tbuckley/cabot-search huggingface dataset:
MO1-2 Geriatric assessment and clinical outcomes for elderly colorectal cancer patients
Authors: Ayako Doi, Hiroyuki Takeda, Kumiko Umemoto, Hiroyuki Arai, Yoshiki Horie, Takuro Mizukami, Naoki Izawa, Takashi Ogura, Tomoyo Oguri, Yu Sunakawa
Journal: Annals of Oncology (2021)
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease
Authors: Christel Claes, Emma Pascal Danhash, Jonathan Hasselmann, Jean Paul Chadarevian, Sepideh Kiani Shabestari, Whitney E. England, Tau En Lim, Jorge Luis Silva Hidalgo, Robert C. Spitale, Hayk Davtyan, Mathew Blurton-Jones
Journal: Molecular Neurodegeneration (2021)

Abstract Background Disease-associated microglia (DAMs), that surround beta-amyloid plaques, represent a transcriptionally-distinct microglial profile in Alzheimer’s disease (AD). Activation of DAMs is dependent on triggering receptor expressed on myeloid cells 2 (TREM2) in mouse models and the AD TREM2-R47H risk variant reduces microglial activation and plaque association in human carriers. Interestingly, TREM2 has also been identified as a microglial lipid-sensor, and recent data indicates lipid droplet accumulation in aged microglia, that is in turn associated with a dysfunctional proinflammatory phenotype. However, whether lipid droplets (LDs) are present in human microglia in AD and how the R47H mutation affects this remains unknown. Methods To determine the impact of the TREM2 R47H mutation on human microglial function in vivo , we transplanted wild-type and isogenic TREM2-R47H iPSC-derived microglial progenitors into our recently developed chimeric Alzheimer mouse model. At 7 months of age scRNA-seq and histological analyses were performed. Results Here we report that the transcriptome of human wild-type TREM2 and isogenic TREM2-R47H DAM xenografted microglia (xMGs), isolated from chimeric AD mice, closely resembles that of human atherosclerotic foam cells. In addition, much like foam cells, plaque-bound xMGs are highly enriched in lipid droplets. Somewhat surprisingly and in contrast to a recent in vitro study, TREM2-R47H mutant xMGs exhibit an overall reduction in the accumulation of lipid droplets in vivo . Notably, TREM2-R47H xMGs also show overall reduced reactivity to plaques, including diminished plaque-proximity, reduced CD9 expression, and lower secretion of plaque-associated APOE. Conclusions Altogether, these results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.
Combining High-Sensitivity Troponin With the American Heart Association/American College of Cardiology Cholesterol Guidelines to Guide Evolocumab Therapy
Authors: Nicholas A. Marston, Kazuma Oyama, Petr Jarolim, Minao Tang, Peter S. Sever, Anthony C. Keech, Armando Lira Pineda, Huei Wang, Robert P. Giugliano, Marc S. Sabatine, David A. Morrow
Journal: Circulation (2021)
Hospital-Free Days: A Pragmatic and Patient-centered Outcome for Trials among Critically and Seriously Ill Patients
Authors: Catherine L. Auriemma, Stephanie P. Taylor, Michael O. Harhay, Katherine R. Courtright, Scott D. Halpern
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Hospital-Free Days: A Pragmatic and Patient-centered Outcome for Trials among Critically and Seriously Ill Patients." American Journal of Respiratory and Critical Care Medicine, 204(8), pp. 902–909
GATA3 functions downstream of BRCA1 to suppress EMT in breast cancer
Authors: Feng Bai, Li-Han Zhang, Xiong Liu, Chuying Wang, Chenglong Zheng, Jianping Sun, Min Li, Wei-Guo Zhu, Xin-Hai Pei
Journal: Theranostics (2021)

Purpose: Functional loss of BRCA1 is associated with poorly differentiated and metastatic breast cancers that are enriched with cancer stem cells (CSCs). CSCs can be generated from carcinoma cells through an epithelial-mesenchymal transition (EMT) program. We and others have previously demonstrated that BRCA1 suppresses EMT and regulates the expression of multiple EMT-related transcription factors. However, the downstream mediators of BRCA1 function in EMT suppression remain elusive. Methods: Depletion of BRCA1 or GATA3 activates p18INK4C , a cell cycle inhibitor which inhibits mammary epithelial cell proliferation. We have therefore created genetically engineered mice with Brca1 or Gata3 loss in addition to deletion of p18INK4C , to rescue proliferative defects caused by deficiency of Brca1 or Gata3. By using these mutant mice along with human BRCA1 deficient as well as proficient breast cancer tissues and cells, we investigated and compared the role of Brca1 and Gata3 loss in the activation of EMT in breast cancers. Results: We discovered that BRCA1 and GATA3 expressions were positively correlated in human breast cancer. Depletion of BRCA1 stimulated methylation of GATA3 promoter thereby repressing GATA3 transcription. We developed Brca1 and Gata3 deficient mouse system. We found that Gata3 deficiency in mice induced poorly-differentiated mammary tumors with the activation of EMT and promoted tumor initiating and metastatic potential. Gata3 deficient mammary tumors phenocopied Brca1 deficient tumors in the induction of EMT under the same genetic background. Reconstitution of Gata3 in Brca1-deficient tumor cells activated mesenchymal-epithelial transition, suppressing tumor initiation and metastasis. Conclusions: Our finding, for the first time, demonstrates that GATA3 functions downstream of BRCA1 to suppress EMT in controlling mammary tumorigenesis and metastasis.
TGFβ Signaling Activated by Cancer-Associated Fibroblasts Determines the Histological Signature of Lung Adenocarcinoma
Authors: Ryo Sato, Kosuke Imamura, Takashi Semba, Yusuke Tomita, Sho Saeki, Koei Ikeda, Yoshihiro Komohara, Makoto Suzuki, Takuro Sakagami, Hideyuki Saya, Yoshimi Arima
Journal: Cancer Research (2021)

Abstract Invasive lung adenocarcinoma (LADC) can be classified histologically as lepidic, acinar, papillary, micropapillary, or solid. Most LADC tumors manifest several of these histological subtypes, with heterogeneity being related to therapeutic resistance. We report here that in immunodeficient mice, human LADC cells form tumors with distinct histological features, MUC5AC-expressing solid-type or cytokeratin 7 (CK7)-expressing acinar-type tumors, depending on the site of development, and that a solid-to-acinar transition (SAT) could be induced by the tumor microenvironment. The TGFβ-Smad signaling pathway was activated in both tumor and stromal cells of acinar-type tumors. Immortalized cancer-associated fibroblasts (CAF) derived from acinar-type tumors induced SAT in 3D cocultures with LADC cells. Exogenous TGFβ1 or overexpression of an active form of TGFβ1 increased CK7 expression and reduced MUC5AC expression in LADC cells, and knockdown of Tgfb1 mRNA in CAFs attenuated SAT induction. RNA-sequencing analysis suggested that angiogenesis and neutrophil recruitment are associated with SAT in vivo. Our data indicate that CAF-mediated paracrine TGFβ signaling induces remodeling of tumor tissue and determines the histological pattern of LADC, thereby contributing to tumor heterogeneity. Significance: CAFs secrete TGFβ to induce a solid-to-acinar transition in lung cancer cells, demonstrating how the tumor microenvironment influences histological patterns and tumor heterogeneity in lung adenocarcinoma.
P1-2 Safety and efficacy of nivolumab therapy in patients with advanced esophageal squamous cell carcinoma
Authors: Seitaro Shimada, Takahiro Tsushima, Hiromichi Shirasu, Takeshi Kawakami, Satoshi Hamauchi, Akiko Todaka, Tomoya Yokota, Kentaro Yamazaki, Akira Fukutomi, Yusuke Onozawa, Hirofumi Yasui
Journal: Annals of Oncology (2021)
Limitations to Contingency Measures: Reflections from COVID-19 Surges in the UK
Authors: Caitlin Gordon, Sarah Yardley, David A. Lomas, Sarah J. L. Edwards
Journal: The American Journal of Bioethics (2021)

Click to increase image sizeClick to decrease image sizeThis article refers to:Between Usual and Crisis Phases of a Public Health Emergency: The Mediating Role of Contingency MeasuresThis article is referred to by:Ethics Frameworks and Beyond—Advancing Our Understanding of the Contingency Phase to Improve Health Care Quality During Public Health Emergencies ACKNOWLEDGEMENTSWe wish to acknowledge discussions of these issues which were raised at the UCLH Clinical Ethics Advisory Committee (CEAC) and the North Central London COVID-19 Ethics Advisory Group during the peak of the second surge in January 2021.
P37-7 Investigation of discarded anticancer agents after preparation in Nagoya Memorial Hospital
Authors: Satoshi Hibi, Megumi Kabeya, Nobuto Ito, Shu Yuasa, Yuko Shirokawa, Kengo Nanya, Yuko Kato, Naohiro Matsunaga, Yoshiaki Marumo, Takashi Yoshida, Ryuichi Furuta, Takae Kataoka, Satoshi Kayukawa, Kenji Ina
Journal: Annals of Oncology (2021)
Virchow at 200 and Lown at 100 — Physicians as Activists
Authors: Salvatore Mangione, Mark L. Tykocinski
Journal: New England Journal of Medicine (2021)

The Covid-19 pandemic has forced many people to reconsider what medicine is all about. But debate over what doctoring is — and what it is not — is nothing new, and 2021 marks significant anniversaries of the births of two physicians who took a broad view of medicine.
MO31-3 Intratumor microbiome analysis of pancreatic cancer by analyzing the fresh frozen tissues obtained by EUS-FNA
Authors: Shintaro Nakano, Yasuyuki Kawamoto, Kazuaki Harada, Ken Ito, Rika Saito, Takahiro Yamamura, Satoshi Yuki, Hajime Hirata, Ryutaro Furukawa, Yunosuke Takishin, Kousuke Nagai, Masaki Kuwatani, Yoshito Komatsu, Naoya Sakamoto
Journal: Annals of Oncology (2021)
経カテーテル三尖弁弁輪形成術SCOUT試験30日結果の初期実現可能性研究【Powered by NICT】
Authors: T Hahn Rebecca, U Meduri Christopher, J Davidson Charles, Lim Scott, M Nazif Tamim, J Ricciardi Mark, Rajagopal Vivek, Ailawadi Gorav, A Vannan Mani, D Thomas James, Fowler Dale, Rich Stuart, Martin Randy, Ong Geraldine, Groothuis Adam, Kodali Susheel
Journal: Journal of the American College of Cardiology (2017)
A sunshine payment act for the UK
Authors: Sonia Macleod
Journal: BMJ (2021)

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 A sunshine payment act for the UK Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Linking Biophysical and Transcriptional Profiles of In Vivo-Treated Human Leukemias on a Single-Cell Level Uniquely Resolves Subpopulations of Response
Authors: Mark A. Murakami, Mark M Stevens, Robert J Kimmerling, Alejandro J Gupta, Huiyun Liu, Sanjay M. Prakadan, Alex K. Shalek, Scott R. Manalis, David M. Weinstock
Journal: Blood (2017)
Seizure Prophylaxis After Spontaneous Intracerebral Hemorrhage
Authors: Felipe J. S. Jones, Paula R. Sanches, Jason R. Smith, Sahar F. Zafar, Deborah Blacker, John Hsu, Lee H. Schwamm, Joseph P. Newhouse, Michael B. Westover, Lidia M. V. R. Moura
Journal: JAMA Neurology (2021)

Limited evidence is available concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH).
P1-5 Retrospective analysis of the efficacy and safety of nivolumab in patients with treatment-refractory esophageal cancer
Authors: Toshiaki Kobayashi, Hiroyasu Oda, Koushi Sukeno, Akira Tsunoda, Yasutaka Tono, Mikiya Ishihara, Kanako Saito, Yoshiki Yamashita, Toshiro Mizuno
Journal: Annals of Oncology (2021)
International Consensus for the Dosing of Corticosteroids in <scp>Childhood‐Onset</scp> Systemic Lupus Erythematosus With Proliferative Lupus Nephritis
Authors: Nathalie E. Chalhoub, Scott E. Wenderfer, Deborah M. Levy, Kelly Rouster‐Stevens, Amita Aggarwal, Sonia I. Savani, Natasha M. Ruth, Thaschawee Arkachaisri, Tingting Qiu, Angela Merritt, Karen Onel, Beatrice Goilav, Raju P. Khubchandani, Jianghong Deng, Adriana R. Fonseca, Stacy P. Ardoin, Coziana Ciurtin, Ozgur Kasapcopur, Marija Jelusic, Adam M. Huber, Seza Ozen, Marisa S. Klein‐Gitelman, Simone Appenzeller, André Cavalcanti, Lampros Fotis, Sern Chin Lim, Rodrigo M. Silva, Julia Ramírez‐ Miramontes, Natalie L. Rosenwasser, Claudia Saad‐Magalhaes, Dieneke Schonenberg‐Meinema, Christiaan Scott, Clovis A. Silva, Sandra Enciso, Maria T. Terreri, Alfonso‐Ragnar Torres‐Jimenez, Maria Trachana, Sulaiman M. Al‐Mayouf, Prasad Devarajan, Bin Huang, Hermine I. Brunner
Journal: Arthritis & Rheumatology (2021)

Objective To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood‐onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. Methods Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood‐onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood‐onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR‐recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. Results Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3–5). Validation of the SSR for up to 6 months post–kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). Conclusion The SSR represents an international consensus on CS dosing for use in patients with childhood‐onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
The genetic architecture of depression in samples with East Asian ancestry
Authors: R Walters, I Millwood, K Lin, Y Chen, Z Chen
Journal: JAMA Psychiatry (2021)

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European (EUR) descent. This limits our understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.
Objectives: to investigate the genetics of depression across East Asian and European cultural contexts and outcome definitions.
Design: Genome-wide association studies, followed by meta-analysis. 
Setting: Nine cohort and case-control studies from China, Taiwan, USA and UK. 
Participants: 15,771 depression cases and 178,777 controls of East Asian descent (EAS). 
Exposures: Associations of genetic variants with depression risk were assessed using generalised linear mixed models and logistic regression. The results were combined across studies using fixed effects meta-analyses. These were subsequently also meta-analysed with the largest published GWAS for depression in EUR samples. Additional meta-analyses were carried out separately by outcome definition (clinical vs symptom-based) and region (East Asian countries vs Western countries). 
Main outcomes and measures: Depression status was defined based on health records and self-report questionnaires.
Results: In total we identified five novel associations, including one in the EAS meta-analysis for broad depression: rs4656484 (beta=-0.018, SE=0.003, P=4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (P=5.03x10-9). Both associations were specific to EAS samples (P=0.53 and P=0.28 in EUR, respectively). Only 11% of depression loci previously identified in EUR reached nominal significance levels in the EAS samples. The trans-ancestry genetic correlation estimates with depression in EUR ranged from 0.223 to 0.558, depending on the outcome definition. Clinical depression risk was negatively genetically correlated with BMI in EAS (rg=-0.212), contrary to findings from EUR samples.
Conclusions and relevance: Our results suggest that cultural differences further add to the heterogeneity of depression and thereby impact on the genetic architecture. This cautions against generalising findings about depression risk factors across populations and highlights the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
Authors: Jamie Lopez Bernal, Nick Andrews, Charlotte Gower, Eileen Gallagher, Ruth Simmons, Simon Thelwall, Julia Stowe, Elise Tessier, Natalie Groves, Gavin Dabrera, Richard Myers, Colin N J Campbell, Gayatri Amirthalingam, Matt Edmunds, Maria Zambon, Kevin E Brown, Susan Hopkins, Meera Chand, Mary Ramsay
Journal: New England Journal of Medicine (2021)

BackgroundThe B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear.MethodsWe used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status.Download a PDF of the Research Summary.ResultsEffectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant.ConclusionsOnly modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.) Quick Take Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant 1m 29s
The mismeasure of conservation
Authors: Robert L. Pressey, Piero Visconti, Madeleine C. McKinnon, Georgina G. Gurney, Megan D. Barnes, Louise Glew, Martine Maron
Journal: Trends in Ecology & Evolution (2021)

One of the basic purposes of protected areas and other effective area-based conservation interventions is to achieve conservation impact, the sum of avoided biodiversity loss and promoted recovery relative to outcomes without protection. In the context of the Convention on Biological Diversity's negotiations on the post-2020 Global Biodiversity Framework, we find that targets for area-based interventions are framed overwhelmingly with measures that fail to inform decision-makers about impact and that risk diverting limited resources away from achieving it. We show that predicting impact in space and time is feasible and can provide the basis for global guidance for jurisdictions to develop targets for conservation impact and shift investment priorities to areas where impact can be most effectively achieved.
Atrial Fibrillation
Authors: Jayson R. Baman, Rod S. Passman
Journal: JAMA (2021)

Paul L. Hess, MD, MHS; Jeff S. Healey, MD, MSc; Christopher B. Granger, MD; Stuart J. Connolly, MD, MS; Paul D. Ziegler, MS; John H. Alexander, MD, MHS; Peter R. Kowey, MD; Christian T. Ruff, MD, MPH; Greg Flaker, MD; Jonathan L. Halperin, MD; Robert G. Hart, MD; Renato D. Lopes, MD, PhD, MHS
Busulfan Pharmacogenetics and Drug Exposure in Cancer Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Jai N Patel, Issam Hamadeh, Qing Zhang, Taylor Brown, Nury M Steuerwald, Alicia Hamilton, Lawrence J Druhan, Jiaxian He, James T Symanowski, Mohammed J Hussain, Jigar Trivedi, Michael Richard Grunwald, Nilanjan Ghosh, Belinda Rene Avalos, Edward A Copelan
Journal: Blood (2017)
MO5-4 Angiogenesis-related factors associated with nivolumab efficacy after ramucirumab therapy in advanced gastric cancer
Authors: Yuki Matsubara, Hideaki Bando, Takatsugu Ogata, Taiko Nakazawa, Kyoko Kato, Kazuki Nozawa, Yukiya Narita, Kazunori Honda, Toshiki Masuishi, Shigenori Kadowaki, Masashi Ando, Masahiro Tajika, Kei Muro, Hiromichi Ebi
Journal: Annals of Oncology (2021)
Cancer-cell-biomimetic Upconversion nanoparticles combining chemo-photodynamic therapy and CD73 blockade for metastatic triple-negative breast cancer
Authors: Feiyang Jin, Jing Qi, Di Liu, Yuchan You, Gaofeng Shu, Yan Du, Jun Wang, Xiaoling Xu, Xiaoying Ying, Jiansong Ji, Yongzhong Du
Journal: Journal of Controlled Release (2021)