarks such as inflammation, proliferation, survival, apoptosis, angiogenesis, epithelial-mesenchymal transition, metastasis, stemness, metabolism, and therapy resistance. In addition, we present our current knowledge of the clinical significance of NF-κB and its involvement in the treatment of patients with NSCLC with chemotherapy, targeted therapies, and immunotherapy.
Face masks for the public during covid-19: the more things change
Authors: Annemarie Jutel
Journal: BMJ (2020)

On 1 November 1918, Stars and Stripes (the official newspaper of the American Expeditionary Forces) proudly announced: “Gauze masks for men on transport keep flu at bay.”1 Some 5000 men crossed the North Atlantic Ocean wearing masks fashioned from squares of gauze “saturated with a 1% solution of iodine” and fastened with strips of adhesive. There were “no missing men when …
Abstract IA15: Modeling the tumor microenvironment of high-grade serous ovarian cancer
Authors: Frances Balkwill
Journal: Clinical Cancer Research (2020)

Abstract Using biopsies of metastatic high-grade serous ovarian cancer (HGSOC) that ranged from minimal to extensive disease, we defined RNA and protein profiles that evolved with changes in cellularity, architecture, and tissue modulus. This gave new insights into host response to cancer as well as leukocyte, cytokine, and matrisome regulation in the tumor microenvironment (TME). Although we had studied a single metastatic site, we identified an extracellular matrix (ECM) gene expression signature, which we named the matrix index, that significantly associated with increased stiffness and disease score. High matrix index distinguished patients with a shorter overall survival in ovarian and twelve other primary cancers, suggesting a common matrix response to human cancer. We used this “deconstruction” analysis of a human TME to build 3D multicellular cultures of human HGSOC cells, primary omental fibroblasts, mesothelial cells, and adipocytes. These cultures reproduce the prognostic matrix index signature, as confirmed by RNAseq and immunofluorescence, of the human cancer biopsies. Using these 3D models, we can study regulation of the matrisome and cancer cell invasion. Similarly, we have conducted multilevel analysis of orthotopic mouse models of HGSOC metastases with relevant oncogenic mutations. This analysis identified significant correlations between the transcriptome, host cell infiltrates, immune response, matrisome, vasculature, and tissue modulus of mouse and human TMEs, with several stromal and malignant cell targets in common. However, each mouse model showed distinct differences and potential vulnerabilities that enabled us to predict response to chemotherapy and an anti-IL-6 antibody. The transcriptional profiles of the mouse tumors that differed in chemotherapy response were able to classify chemotherapy-sensitive and -refractory patient tumors. We believe that these 3D human and mouse models provide useful preclinical tools and may help identify subgroups of HGSOC patients most likely to respond to specific therapies. Citation Format: Frances Balkwill. Modeling the tumor microenvironment of high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA15.
Fibroblast activation protein-targeted-4-1BB ligand agonist amplifies effector functions of intratumoral T cells in human cancer
Authors: Marta Trüb, Franziska Uhlenbrock, Christina Claus, Petra Herzig, Martin Thelen, Vaios Karanikas, Marina Bacac, Maria Amann, Rosemarie Albrecht, Claudia Ferrara-Koller, Daniela Thommen, Sacha Rothschield, Spasenija Savic Prince, Kirsten D Mertz, Gieri Cathomas, Robert Rosenberg, Viola Heinzelmann-Schwarz, Mark Wiese, Didier Lardinois, Pablo Umana, Christian Klein, Heinz Laubli, Abhishek S Kashyap, Alfred Zippelius
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The costimulatory receptor 4-1BB (CD137, TNFRSF9) plays an important role in sustaining effective T cell immune responses and is investigated as target for cancer therapy. Systemic 4-1BB directed therapies elicit toxicity or low efficacy, which significantly hampered advancement of 4-1BB-based immunotherapy. Therefore, targeted delivery of 4-1BB agonist to the tumor side is needed for eliciting antitumor efficacy while avoiding systemic toxicity. Methods We analyzed the immunostimulatory properties of a fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL) by assessing tumor-infiltrating lymphocytes’ (TIL) activity from patients with non-small cell lung cancer and epithelial ovarian cancer. Results Combination treatment with FAP-4-1BBL and T cell receptor stimulation by either anti-CD3 or T cell bispecific antibodies significantly enhanced TIL activation and effector functions, including T cell proliferation, secretion of proinflammatory cytokines and cytotoxicity. Notably, costimulation with FAP-4-1BBL led to de novo secretion of interleukin (IL)−13. This was associated with cytokine-mediated tumor cell apoptosis, which was partially dependent on IL-13 alpha 1/2 receptors and STAT6 phosphorylation. Conclusions Our study provides mechanistic insights into T cell stimulation induced by FAP-4-1BBL in primary human tumors and supports the investigation of FAP-4-1BBL compound in early clinical trials.
Not Black or White but Shades of Gray: Homologous Recombination Deficiency as a Continuous Variable Modulated by RNF168
Authors: Lin Wang, Gerburg M. Wulf
Journal: Cancer Research (2020)

Abstract In this issue of Cancer Research, the study by Krais and colleagues underscores that DNA damage repair by homologous recombination (HR) is not an all-or-nothing phenomenon, but that HR competency comes on a spectrum, ranging from complete deficiency to proficiency. Residual low-level HR in BRCA1-mutant cancer cells turns out to be critically important for their survival and is afforded by low levels of Histone 2A (H2A) ubiquitination resulting from lowered RNF168 levels. The findings raise the possibility that, if ubiquitination of H2A could be enforced by inhibition of deubiquitinases, residual HR in BRCA1mt cells might be extinguished. Extinction of residual HR might improve the therapeutic efficacy of the emerging inhibitors of DNA damage repair. The development of methods to measure HR directly and quantitatively is crucial to develop this field. See related article by Krais et al., p. 2848
Limiting Supplemental Nutrition Assistance Program Eligibility May Increase Sudden Death—Reply
Authors: Alon Peltz, Stephen Rogers, Arvin Garg
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
DIAGNOSIS OF PAEDIATRIC AUTOIMMUNE HEPATITIS BY USING THE COMBINATION OF MULTIPARAMETRIC MRI AND QUANTITATIVE MRCP ANALYSIS
Authors: L Cheng, S Mouchti, K Janowski, G Ridgway, M Goldfinger, A Dennis, M Kelly, C Ferreira, A Borghetto, M Pronicki, M Wozniak, S Chelstowska, E Jurkiewicz, W Grajkowska, S Neubauer, D DeBrota, M Brady, R Banerjee, P Socha
Journal: Hepatology (2019)