tbuckley/cabot-search huggingface dataset:
Abstract PR03: Metabolic control of Polycomb Repressive Complex 2 in Lung Disease and Lung Cancer
Authors: Mojtaba Bakhtiari, Aria L. Byrd, Fan Chen, Alexsandr Lukyanchuk, Tanner J. DuCote, Christine Fillmore Brainson
Journal: Cancer Research (2020)

Abstract Dysregulated epigenetic control of lung lineage fate is believed to be a major driver of lung disease, including plasticity in lung cancer. Our laboratory has observed a marked decrease in Polycomb Repressive Complex 2 (PRC2) activity in bronchiolar epithelium of COPD patients, poorly differentiated adenocarcinomas and the majority of squamous cell carcinomas. Interestingly, the PRC2 methyltransferase EZH2 is still highly expressed in many of these tissues, suggesting a de-coupling of EZH2 and PRC2 activity. A mouse model of lineage switching from adenocarcinoma to squamous lung cancer clearly showed that loss of PRC2 activity was a catalyst to epigenetic reprogramming. This model also showed increased infiltration of neutrophils, which are known to produce large amounts of superoxide. Our current hypothesis is that oxidative stress, in part through neutrophil recruitment to lung tissue, drives the loss of PRC2 activity through metabolic changes. To support this hypothesis, we have shown that a redox-sensitive enzyme in the methionine pathway, cystathionine beta synthase (CBS), is expressed in COPD and lung cancer and modulates PRC2 activity. Enforced CBS expression drives global decrease in the PRC2-mediated histone marked, H3K27me3, and increased expression of genes expressed by basal cells of the lung, including KRT5, SOX2 and PD-L1. Furthermore, we have found that PRC2 activity can be stabilized through restriction of methionine levels or knock-down of CBS, leading to increased sensitivity of cells to chemotherapy and radiation treatments. PRC2-low epigenetic states can also be exploited – either pharmacological or genetic perturbation of EZH2 led to sensitivity to several classes of drugs, including immunotherapies. Our future studies include using Stable Isotope Resolved Metabolomics (SIRM) to understand how oxidative stress alters the methionine cycle and ultimately changes the stability and function of the PRC2 complex, and to use this information to design better therapeutic strategies. Work supported by AACR Innovation and Discovery Grant, American Cancer Society 133123-RSG-19-081-01-TBG and IRG-85-001-25, NCI R01 CA237643, NIGMS P20 GM121327-03, NIEHS T32 5T32ES007266-30, NCI T32 CA165990 and NHLBI F31 HL151111-01. Citation Format: Mojtaba Bakhtiari, Aria L. Byrd, Fan Chen, Alexsandr Lukyanchuk, Tanner J. DuCote, Christine Fillmore Brainson. Metabolic control of Polycomb Repressive Complex 2 in Lung Disease and Lung Cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PR03.
Essential Medicines Identified for Future Public Health Emergencies
Authors: Rebecca Voelker
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
159P Open surgery can improve the 3-year postoperative survival in some patients with advanced gastric cancer compared with laparoscopic surgery: A multicenter, propensity score matching, in-depth analysis
Authors: Z-N. Huang, W-W. Qiu, T-X. Lin, Q-Y. Chen, C-H. Zheng, P. Li, J-W. Xie, J-B. Wang, J-X. Lin, J. Lu, L-L. Cao, M. Lin, R-H. Tu, J-L. Lin, H-L. Zheng, C. Huang
Journal: Annals of Oncology (2020)
Delivering better value colonoscopy: bridging the gap with FIT
Authors: Robert P H Logan, Willie Hamilton
Journal: Gut (2020)

Colorectal cancer (CRC) survival is slowly improving in the Western world. To a considerable extent, this reflects earlier detection, either by a screening programme, or by earlier diagnosis in patients with symptoms. However, symptoms on their own are poor predictors of CRC, so this improvement comes at a cost – a considerable increase in the demand for colonoscopy – putting many endoscopy facilities under strain. So how can we deliver even better outcomes for patients at risk of CRC during, and after the COVID-19 pandemic?

The important paper from D’Souza et al in Gut adds to a growing body of research examining if Faecal Immunochemical Test (FIT)can be used to target colonoscopy to those patients most likely to harbour CRC and possibly obviate the need for colonoscopy in others.1 D’Souza et al report on the use of the HM-JACKarc assay, one of the most used assays in the UK. For this assay, the limit of quantitation (the lowest value for reliable clinical use) is 7 µg Hb/g, though the assay can detect values as low as 2 µg Hb/g, although with decreasing reliability.2 One strength of D’Souza et al’ s paper is its large size, allowing examination of three possible definitions of a ‘positive’ test, as well as other demographic features, such as age, gender, deprivation and ethnicity. Unlike in previous studies, these four features transpired to have little predictive value, as other studies have also reported, though with small numbers in some of the …
Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT
Authors: Victor Fernandes Vieira, Estelle Dubruc, Wassim Raffoul, John O. Prior, Marie Meyer
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of a 45-year-old woman with a history of right breast reconstruction with silicone implant for breast cancer. An 18 F-FDG PET/CT performed several years later revealed the presence of 18 F-FDG–avid nodules at the periphery of the silicone implant, in the right internal mammary chain, and in the contralateral breast. Needle core biopsies were positive for bilateral silicone granulomas, without any sign of malignancy. This case displays intense 18 F-FDG uptake in silicone granulomas affecting the contralateral breast after implant reconstruction.
England set to open specialist surgical mesh removal centres in April
Authors: Clare Dyer
Journal: BMJ (2020)

A network of specialist surgical mesh removal centres is to be set up around England, with a launch planned for April 2021.

The move implements a recommendation of the review,1 chaired by the Conservative peer and former health minister Julia Cumberlege, into three treatments which caused avoidable harm. These included the use of transvaginal tape and pelvic mesh to treat pelvic organ prolapse and urinary incontinence.

The review, which published its report in July, heard “harrowing” stories about women left with serious complications. The mesh is hard to remove and only a few surgeons in the UK are able to carry out the procedure.

The use of surgical mesh for urinary incontinence …
Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity*
Authors: R. Laskar, A. Ferreiro‐Iglesias, D.T. Bishop, M.M. Iles, P.A. Kanetsky, B.K. Armstrong, M.H. Law, A.M. Goldstein, J.F. Aitken, G.G. Giles, H.A. Robbins, A.E. Cust
Journal: British Journal of Dermatology (2020)

Background Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. Objectives We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. Methods We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case–control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. Results When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. Conclusions We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.
Using joint modelling to assess the association between a time-varying biomarker and a survival outcome: an illustrative example in respiratory medicine
Authors: Yuntao Chen, Douwe Postmus, Martin R. Cowie, Holger Woehrle, Karl Wegscheider, Anita K. Simonds, Marike Boezen, Virend K. Somers, Helmut Teschler, Christine Eulenburg
Journal: European Respiratory Journal (2020)

<b>Joint modelling is a valuable method to accurately estimate the association between a time-varying biomarker and a survival outcome. The idea of the joint modelling closely reflects contemporary trends in medicine: personalised and dynamic.</b>https://bit.ly/3pbMBFX
How IT preparedness helped to create a digital field hospital to care for COVID-19 patients in S. Korea
Authors: Se Young Jung, Ho-Young Lee, Hee Hwang, Keehyuck Lee, Rong-min Baek
Journal: npj Digital Medicine (2020)

South Korea has overseen one of the worst COVID-19 outbreaks outside China with over 8162 confirmed cases reported by 15 March 2020.The government succeeded in curbing the spread of the disease until mid-February.However, the number of confirmed cases exponentially increased since mid-February, when the number of cases increased because of a secretive religious organization in Daegu, changing the strategy from containment to mitigation of COVID-19, as the government failed to prevent mass infection via intensive quarantine and extensive epidemiological intervention (Fig. 1).In Daegu, the medical system was at the brink of collapse.Although the number of new patients with COVID-19 increased rapidly, patients waiting to be admitted suddenly deteriorated and died at home.In order to prevent the collapse of the entire medical system, the government started to operate "community treatment centers (CTCs)."In addition, the government applied the standards for hospitalization in the national negative pressure care units more strictly.CTCs are facilities that are under the care of the daily medical staff.Before the admittance of patients with COVID-19, the principle was that all individuals infected with COVID-19 would be hospitalized and treated in a negative pressure room, regardless of their risk.However, after experiencing mass dissemination of COVID-19 in Daegu, the Korean government revised the triage strategy to prevent the depletion of medical resources.
Thymus involution sets the clock of the aging T-cell landscape: Implications for declined immunity and tissue repair
Authors: Yehezqel Elyahu, Alon Monsonego
Journal: Ageing Research Reviews (2020)

Aging is generally characterized as a gradual increase in tissue damage, which is associated with senescence and chronic systemic inflammation and is evident in a variety of age-related diseases. The extent to which such tissue damage is a result of a gradual decline in immune regulation, which consequently compromises the capacity of the body to repair damages, has not been fully explored. Whereas CD4 T lymphocytes play a critical role in the orchestration of immunity, thymus involution initiates gradual changes in the CD4 T-cell landscape, which may significantly compromise tissue repair. In this review, we describe the lifespan accumulation of specific dysregulated CD4 T-cell subsets and their coevolution with systemic inflammation in the process of declined immunity and tissue repair capacity with age. Then, we discuss the process of thymus involution—which appears to be most pronounced around puberty—as a possible driver of the aging T-cell landscape. Finally, we identify individualized T cell-based early diagnostic biomarkers and therapeutic strategies for age-related diseases.
Lipid Profiles and Heart Failure Risk
Authors: Clemens Wittenbecher, Fabian Eichelmann, Estefanía Toledo, Marta Guasch-Ferré, Miguel Ruiz-Canela, Jun Li, Fernando Arós, Chih-Hao Lee, Liming Liang, Jordi Salas-Salvadó, Clary B. Clish, Matthias B. Schulze, Miguel Ángel Martínez-González, Frank B. Hu
Journal: Circulation Research (2020)

Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF.We aimed to link single lipid metabolites and lipidomics networks to the risk of developing HF.Discovery analyses were based on 216 targeted lipids in a case-control study (331 incident HF cases and 507 controls, matched by age, sex, and study center), nested within the PREDIMED (Prevención con Dieta Mediterránea) study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multistep workflow, including machine learning-based identification of the HF-related network clusters, and regression-based discovery of the HF-related lipid patterns within these clusters. If available, significant findings were externally validated in a subsample of the EPIC-Potsdam cohort (2414 at-risk participants, including 87 incident HF cases). After confounder-adjustments, 2 lipids were significantly associated with HF risk in both cohorts: CER (ceramide) 16:0 (relative risk [RR] per SD in PREDIMED, 1.28 [95% CI, 1.13-1.47]) and phosphatidylcholine 32_0 (RR per SD in PREDIMED, 1.23 [95% CI, 1.08-1.41]). Additionally, lipid patterns in several network clusters were associated with HF risk in PREDIMED. Adjusted for standard risk factors, an internally cross-validated score based on the significant HF-related lipids that were identified in the network analysis in PREDIMED was associated with a higher HF risk (20 lipids, RR per SD, 2.33 [95% CI, 1.93%-2.81%). Moreover, a lipid score restricted to the externally available lipids was significantly associated with HF incidence in both cohorts (6 lipids, RRs per SD, 1.30 [95% CI, 1.14-1.47] in PREDIMED, and 1.46 [95% CI, 1.17-1.82] in EPIC-Potsdam).Our study identified and validated 2 lipid metabolites and several lipidomics patterns as potential novel biomarkers of HF risk. Lipid profiling may capture preclinical molecular alterations that predispose for incident HF. Registration: URL: https://www.isrctn.com/ISRCTN35739639; Unique identifier: ISRCTN35739639.
Recent Progress in the Synergistic Combination of Nanoparticle‐Mediated Hyperthermia and Immunotherapy for Treatment of Cancer
Authors: Zachary R. Stephen, Miqin Zhang
Journal: Advanced Healthcare Materials (2020)

Abstract Immunotherapy has demonstrated great clinical success in certain cancers, driven primarily by immune checkpoint blockade and adoptive cell therapies. Immunotherapy can elicit strong, durable responses in some patients, but others do not respond, and to date immunotherapy has demonstrated success in only a limited number of cancers. To address this limitation, combinatorial approaches with chemo‐ and radiotherapy have been applied in the clinic. Extensive preclinical evidence suggests that hyperthermia therapy (HT) has considerable potential to augment immunotherapy with minimal toxicity. This progress report will provide a brief overview of immunotherapy and HT approaches and highlight recent progress in the application of nanoparticle (NP)‐based HT in combination with immunotherapy. NPs allow for tumor‐specific targeting of deep tissue tumors while potentially providing more even heating. NP‐based HT increases tumor immunogenicity and tumor permeability, which improves immune cell infiltration and creates an environment more responsive to immunotherapy, particularly in solid tumors.
The genetic landscape of choroid plexus tumors in children and adults
Authors: Christian Thomas, Patrick Soschinski, Melissa Zwaig, Spyridon Oikonomopoulos, Konstantin Okonechnikov, Kristian W Pajtler, Martin Sill, Leonille Schweizer, Arend Koch, Julia Neumann, Ulrich Schüller, Felix Sahm, Laurèl Rauschenbach, Kathy Keyvani, Martin Proescholdt, Markus J Riemenschneider, Jochen Segewiß, Christian Ruckert, Oliver Grauer, Camelia-Maria Monoranu, Katrin Lamszus, Annarita Patrizi, Uwe Kordes, Reiner Siebert, Marcel Kool, Jiannis Ragoussis, William D Foulkes, Werner Paulus, Barbara Rivera, Martin Hasselblatt
Journal: Neuro-Oncology (2020)

Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there are reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially in choroid plexus carcinomas (CPCs).DNA methylation profiling and RNA-sequencing was performed in a series of 47 CPTs. Samples comprised 35 choroid plexus papillomas (CPPs), 6 atypical choroid plexus papillomas (aCPPs) and 6 CPCs plus three recurrences thereof. Targeted TP53 and TERT promotor sequencing was performed in all samples. Whole exome sequencing (WES) and linked-read whole genome sequencing (WGS) was performed in 25 and 4 samples, respectively.Tumors comprised the molecular subgroups "pediatric A" (N=11), "pediatric B" (N=12) and "adult" (N=27). Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments (gains of Chr1, 2 and 21q in "pediatric B" and gains of Chr5 and 9 and loss of Chr21q in "adult"). RNA sequencing yielded a novel CCDC47-PRKCA fusion transcript in one adult choroid plexus papilloma patient with aggressive clinical course; an underlying Chr17 inversion was demonstrated by linked-read WGS. WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children. On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015).Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course.
Metaiodobenzylguanidine Imaging Comes of Age: A New Arrow in the Prognostic Quiver for Heart Failure Patients⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: H. William Strauss, Michelle N. Johnson, Heiko Schöder, Nagara Tamaki
Journal: Journal of the American College of Cardiology (2010)
190P Outcomes from the Asian region of the phase III APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for patients (pts) with resected pancreatic cancer (PC)
Authors: J. Oh Park, C-P. Li, H-M. Chang, Y.S. Shan, J. Bendell, B. Garlipp, H. Hatoum, B. Laquente Saez, T. Salminen, H. Oettle, J. Kocsis, R. Lopez, S. Dowden, M. Karthaus, B. Lu, D. McGovern, S. Banerjee, M. Tempero, D-Y. Oh
Journal: Annals of Oncology (2020)
T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease
Authors: JW Gratama, A Naipal, P Oljans, FE Zwaan, LF Verdonck, T de Witte, JM Vossen, RL Bolhuis, GC de Gast, J Jansen
Journal: Blood (1984)
Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis
Authors: Gianluigi Savarese, Lina Benson, Johan Sundström, Lars H. Lund
Journal: European Journal of Heart Failure (2020)

Abstract Aims Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population. Methods and results Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use. Conclusions In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19.
T Cells in Coronary Artery Disease: Different Effects of Different T-Cell Subsets⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Pål Aukrust, Arne Yndestad, Wiggo J. Sandberg, Lars Gullestad, Jan K. Damås
Journal: Journal of the American College of Cardiology (2007)
Phase II Study of the Bortezomib-Melphalan-Prednisolone Induction Therapy Followed By Lenalidomide-Plus-Dexamethasone Consolidation and Lenalidomide Maintenance in Non-Transplant Eligible Patients with Newly Diagnosed Symptomatic Multiple Myeloma (CANDLE trial)
Authors: Tadao Ishida, Shuji Ozaki, Hideo Kimura, Koumei Kubo, Kazutaka Sunami, Naoki Takezako, Hiroyuki Fujita, Toshiaki Hayashi, Toru Kiguchi, Takeshi Kobayashi, Satoshi Yamamoto, Hiroyuki Takamatsu, Hiroshi Kosugi, Kensuke Ohta, Rika Sakai, Hiroshi Handa, Takashi Hisatomi, Yu Abe, Ko Sasaki, Eijiro Omoto, Hirokazu Murakami, Kazuyuki Shimizu
Journal: Blood (2017)