tbuckley/cabot-search huggingface dataset:
Health, employment, and economic change, 1973-2009: repeated cross sectional study
Authors: Mel Bartley
Journal: BMJ (2012)

The paper

Health, employment, and economic change, 1973-2009: repeated cross sectional study by Jonathan William Minton and colleagues ( BMJ 2012;344:e2316, doi:10.1136/bmj.e2316)

Abstract

Objective —To see whether adverse relations between social class, health, and economic activity, observed between 1973 and 1993 and previously identified in a 1996 BMJ paper, were still apparent between 1994 and 2009 despite improvements in the general economic climate and overall population health.

Design —Replication of repeated cross sectional analysis from the original paper, using the same source (the General Household Survey) and occupation coding scheme, but extended from the period 1973-93 to 1973-2009, and including women as well as men.

Participants —Men and women aged 20-59 years in each annual survey between 1973 and 2009.

Main outcome measures —Change over time in class specific rates of employment, unemployment, and economic inactivity within subgroups of respondents.

Results —Overall employment rates have decreased for men of working age while increasing for working age women. For men in particular, the gradient of these changes seems to depend on occupational group. Over 37 years, the difference in occupational group specific economic inactivity and employment rates between people reporting and those not reporting a limiting long term illness has increased substantially.

Conclusion —Between 1973 and 2009, the relation between good health and securing and sustaining employment has strengthened for men and women. For men, this has been caused by employment rates decreasing and economic inactivity rates increasing among men with poor health. For women, this has largely been because of a general trend of increased employment and reduced economic inactivity occurring among healthier women, but not in women of poorer health. Some evidence suggests that, since 2005, the relation between health, employment, and economic inactivity for women in the top two occupational groups has become more like that for …
Study Puts Eggs and Dietary Cholesterol Back on the Radar
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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Abstract P5-07-07: The immune microenvironment of ductal carcinoma <i>in situ</i> of the breast
Authors: N Yamashita, Y Hisamatsu, T Shigechi, E Tokunaga, H Saeki, E Oki, Y Maehara
Journal: Cancer Research (2019)

Abstract Background: The importance of tumor-infiltrating lymphocytes (TIL) in invasive breast carcinoma for tumor development and therapeutic response is widely accepted. However, the immune microenvironment of breast ductal carcinoma in situ (DCIS) has not been fully elucidated. Evasion of immune surveillance is a necessary step in tumor evolution. In DCIS, the tumor cells are relatively protected from the immune system due to an myoepithelial cell layer and basement membrane, and intraductal immune cells are rarely detected. In contrast, in invasive disease, cancer cells and immune cells are often intermingled. Thus, understanding the immune microenviroment of in situ to invasive carcinoma transition might be particularly important to identify novel targets for early stage of tumor invasion. Aims: The aim of this study is to evaluate the clinical importance of TILs in DCIS. Methods: TILs were assessed in 133 DCIS samples with or without microinvasive disease according to the proposed method from the International Immuno-Oncology Working Group on Breast Cancer. In addition, the relationship between TILs in DCIS and clinicopathological features was evaluated. Results: TILs are present in most DCIS in varying levels. The median proportion of TILs in DCIS was 14%. Only a minority of DCIS showed &amp;gt;50% TILs, which represented only 12.8% of all cases. High TILs in DCIS was significantly associated with comedo necrosis (p&amp;lt;0.0001), high nuclear grade (p=0.0030), ER negativity (p&amp;lt;0.0001), PR negativity (p&amp;lt;0.0001), HER2 positivity (p=0.0030). Triple negative DCIS and HER2 positive DCIS had significantly higher level of TILs (p=0.0008). No correlation was demonstrated between TILs and recurrence risk. Conclusions: High TILs in DCIS was significantly associated with adverse histopathologic features. Further characterization of immune environment of DCIS may be essential for immunotherapy and breast cancer prevention. Citation Format: Yamashita N, Hisamatsu Y, Shigechi T, Tokunaga E, Saeki H, Oki E, Maehara Y. The immune microenvironment of ductal carcinoma in situ of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-07.
Abstract P3-03-28: Withdrawn
Authors: T-K Yoo, BJ Chae, JY Ahn, J Ryu, YH Eom, WC Park, BJ Song
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Yoo T-K, Chae BJ, Ahn JY, Ryu J, Eom YH, Park WC, Song BJ. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-28.
Defending patients from judgments
Authors: Ashley Albert
Journal: BMJ (2014)

The patient had no identification on him—all we knew was that he had walked out in front of a car. Then we found drug paraphernalia in his clothing, and from that point on it seemed as if this had become his identification. As his healthcare team, it seemed as if we had gone from knowing nothing to assuming almost everything about him. The drugs told his story for him, and as he was unconscious, he was unaware of the opinions and assessments …
Abstract P5-07-11: Transcriptome alteration of breast cancer cells in the process of tumor-associated macrophages-promoted metastasis
Authors: M Long, M Yang, J An, H Su, R Liu
Journal: Cancer Research (2019)

Abstract Introduction: Tumor-associated macrophages (TAMs) play an important role in the process of tumor metastasis. Previous studies have shown that TAMs induce breast cancer cells undergo epithelial-mesenchymal transition (EMT) by secreting CCL18. Reciprocally, the induced mesenchymal-like breast cancer cells activate macrophages into a TAM-like phenotype via secreting the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), forming a positive feedback loop that is essential to breast cancer metastasis. Methods: To better understand the underlying mechanism that links this positive feedback loop to breast cancer metastasis, a TAMs-induced EMT cell model (MCF-7) was used. RNA-seq was used to compare the transcriptome of MCF-7 cells which were cocultured with TAMs and those with or without monocyte-derived macrophages (MDMs). Results were further verified by qRT-PCR. Results: Among 811 known protein-coding genes with reliable readouts, 42 were significantly changed between groups (P&amp;lt;0.001). Further analysis using KEGG, Reactome and Wikipathways databases found that these 42 genes were enriched in 15 signal pathways (P&amp;lt;0.01). According to their biological function, these pathways can be divided into 5 functional groups: SUMOylation related, virus related, immune related, interferon related and cytokine related. The last 3 groups demonstrated that our model were representative and able to provide some real and useful information, while SUMOylation and virus related signal pathways have never been reported to be involved in TAMs induced breast cancer metastasis. Conclusion: We investigated the transcriptome alteration of MCF-7 cells in the process of TAMs-promoted metastasis. Results from bioinformatic analysis indicated SUMOylation and virus related signal pathways in the process of TAMs induced breast cancer metastasis, which are yet to be confirmed. Citation Format: Long M, Yang M, An J, Su H, Liu R. Transcriptome alteration of breast cancer cells in the process of tumor-associated macrophages-promoted metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-11.
HBEGF <sup>+</sup> macrophages in rheumatoid arthritis induce fibroblast invasiveness
Authors: David Kuo, Jennifer Ding, Ian S. Cohn, Fan Zhang, Kevin Wei, Deepak A. Rao, Cristina Rozo, Upneet K. Sokhi, Sara Shanaj, David J. Oliver, Adriana P. Echeverria, Edward F. DiCarlo, Michael B. Brenner, Vivian P. Bykerk, Susan M. Goodman, Soumya Raychaudhuri, Gunnar Rätsch, Lionel B. Ivashkiv, Laura T. Donlin
Journal: Science Translational Medicine (2019)

Macrophages promote fibroblast invasiveness and demonstrate variable response to anti-inflammatory medications in patients with rheumatoid arthritis.
Opioids: new toolkit aims to help GPs manage long term use
Authors: Elisabeth Mahase
Journal: BMJ (2019)

GPs must act urgently to taper or reduce dosages of opioids for patients with long term prescriptions, researchers have said.1

The call to action came from researchers at the University of East Anglia, who have created a new toolkit to help GPs do this. Its recommendations were based on research evidence and the experiences of healthcare organisations and doctors.

If GPs are expected to reduce patients’ dependence on opioids they must have the skills to …
Proteomic test for anti-PD-1 checkpoint blockade treatment of metastatic melanoma with and without BRAF mutations
Authors: Paolo A. Ascierto, Mariaelena Capone, Antonio M. Grimaldi, Domenico Mallardo, Ester Simeone, Gabriele Madonna, Heinrich Roder, Krista Meyer, Senait Asmellash, Carlos Oliveira, Joanna Roder, Julia Grigorieva
Journal: Journal for ImmunoTherapy of Cancer (2019)

The therapeutic landscape in metastatic melanoma has changed dramatically in the last decade, with the success of immune checkpoint inhibitors resulting in durable responses for a large number of patients. For patients with <i>BRAF</i> mutations, combinations of BRAF and MEK inhibitors demonstrated response rates and benefit comparable to those from immune checkpoint inhibitors, providing the rationale for sequential treatment with targeted and immunotherapies and raising the question of optimal treatment sequencing. Biomarkers for the selection of anti-PD-1 therapy in <i>BRAF</i> wild type (<i>BRAF</i> WT) and in <i>BRAF</i> mutated (<i>BRAF</i> MUT) patients help development of alternative treatments for patients unlikely to benefit, and might lead to better understanding of the interaction of checkpoint inhibition and targeted therapy. In this paper we evaluate the performance of a previously developed serum proteomic test, BDX008, in metastatic melanoma patients treated with anti-PD-1 agents and investigate the role of <i>BRAF</i> mutation status. BDX008, a pre-treatment proteomic test associated with acute phase reactants, wound healing and complement activation, stratifies patients into two groups, BDX008+ and BDX008-, with better and worse outcomes on immunotherapy. Serum samples were available from 71 patients treated with anti-PD1 inhibitors; 25 patients had <i>BRAF</i> mutations, 39 were wild type. Overall, BDX008+ patients had significantly better overall survival (OS) (HR = 0.50, <i>P</i> = 0.016) and a trend for better progression-free survival (PFS) (HR = 0.61, <i>P</i> = 0.060) than BDX008- patients. BDX008 classification was statistically significant in the analyses adjusted for mutation status, LDH, and line of treatment (<i>P</i> = 0.009 for OS and 0.031 for PFS). <i>BRAF</i> WT BDX008+ patients had markedly long median OS of 32.5 months and 53% landmark 2 years survival, with statistically significantly superior OS as compared to BDX008- patients (HR = 0.41, <i>P</i> = 0.032). The difference between BDX008+ and BDX008- in PFS in <i>BRAF</i> WT patients and in OS and PFS in <i>BRAF</i> MUT patients did not reach statistical significance, though numerically was consistent with overall results. The test demonstrated significant interaction with neutrophil-to-lymphocyte ratio (NLR) (PFS <i>P</i> = 0.041, OS <i>P</i> = 0.004). BDX008 as a biomarker selecting for benefit from immune checkpoint blockade, especially in patients with wild type <i>BRAF</i> and in subgroups with low NLR<i>,</i> warrants further evaluation.
Abstract P4-07-02: Withdrawn
Authors: BS Katzenellenbogen, VS Guillen, Y Ziegler, SH Kim, MJ Laws, Y Zhao, MA Yasuda, Z Li, D El-Ashry, JA Katzenellenbogen
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Katzenellenbogen BS, Guillen VS, Ziegler Y, Kim SH, Laws MJ, Zhao Y, Yasuda MA, Li Z, El-Ashry D, Katzenellenbogen JA. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-07-02.
Dual‐Specificity Tyrosine Phosphorylation–Regulated Kinase 3 Loss Activates Purine Metabolism and Promotes Hepatocellular Carcinoma Progression
Authors: Fei Ma, Yuekun Zhu, Xing Liu, Qingxin Zhou, Xuehui Hong, Chao Qu, Xing Feng, Yiyun Zhang, Qingbin Ding, Jiabao Zhao, Jingjing Hou, Mengya Zhong, Huiqin Zhuo, Lifeng Zhong, Zhijian Ye, Wen Xie, Yu Liu, Yubo Xiong, Hongwei Chen, Daxun Piao, Bei Sun, Zhi Gao, Qinghua Li, Zhen Zhang, Xingfeng Qiu, Zhiyong Zhang
Journal: Hepatology (2019)

Cancer cells metabolize different energy sources to generate biomass rapidly. The purine biosynthetic pathway was recently identified as an important source of metabolic intermediates for these processes. However, very little was known about the regulatory mechanisms of purine metabolism in hepatocellular carcinoma (HCC). We explored the role of dual‐specificity tyrosine (Y) phosphorylation–regulated kinase 3 (Dyrk3) in HCC metabolism. Dyrk3 was significantly down‐regulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis of metabolites suggests that the effect of Dyrk3 on HCC occurred at least partially through down‐regulating purine metabolism, as evidenced by the fact that inhibiting purine synthesis reverted the HCC progression mediated by the loss of Dyrk3. We further provide evidence that this action of Dyrk3 knockdown requires nuclear receptor coactivator 3 (NCOA3), which has been shown to be a coactivator of activating transcription factor 4 (ATF4) to target purine pathway genes for transcriptional activation. Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser‐1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity. However, the phosphorylation‐resistant NCOA3‐S1330A mutant has the opposite effect. Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double‐negative feedback loop. Importantly, levels of Dyrk3 and phospho‐NCOA3‐S1330 inversely correlate with the expression of ATF4 in human HCC specimens. Conclusion : Our findings not only illustrate a function of Dyrk3 in reprograming HCC metabolism by negatively regulating NCOA3/ATF4 transcription factor complex but also identify NCOA3 as a phosphorylation substrate of Dyrk3, suggesting the Dyrk3/NCOA3/ATF4 axis as a potential candidate for HCC therapy.
Clare Gerada: The older doctor
Authors: Clare Gerada
Journal: BMJ (2019)

I am at that age where increasing numbers of my friends are becoming grandparents. They talk of their joy at this new role—and about how caring for children seems easier this time around.

Grandparents are there to offer support, wisdom (preferably in small amounts), and the knowledge they have gleaned from “having done it before.” They know how to accept the anxiety of the unknown and to deal with the fear of “getting it wrong.” This resonates with me—not yet as a grandparent but as an older member of my profession.

When doctors reach a certain age …
Abstract 512: Gene expression profiling reveals tumor immunobiological differences in prostate cancer between African-American and European-American men
Authors: Tiffany A Wallace, Robyn L Prueitt, Ming Yi, Robert M Stephens, Stefan Ambs
Journal: Cancer Research (2008)

Abstract The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed 162 transcripts to be differentially expressed between African-American and European-American prostate cancer patients at a false discovery rate of 5% or less. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differentially expressed genes clustering in immune response, defense response, antigen presentation, B-cell/T-cell function, cytokine signaling, and inflammatory response pathways. Most commonly, the genes involved in these pathways were more highly expressed in tumors of African-American patients when compared with those of European-American patients. Amongst the immune-specific genes over-expressed by African-American patients was indoleamine 2,3-dioxygenease, HLA-E, and HLA-G. All three of these genes are well-known contributors of immunologic tolerance in tumors. Furthermore, a distinctive interferon signature was identified in the African-American prostate tumors, suggesting the possibility of viral involvement in disease etiology in this African-American population. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups.
Abstract P3-03-03: Sentinel node biopsy (SNB) vs Low axillary sampling (LAS) in predicting nodal status of post-chemotherapy axilla in women with breast cancer
Authors: V Parmar, NS Nair, V Vanamali, RW Hawaldar, S Siddique, T Shet, SB Desai, V Rangarajan, A Patil, S Gupta, RA Badwe
Journal: Cancer Research (2019)

Abstract Introduction There is no safe method of avoiding complete axillary lymph node dissection in women with breast cancer after neo-adjuvant chemotherapy. sentinel node biopsy (SNB) has had prohibitively high false negative rate. We tested low axillary sampling (LAS) and SNB performed in same patient to predict axillary lymph node status in clinically node negative women undergoing breast conservation or modified radical mastectomy after neo-adjuvant chemotherapy. Methodology Post neo-adjuvant chemotherapy 751 women who had no palpable axillary lymph node underwent LAS (all lymph nodes below intercosto-brachial nerve). Of these 751 women, 730 also underwent SNB by dual technique after injection of blue dye as well as radio-isotope. SN was identified within and outside axillary sampling specimen. SN as well as LAS specimens were distinctly examined for nodal metastasis. The rest of the axillary dissection was completed in all patients. Post NACT 292/751(38.9%) had residual positive lymph nodes on pathology. The identification rate, false negative rate (FNR), and negative predictive value (NPV) of SNB and LAS were compared for predicting negative axillary lymph node status. Results The median clinical tumor size was 5cm (1-15cm) and 533(71%) patients were N1 or N2 at presentation. The SNB identification rate was 87.1% (636 of 730), with a median of 5 nodes and node positive in 238 of 636 (37.4%). LAS identification rate was 98% (736 of 751), with a median of 7 nodes and node positive in 292 of 736 (39.6%). In all but one case, the SN was found within the LAS specimen. The FNR of SNB (blue, hot and adjacent palpable nodes) was 19.7% (47 of 238, one sided 95% upper CI 24.0) compared to LAS with FNR of 9.9% (29 of 292, one-sided 95% upper CI 12.8) (p&amp;lt;0.001). Comparative NPV for SNB and LAS were 89.4% and 93.9% respectively. If SNB was confined to blue/hot node excluding adjacent palpable nodes, FNR was 31.6% (74 of 234, 95% upper CI 36.6). Conclusions LAS is superior to SNB in identification rate, FNR and NPV in predicting node negative axilla post-neoadjuvant chemotherapy. LAS can be safely used to predict negative axilla with less than 10% chance of leaving residual disease. Citation Format: Parmar V, Nair NS, Vanamali V, Hawaldar RW, Siddique S, Shet T, Desai SB, Rangarajan V, Patil A, Gupta S, Badwe RA. Sentinel node biopsy (SNB) vs Low axillary sampling (LAS) in predicting nodal status of post-chemotherapy axilla in women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-03.