tbuckley/cabot-search huggingface dataset:
Monocyte-derived APCs are central to the response of PD1 checkpoint blockade and provide a therapeutic target for combination therapy
Authors: Sjoerd T T Schetters, Ernesto Rodriguez, Laura J W Kruijssen, Matheus H W Crommentuijn, Louis Boon, Jan Van den Bossche, Joke M M Den Haan, Yvette Van Kooyk
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background PD1 immune checkpoint blockade (αPD1 ICB) has shown unparalleled success in treating many types of cancer. However, response to treatment does not always lead to tumor rejection. While αPD1 ICB relies on cytotoxic CD8 + T cells, antigen-presenting cells (APCs) at the tumor site are also needed for costimulation of tumor-infiltrating lymphocytes (TILs). It is still unclear how these APCs develop and function before and during αPD1 ICB or how they are associated with tumor rejection. Methods Here, we used B16 mouse melanoma and MC38 colorectal carcinoma tumor models, which show differential responses to αPD1 ICB. The immune composition of ICB insensitive B16 and sensitive MC38 were extensively investigated using multi-parameter flow cytometry and unsupervised clustering and trajectory analyses. We additionally analyzed existing single cell RNA sequencing data of the myeloid compartment of patients with melanoma undergoing αPD1 ICB. Lastly, we investigated the effect of CD40 agonistic antibody on the tumor-infiltrating monocyte-derived cells during αPD1 ICB. Results We show that monocyte-derived dendritic cells (moDCs) express high levels of costimulatory molecules and are correlated with effector TILs in the tumor microenvironment (TME) after αPD1 ICB only in responding mouse tumor models. Tumor-resident moDCs showed distinct differentiation from monocytes in both mouse and human tumors. We further confirmed significant enrichment of tumor-resident differentiated moDCs in patients with melanoma responding to αPD1 ICB therapy compared with non-responding patients. Moreover, moDCs could be targeted by agonistic anti-CD40 antibody, supporting moDC differentiation, effector T-cell expansion and anti-tumor immunity. Conclusion The combined analysis of myeloid and lymphoid populations in the TME during successful and non-successful PD1 ICB led to the discovery of monocyte-to-DC differentiation linked to expanding T-cell populations. This differentiation was found in patients during ICB, which was significantly higher during successful ICB. The finding of tumor-infiltrating monocytes and differentiating moDCs as druggable target for rational combination therapy opens new avenues of anti-tumor therapy design.
Monomorphic Cutaneous T-Cell Lymphoma in a Patient with Cadaveric Renal Transplant on Immunosuppressive Drugs and Renal Impairment Treated Successfully with Single Agent Brentuximab Vedotin
Authors: Nicholas Cyril D'Cunha, Vinit G Karur, Luke N D'Cunha, Sheree Martinez, Muhammad Saad Khan
Journal: Blood (2017)
Combination sandwich therapy using cyanoacrylate and polyglycolic acid sheets for refractory enterocutaneous fistula closure
Authors: Naoya Tada, Hideki Kobara, Noriko Nishiyama, Ken Ishimura, Kunihisa Uchita, Akira Nishiyama, Tsutomu Masaki
Journal: Endoscopy (2020)

Treating refractory gastrointestinal fistulas is a challenge and often necessitates long hospitalization times. A less invasive endoscopic approach for early complete closure is needed [1] [2]. Possible closure methods include simple filling therapy with cyanoacrylate (Histoacryl; B. Braun, Tokyo, Japan) [3] or polyglycolic acid (PGA) sheets (NEOVEIL; Gunze, Osaka, Japan) [4], or closure with an over-the-scope clip (OTSC; Ovesco Endoscopy AG, Tübingen, Germany) [5], but none have provided satisfactory outcomes. We introduce a novel combination therapy using cyanoacrylate and PGA sheets for fistula closure.
Product Hopping—An Expensive and Wasteful Practice
Authors: Jennifer D. Claytor, Rita F. Redberg
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
BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency
Authors: Manav Gupta, Carla P. Concepcion, Caroline G. Fahey, Hasmik Keshishian, Arjun Bhutkar, Christine F. Brainson, Francisco J. Sanchez-Rivera, Patrizia Pessina, Jonathan Y. Kim, Antoine Simoneau, Margherita Paschini, Mary C. Beytagh, Caroline R. Stanclift, Monica Schenone, D.R. Mani, Chendi Li, Audris Oh, Fei Li, Hai Hu, Angeliki Karatza, Roderick T. Bronson, Alice T. Shaw, Aaron N. Hata, Kwok-Kin Wong, Lee Zou, Steven A. Carr, Tyler Jacks, Carla F. Kim
Journal: Cancer Research (2020)

Inactivation of SMARCA4/BRG1, the core ATPase subunit of mammalian SWI/SNF complexes, occurs at very high frequencies in non-small cell lung cancers (NSCLC). There are no targeted therapies for this subset of lung cancers, nor is it known how mutations in BRG1 contribute to lung cancer progression. Using a combination of gain- and loss-of-function approaches, we demonstrate that deletion of BRG1 in lung cancer leads to activation of replication stress responses. Single-molecule assessment of replication fork dynamics in BRG1-deficient cells revealed increased origin firing mediated by the prelicensing protein, CDC6. Quantitative mass spectrometry and coimmunoprecipitation assays showed that BRG1-containing SWI/SNF complexes interact with RPA complexes. Finally, BRG1-deficient lung cancers were sensitive to pharmacologic inhibition of ATR. These findings provide novel mechanistic insight into BRG1-mutant lung cancers and suggest that their dependency on ATR can be leveraged therapeutically and potentially expanded to BRG1-mutant cancers in other tissues. SIGNIFICANCE: These findings indicate that inhibition of ATR is a promising therapy for the 10% of non-small cell lung cancer patients harboring mutations in SMARCA4/BRG1. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/18/3841/F1.large.jpg.
Ischemic Myocardial Burden Subtended by Computed Tomography–Derived Fractional Flow Reserve (APPROACHFFRCT)
Authors: Abdul Rahman Ihdayhid, Bjarne L. Norgaard, Stephan Achenbach, Nancy Khav, Sara Gaur, Jonathan Leipsic, Nitesh Nerlekar, Kazuhiro Osawa, Toru Miyoshi, Jesper M. Jensen, Takeshi Kimura, Hiroki Shiomi, Andrejs Erglis, Keith G. Oldroyd, Hans Erik Botker, Jagat Narula, Brian S. Ko
Journal: JACC. Cardiovascular imaging (2020)
Allopatric and Sympatric Drivers of Speciation in<i>Alviniconcha</i>Hydrothermal Vent Snails
Authors: Corinna Breusing, Shannon B Johnson, Verena Tunnicliffe, David A Clague, Robert C Vrijenhoek, Roxanne A Beinart
Journal: Molecular Biology and Evolution (2020)

Despite significant advances in our understanding of speciation in the marine environment, the mechanisms underlying evolutionary diversification in deep-sea habitats remain poorly investigated. Here, we used multigene molecular clocks and population genetic inferences to examine processes that led to the emergence of the six extant lineages of Alviniconcha snails, a key taxon inhabiting deep-sea hydrothermal vents in the Indo-Pacific Ocean. We show that both allopatric divergence through historical vicariance and ecological isolation due to niche segregation contributed to speciation in this genus. The split between the two major Alviniconcha clades (separating A. boucheti and A. marisindica from A. kojimai, A. hessleri, and A. strummeri) probably resulted from tectonic processes leading to geographic separation, whereas the splits between co-occurring species might have been influenced by ecological factors, such as the availability of specific chemosynthetic symbionts. Phylogenetic origin of the sixth species, Alviniconcha adamantis, remains uncertain, although its sister position to other extant Alviniconcha lineages indicates a possible ancestral relationship. This study lays a foundation for future genomic studies aimed at deciphering the roles of local adaptation, reproductive biology, and host-symbiont compatibility in speciation of these vent-restricted snails.
The Society of Homoeopaths has no official policy on vaccination
Authors: J. Carlyon
Journal: BMJ (1995)

EDrroR,-Pandora Pound and Shah Ebrahim suggest that patients are asked about their satisfaction in order to achieve greater responsiveness to their needs.One of the outcomes of our survey was that asking about satisfaction produces little useful information.Asking about patients' ex- periences, however, can help to improve standards of care.In our paper the results of the questions concerning satisfaction were shown simply to illustrate that answers to these types of questions are positive despite the obvious problems reported in questions related to patients' actual experiences.
AB0126 Assessment of sulphasalazine (ss) and methotrexate (mt) efficacy in treatment of ankylosing spondylitis (as).(preliminary data)
Authors: SN Tchepeleva, GV Loukina, YA Sigidin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the efficacy of methotrexate and sulphasalazine in patients with active AS. <h3>Methods</h3> 30 patients with AS satisfying the New York criteria for AS were randomly divided into two groups. One group (21 patients) received 1.5–2 g/d SS for 6 months and the other (9 patients) – methotrexate 7.5–10 mg/week. 25 clinical and laboratory criteria were assessed. Positive changes (over 20% from baseline) in 20 and more variables were considered as excellent effect; 14–19, good; 6–13, moderate; 1–5, no response. <h3>Results</h3> 21 patients completed the study (17 on SS and 4 on MT). In SS group there were 2 patients with excellent effect, 6 with good effect, 7 with moderate one and only 2 had no response. 3 patients treated with methotrexate had moderate effect and 1 patient had good one. 5 patients dropped out of the trial due to adverse reactions:3 in MT group (liver enzymes elevations, low back pain, myalgia/ossalgia) and 2 in SS group (allergic rash, taste disorder). We observed several transient side effects. 2 patients from SS group complained of dizziness, that resolved spontaneously. One of them had anaemia, for which he experienced benefit with folic acid. One patient had concentration disorder. <h3>Conclusion</h3> These data suggest that SS is an effective treatment for AS and it is necessary to continue this comparative study.
Effect of N-cadherin knock-down on invasiveness of esophageal squamous cell carcinoma
Authors: L. Ke, H. Wei, L. Na, L. Na, W. Xin, F. Qing-Xia
Journal: Journal of Clinical Oncology (2009)

e15571 Background: Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in esophageal squamous cell carcinoma. Aim: To examine the expressions of N-cadherin and E-cadherin in 62 normal esophageal epithelium specimens, 31 adjacent atypical hyperplasia epithelium specimens and 62 esophageal squamous cell carcinoma specimens, and to investigate the roles of N-cadherin in the invasiveness of esophageal squamous cell carcinoma cell line EC9706 transfected by N-cadherin shRNA.. Methods: PV immunohistochemistry was used to detect the expression pattern of N-cadherin and E-cadherin in 62 normal esophageal epithelium specimens, 31 adjacent atypical hyperplasia epithelium specimens and 62 esophageal squamous cell carcinoma specimens. The invasiveness of esophageal squamous cell carcinoma cell line EC9706 in vitro and in vivo was determined by transwell assay and nude mice experiments after EC9706 was transfected by N-cadherin shRNA. Results: The positive rates of N-cadherin decreased in the sequence of carcinoma, adjacent atypical hyperplasia and normal esophageal tissue, which were 75.8%, 61.3%, 29.0% (P &lt; 0.05), respectively, while those of E-cadherin increased in sequence, which were 40.3%, 71.0% and 95.2% (P &lt; 0.05). The increased expression of N-cadherin and decreased expression of E-cadherin were related to the invasion, differentiation, and lymph node metastasis (P &lt; 0.05). The expression level of N-cadherin decreased in the N- cadherin knocked down cells, and the invasiveness of those cells decreased significantly as well in vitro and in vivo. Conclusions: These results suggest that N-cadherin is an important factor in the invasiveness of esophageal squamous cell carcinoma and N-cadherin may serves as a potential molecular target for biotherapy of esophageal squamous cell carcinoma. No significant financial relationships to disclose.
Covid-19: PM promises inquiry but says it won’t happen during pandemic
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: PM promises inquiry but says it won’t happen during pandemic Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 From the Mother to the Infant
Authors: Andrea Lo Vecchio
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Pediatrics journal
Reply to Francesco Montorsi, Marco Bandini, Alberto Briganti, et al. Re-establishing the Role of Robot-assisted Radical Cystectomy After the 2020 EAU Muscle-invasive and Metastatic Bladder Cancer Guideline Panel Recommendations. Eur Urol 2020;78:489–91
Authors: J. Alfred Witjes, Maria J. Ribal, Antoine G. van der Heijden
Journal: European Urology (2020)
Uterus Modeling From Cell to Organ Level: Towards Better Understanding of Physiological Basis of Uterine Activity
Authors: Yuhang Xu, Haipeng Liu, Dongmei Hao, Michael Taggart, Dingchang Zheng
Journal: IEEE Reviews in Biomedical Engineering (2020)

The relatively limited understanding of the physiology of uterine activation prevents us from achieving optimal clinical outcomes for managing serious pregnancy disorders such as preterm birth or uterine dystocia. There is increasing awareness that multi-scale computational modeling of the uterus is a promising approach for providing a qualitative and quantitative description of uterine physiology. The overarching objective of such approach is to coalesce previously fragmentary information into a predictive and testable model of uterine activity that, in turn, informs the development of new diagnostic and therapeutic approaches to these pressing clinical problems. This article assesses current progress towards this goal. We summarize the electrophysiological basis of uterine activation as presently understood and review recent research approaches to uterine modeling at different scales from single cell to tissue, whole organ and organism with particular focus on transformative data in the last decade. We describe the positives and limitations of these approaches, thereby identifying key gaps in our knowledge on which to focus, in parallel, future computational and biological research efforts.
ATS/ERS/JRS/ALATの公式声明: 特発性肺線維症: 診断および管理に関するエビデンスに基づくガイドライン | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Raghu Ganesh, R Collard Harold, J Egan Jim, J Martinez Fernando, Behr Juergen, K Brown Kevin, V Colby Thomas, Cordier Jean-Francois, R Flaherty Kevin, A Lasky Joseph, A Lynch David, H Ryu Jay, J Swigris Jeffrey, U Wells Athol, Ancochea Julio, Bouros Demosthenes, Carvalho Carlos, Costabel Ulrich, Ebina Masahito, M Hansell David, Johkoh Takeshi, Kim Dong Soon, E King Talmadge, Kondoh Yasuhiro, Myers Jeffrey, L Mueller Nestor, G Nicholson Andrew, Richeldi Luca, Selman Moises, F Dudden Rosalind, S Griss Barbara, L Protzko Shandra, J Schuenemann Holger
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Author Correction: Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease
Authors: Jennifer S. Lees, Claire E. Welsh, Carlos A. Celis-Morales, Daniel Mackay, James Lewsey, Stuart R. Gray, Donald M. Lyall, John G. Cleland, Jason M. R. Gill, Pardeep S. Jhund, Jill Pell, Naveed Sattar, Paul Welsh, Patrick B. Mark
Journal: Nature Medicine (2020)
Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel
Authors: Rawan Faramand, Michael Jain, Verena Staedtke, Hiroshi Kotani, Renyuan Bai, Kayla Reid, Sae Bom Lee, Kristen Spitler, Xuefeng Wang, Biwei Cao, Javier Pinilla, Aleksander Lazaryan, Farhad Khimani, Bijal Shah, Julio C. Chavez, Taiga Nishihori, Asmita Mishra, John Mullinax, Ricardo Gonzalez, Mohammad Hussaini, Marian Dam, Brigett D. Brandjes, Christina A. Bachmeier, Claudio Anasetti, Frederick L. Locke, Marco L. Davila
Journal: Clinical Cancer Research (2020)

One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
Economic considerations on the usage of biologics in the allergy clinic
Authors: Pauline Azzano, Élise Dufresne, Thomas Poder, Philippe Bégin
Journal: Allergy (2020)

Abstract The advent of biologic therapies has transformed care for severe atopic disorders but their high cost poses new challenges with regard to long‐term sustainability and fair allocation of resources. This article covers the basic concepts of cost‐utility analyses and reviews the available literature on cost utility of biologic drugs in atopic disorders. When used within their limits as part of a multi‐dimensional assessment, economic analyses can be extremely useful to guide decision‐making and prioritization of care. Despite the good quality of most cost‐utility analyses conducted for the use of biologics in asthma and other atopic diseases, their conclusions regarding cost‐effectiveness are extremely variable. This is mainly due to the use of inconsistent estimates of health utility benefit with therapy. Development of reliable and validated instruments to measure disutility in atopic disorders and measure of indirect costs in atopic disease are identified as a priority for future research.
Sixty seconds on . . . outbreak
Authors: Abi Rimmer
Journal: BMJ (2020)

The Dustin Hoffman movie?Sadly not, although the film's introduction feels relevant: "The single biggest threat to man's continued dominance on the planet is the virus."Instead, we are concerned with the use of the word "outbreak." Is it bugging people?I should say so.Peter Soulsby, the mayor of Leicester-which has been under local lockdown for the past few weeks-has questioned its use.He is (perhaps justifiably) confused because, despite being told by Public Health England on 15 June that no covid-19 "outbreak" had been identified in his city, the health secretary, Matt Hancock, announced on 18 June that there was an "outbreak" in Leicester. 1 Why does that matter?In this case, because it just adds to the confusion.At the time, Soulsby said that Leicester had only one covid-19 testing station and that the city council did not receive the data it had requested on the number of people who had tested positive until 11 days after Hancock's declaration of an "outbreak." 2 But what does "outbreak" mean?Good question.Public Health England usually defines an outbreak as "two or more people experiencing a similar illness, which appears to be linked to a place." 3 But it can also be "a single case of an unusual or rare infection" or "a greater than expected rate of infection compared with the usual background rate that is expected in that population for that place or time." 4 Confusing . . .Yes-and it gets worse.The World Health Organization describes a disease outbreak as "the occurrence of disease cases in excess of normal expectancy." 5 Should we stop using it?Well, maybe not.Jimmy Whitworth, professor of international public health at the London School of Hygiene and Tropical Medicine, says that it is quite valid to use the term when there are more cases of a disease than expected, as was the case in Leicester. So, "outbreak" isn't cancelled?No, it's still OK.But, as the movie's strapline says, "Try to remain calm.
Horizontal transfer of blaNDM-1-carrying IncX3 plasmid between carbapenem-resistant Enterobacteriaceae in a single patient
Authors: Jin Seok Kim, Young-hee Jin, Sang-Hun Park, Sunghee Han, Hee Soon Kim, Jin Kyung Yu, Jung Im Jang, Junyoung Kim, Chae-Kyu Hong, Jib-Ho Lee, Sang-Me Lee, Young-Hee Oh
Journal: Journal of Infection (2020)