tbuckley/cabot-search huggingface dataset:
Immunomarker Support Vector Machine Classifier for Prediction of Gastric Cancer Survival and Adjuvant Chemotherapeutic Benefit
Authors: Yuming Jiang, Jingjing Xie, Zhen Han, Wei Liu, Sujuan Xi, Lei Huang, Weicai Huang, Tian Lin, Liying Zhao, Yanfeng Hu, Jiang Yu, Qi Zhang, Tuanjie Li, Shirong Cai, Guoxin Li
Journal: Clinical Cancer Research (2018)

Purpose: Current tumor-node-metastasis (TNM) staging system cannot provide adequate information for prediction of prognosis and chemotherapeutic benefits. We constructed a classifier to predict prognosis and identify a subset of patients who can benefit from adjuvant chemotherapy.Experimental Design: We detected expression of 15 immunohistochemistry (IHC) features in tumors from 251 gastric cancer (GC) patients and evaluated the association of their expression level with overall survival (OS) and disease-free survival (DFS). Then, integrating multiple clinicopathologic features and IHC features, we used support vector machine (SVM)-based methods to develop a prognostic classifier (GC-SVM classifier) with features. Further validation of the GC-SVM classifier was performed in two validation cohorts of 535 patients.Results: The GC-SVM classifier integrated patient sex, carcinoembryonic antigen, lymph node metastasis, and the protein expression level of eight features, including CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, CD57IM, CD66bIM, CD68CT, and CD34. Significant differences were found between the high- and low-GC-SVM patients in 5-year OS and DFS in training and validation cohorts. Multivariate analysis revealed that the GC-SVM classifier was an independent prognostic factor. The classifier had higher predictive accuracy for OS and DFS than TNM stage and can complement the prognostic value of the TNM staging system. Further analysis revealed that stage II and III GC patients with high-GC-SVM were likely to benefit from adjuvant chemotherapy.Conclusions: The newly developed GC-SVM classifier was a powerful predictor of OS and DFS. Moreover, the GC-SVM classifier could predict which patients with stage II and III GC benefit from adjuvant chemotherapy. Clin Cancer Res; 24(22); 5574-84. ©2018 AACR.
Deletion of Angiotensin II Type 2 Receptor Exaggerated Atherosclerosis in Apolipoprotein E–Null Mice
Authors: MasaruIwai, RuiChen, ZhenLi, TetsuyaShiuchi, JunSuzuki, AyumiIde, MasahiroTsuda, MidoriOkumura, Li-JuanMin, MasakiMogi, MasatsuguHoriuchi
Journal: Circulation (2005)

Background— The role of angiotensin II (Ang II) type 2 (AT2) receptor in atherosclerosis was explored with the use of AT2 receptor/apolipoprotein E (ApoE)–double-knockout (AT2/ApoE-DKO) mice, with a focus on oxidative stress. Methods and Results— After treatment with a high-cholesterol diet (1.25% cholesterol) for 10 weeks, ApoE-knockout (KO) mice developed atherosclerotic lesions in the aorta. In AT2/ApoE-DKO mice receiving a high-cholesterol diet, the atherosclerotic changes were further exaggerated, without significant changes in plasma cholesterol level and blood pressure. In the atherosclerotic lesion, an increase in superoxide production, NADPH oxidase activity, and expression of p47phox was observed. These changes were also greater in AT2/ApoE-DKO mice. An Ang II type 1 (AT1) receptor blocker, valsartan, inhibited atherosclerotic lesion formation, superoxide production, NADPH oxidase activity, and p47phox expression; these inhibitory effects were significantly weaker in AT2/ApoE-KO mice. We further...
Overexpression of hypoxia-inducible factor HIF-1α predicts early relapse in breast cancer : a retrospective study in a series of 745 patients.
Authors: Colette Taranger-Charpin, Jean-Philippe Dales, Christophe Picard, Monique Silvy, Stéphane Garcia, Marie-Noelle Lavaut, Claude Allasia, Pascal Bonnier, Jean Gabert
Journal: Cancer Research (2005)

488   HIF-1 is a heterodimeric transcriptional activator composed of HIF-1α and HIF-1β subunits, which are basic helix-loop-helix-PAS domain proteins. HIF-1 is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. The biological activity of HIF-1 is determined by the expression and activity of the HIF-1α subunit which is mainly regulated by oxygen-dependant posttranslational modifications. Moreover, HIF-1α expression seems to be regulated at least in part by mRNA alternative splicing. HIF-1α overexpression has been shown in a variety of human cancers, but only few studies have documented the prognostic relevance of HIF-1α protein expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1α expression on prognosis in a large series (n=745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1α expression was investigated using immunohistochemical assays on frozen sections. HIF-1α protein expression was correlated with patients’ outcome (median follow-up, 13.5 years) and with HIF-1α isoforms expression evaluated by real-time quantitative PCR method. Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1α protein expression (cutoff = 10%) significantly correlated with poor overall survival (p=0.019). HIF-1α expression correlated with high metastasis risk among the whole group of patients (p=0.008). Multivariate analysis (Cox model) revealed that the HIF-1α predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1α protein expression was also significantly predictive of metastasis risk (p=0.03) and of relapse (p=0.035). Correlation between HIF-1α protein detection and expression of HIF-1α splice variants in tumors is also discussed. These data suggest that HIF-1α is associated with a worse prognosis in patients with invasive breast carcinoma.
Child health guidelines in the era of sustainable development goals
Authors: Jonathon L Simon, Bernadette Daelmans, Cynthia Boschi-Pinto, Samira Aboubaker, Wilson Were
Journal: BMJ (2018)

Child health guidelines must broaden in scope beyond under 5 mortality to facilitate improvements in child health and development necessary to meet the 2030 sustainable development goals, say <b>Jonathon L Simon and colleagues</b>
Abstract 16127: Adenosine-kinase Inhibition Improves Conducted Coronary Arteriole Dilation in HFpEF Patients
Authors: Alec Davila, Huijuan Dou, Yuqing Huo, Vijay Patel, Neal Weintraub, Zsolt Bagi
Journal: Circulation (2016)

With alarmingly growing incidence (1% increase/year among heart failure patients) and mortality rate (5.2% annual death) heart failure with preserved ejection fraction (HFpEF) commonly develops due...
Tissue‐Resident Memory <scp>CD</scp>8+ T Cells Acting as Mediators of Salivary Gland Damage in a Murine Model of Sjögren's Syndrome
Authors: Cai‐Yue Gao, Yuan Yao, Liang Li, Shu‐Han Yang, Hui Chu, Koichi Tsuneyama, Xiao‐Mei Li, M. Eric Gershwin, Zhe‐Xiong Lian
Journal: Arthritis & Rheumatology (2018)

Although a role for CD4+ T cells in the pathogenesis of Sjögren's syndrome (SS) has been documented, the pathogenic significance of CD8+ T cells is unclear. The aim of this study was to investigate the role of CD8+ T cells in the development of SS.Flow cytometry and immunofluorescence analyses were utilized to detect T cell infiltration within the labial salivary glands of patients with primary SS. In parallel, p40-/- CD25-/- mice were used as a murine model of SS. In addition, mice with genetic knockout of CD4, CD8a, or interferon-γ (IFNγ) were crossed with p40-/- CD25-/- mice to study the pathogenic significance of specific lineage subpopulations, including functional salivary gland tests as well as histopathologic and serologic data. A CD8+ T cell-specific depletion antibody was used in this murine SS model to evaluate its potential as a therapeutic strategy.CD8+ T cells with a tissue-resident memory phenotype outnumbered CD4+ T cells in the labial salivary glands of patients with SS, and were primarily colocalized with salivary duct epithelial cells and acinar cells. Furthermore, infiltrating CD8+ T cells with a CD69+CD103+/- tissue-resident phenotype and with a significant elevation of IFNγ production were dominant in the submandibular glands of mice in this murine SS model. CD8a knockout abrogated the development of SS in these mice. Knockout of IFNγ decreased CD8+ T cell infiltration and gland destruction. More importantly, depletion of CD8+ T cells fully protected mice against the pathologic manifestations of SS, even after the onset of disease.These data reveal the pathogenic significance of CD8+ T cells in the development and progression of SS in the salivary glands. Treatment directed against CD8+ T cells may be a rational therapy for the management of SS in human subjects.
Active Electrodes for Wearable EEG Acquisition : Review and Design Methodology
Authors: J. Xu, Srinjoy Mitra, Chris Van Hoof, Refet Firat Yazicioglu, K.A.A. Makinwa
Journal: IEEE Reviews in Biomedical Engineering (2017)

Active electrodes (AEs), i.e., electrodes with built-in readout circuitry, are increasingly being implemented in wearable healthcare and lifestyle applications due to AEs' robustness to environmental interference. An AE locally amplifies and buffers μV-level EEG signals before driving any cabling. The low output impedance of an AE mitigates cable motion artifacts, thus enabling the use of high-impedance dry electrodes for greater user comfort. However, developing a wearable EEG system, with medical grade signal quality on noise, electrode offset tolerance, common-mode rejection ratio, input impedance, and power dissipation, remains a challenging task. This paper reviews state-of-the-art bio-amplifier architectures and low-power analog circuits design techniques intended for wearable EEG acquisition, with a special focus on an AE system interfaced with dry electrodes.
Abstract 20082: High Prevalence, Poor Awareness and Suboptimal Treatment and Control of Hypertension in North and South India.
Authors: Sailesh Mohan, Prashant Jarhyan, Shreeparna Ghosh, Nikhil Sv, Balaji Gummidi, Bhaskara Rao, Nikhil Tandon, K.Srinath Reddy, Dorairaj Prabhakaran
Journal: Circulation (2016)

Introduction:  Hypertension is the major driver of the escalating cardiovascular epidemic in India accounting for 10% of all deaths. Despite its high burden, hypertension prevention and control is suboptimal.   Methods:  We conducted a representative population based cross-sectional survey, among 12243 participants aged ≥30 years, to determine the prevalence, awareness, treatment and control of hypertension in epidemiologically transitioning rural and urban areas of North (Sonipat, Haryana) and South (Visakhapatnam, Andhra Pradesh) India. Participants were selected using a multistage cluster random sampling technique. Data were obtained using an interviewer administered questionnaire, anthropometry and bio sample collection. Hypertension and cardiovascular risk factors were measured using standard definitions and protocols. Age-standardized estimates were calculated using the WHO standard population.   Results:  The mean age was 47.7(SD± 12.5) years. Age-standardized prevalence of hypertension was 28.2% [95% CI: 27.4-29.0] in this large sample. Among those with hypertension, awareness rate was 40.4% [38.5-42.3], treatment rate was 36.3% [34.5-38.2] and control rate was 20.3% [18.8-21.9]. There were wide rural-urban [rural: 22.3% (21.3-23.3), urban: 34.5% (33.3-35.6)] and gender differences [men: 29.9% (28.7-31.1), women: 27.2% (26.1-28.2)] in the prevalence of hypertension. The awareness [men: 33.3% (30.9-35.6); women: 48.3% (45.3-51.2)], treatment [men: 28.7% (26.6-30.9), women: 44.8% (41.9-47.7)] and control [men: 15.8% (14.1-17.6), women: 25.6% (23.1-28.3)] rates were higher in women compared with men. In the regression analysis, younger age, male gender, urban residence, lesser education, depression, high waist circumference, current tobacco and alcohol use were associated with poor control of hypertension.   Conclusions:  In transitioning communities in India the burden of hypertension is high and its management suboptimal. Context specific public health measures to improve the prevention and management are warranted to improve vascular health of the population and reduce death and disability associated with uncontrolled hypertension.
We should eat freshly cooked meals
Authors: Carlos Augusto Monteiro, Geoffrey Cannon, Jean-Claude Moubarac, Renata Bertazzi Levy, Maria Laura Louzada, Patrícia Constante Jaime
Journal: BMJ (2018)

The BMJ ’s introduction to its series on the science and politics of nutrition states: “More articles are planned.”1 We have two concerns that should guide further articles.

Firstly, all but one of the series’ leading authors are based in the United States or United Kingdom. Dietary patterns and food systems in these countries are now largely based on snacking and ready to consume …
Regulatory T cells as a therapeutic target in psoriasis
Authors: I.S. Kotb, B.J. Lewis, R.N. Barker, A.D. Ormerod
Journal: British Journal of Dermatology (2018)

Psoriasis is a common condition that affects the skin and joints. Skin psoriasis tends to wax and wane throughout life without obvious reasons, and thus causes considerable distress. Someone with psoriasis may have other family members with the same problem but this is not usually the case. In psoriasis, more skin cells are made leading to build‐up on the top layer and formation of flaky patches on the skin or severe dandruff of the scalp. The cause is unknown and believed to involve the genes and immune system, and the treatments we use now can control psoriasis but don't cure it. This study from Aberdeen, UK looked into two types of cells of the immune system; one of them can start or cause psoriasis to happen, while the other has the power to fight back and calm down the skin. We tested the effect of certain injections, cream and light which we frequently use to treat psoriasis, on those cells by taking blood and skin samples. We found that the skin became better after six weeks. The light made the numbers of the “good” cells go higher, while the injection caused the “bad” cells to become fewer and had no effect on the “good” cells. The cream increased the “good” cells and reduced the “bad” cells. We noticed these changes in both the blood and skin which means that the cream and light can have an effect on cells in the circulation and this can be used in the future to make new and safer treatments.
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells
Authors: Otto Kauko, Caitlin M. O’Connor, Evgeny Kulesskiy, Jaya Sangodkar, Anna Aakula, Sudeh Izadmehr, Laxman Yetukuri, Bhagwan Yadav, Artur Padzik, Teemu Daniel Laajala, Pekka Haapaniemi, Majid Momeny, Taru Varila, Michael Ohlmeyer, Tero Aittokallio, Krister Wennerberg, Goutham Narla, Jukka Westermarck
Journal: Science Translational Medicine (2018)

Pharmacological PP2A activation is a druggable approach to overcome MEK inhibitor resistance.
IMbrave150: A randomized phase III study of 1L atezolizumab plus bevacizumab vs sorafenib in locally advanced or metastatic hepatocellular carcinoma.
Authors: Richard S. Finn, Michel Ducreux, Shukui Qin, Peter R. Galle, Andrew X. Zhu, Masafumi Ikeda, Tae-You Kim, Derek-Zhen Xu, Wendy Verret, Juan Liu, William Grossman, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2018)

TPS4141 Background: Hepatocellular carcinoma (HCC) is a lethal disease with the highest mortality-to-incidence ratio of any solid tumor. The current standard of care for 1L treatment of patients (pts) with locally advanced or metastatic HCC is sorafenib (sor), a multikinase inhibitor. Single-agent treatment involving inhibition of PD-L1/PD-1 immune checkpoint or VEGF has shown modest activity in HCC. Evidence from a Phase I study (Stein ASCO 2018, submitted) in HCC supports a strong scientific rationale for combining atezolizumab (atezo; anti–PD-L1) with bevacizumab (bev; anti-VEGF) to achieve greater clinical benefit. In addition to its anti-angiogenic activity, bev may have immunomodulatory effects in the tumor microenvironment (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors) that can potentially increase the efficacy of atezo in inhibiting PD-L1/PD-1 signaling and restoring anti-tumor T-cell activity. Methods: IMbrave150 (YO40245) is a Phase III, open-label, multicenter, randomized study to evaluate atezo + bev vs sor in pts with locally advanced or metastatic and/or unresectable HCC. Eligible pts will be naive to prior systemic therapy for HCC, have ≥ 1 measurable untreated lesion (per RECIST v1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts with bleeding or high risk for bleeding with untreated varices will be excluded. Randomization will be stratified by region (Asia [excluding Japan] vs rest of world), macrovascular invasion and/or extrahepatic spread (presence vs absence), baseline α-fetoprotein level ( < 400 vs ≥ 400 ng/mL) and ECOG PS (0 vs 1). Pts will be randomized 2:1 to receive atezo (1200 mg) plus bev (15 mg/kg) IV Q3W or sor (400 mg) PO BID until loss of clinical benefit or unacceptable toxicity. No crossover will be allowed. Co-primary and secondary efficacy endpoints are listed in Table. ≈ 480 pts are planned to be enrolled globally. Clinical trial information: NCT03434379.Efficacy endpoints. Co-primary ORR (investigator [INV]-assessed per RECIST v1.1), OS Secondary PFS, DOR, TTP (INV-assessed per RECIST v1.1) ORR, PFS, DOR, TTP (independent review facility (IRF)-assessed per RECIST v1.1) ORR, PFS, DOR, TTP (IRF-assessed per HCC mRECIST)
Nuclear magnetic resonance‐based metabolomics identifies phenylalanine as a novel predictor of incident heart failure hospitalisation: results from PROSPER and FINRISK 1997
Authors: Christian Delles, Naomi J. Rankin, Charles Boachie, Alex McConnachie, Ian Ford, Antti Kangas, Pasi Soininen, Stella Trompet, Simon P. Mooijaart, J. Wouter Jukema, Faiez Zannad, Mika Ala‐Korpela, Veikko Salomaa, Aki S. Havulinna, Paul Welsh, Peter Würtz, Naveed Sattar
Journal: European Journal of Heart Failure (2017)

We investigated the association between quantified metabolite, lipid and lipoprotein measures and incident heart failure hospitalisation (HFH) in the elderly, and examined whether circulating metabolic measures improve HFH prediction.Overall, 80 metabolic measures from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were measured by proton nuclear magnetic resonance spectroscopy (n = 5341; 182 HFH events during 2.7-year follow-up). We repeated the work in FINRISK 1997 (n = 7330; 133 HFH events during 5-year follow-up). In PROSPER, the circulating concentrations of 13 metabolic measures were found to be significantly different in those who were later hospitalised for heart failure after correction for multiple comparisons. These included creatinine, phenylalanine, glycoprotein acetyls, 3-hydroxybutyrate, and various high-density lipoprotein measures. In Cox models, two metabolites were associated with risk of HFH after adjustment for clinical risk factors and N-terminal pro-B-type natriuretic peptide (NT-proBNP): phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10-1.53; P = 0.002] and acetate (HR 0.81, 95% CI 0.68-0.98; P = 0.026). Both were retained in the final model after backward elimination. Compared to a model with established risk factors and NT-proBNP, this model did not improve the C-index but did improve the overall continuous net reclassification index (NRI 0.21; 95% CI 0.06-0.35; P = 0.007) due to improvement in classification of non-cases (NRI 0.14; 95% CI 0.12-0.17; P < 0.001). Phenylalanine was replicated as a predictor of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03-1.48; P = 0.023).Our findings identify phenylalanine as a novel predictor of incident HFH, although prediction gains are low. Further mechanistic studies appear warranted.
Unsuspected Metastases to Muscles in Osteosarcoma Detected on 18F-Sodium Fluoride PET-CT
Authors: Sharjeel Usmani, Fahad Marafi, Rashid Rasheed, David Bakiratharajan, Muneera Al Maraghy, Fareeda Al Kandari
Journal: Clinical Nuclear Medicine (2018)

Metastasis of osteosarcoma to the muscles is extremely rare. F-sodium fluoride (NaF) is a bone-seeking agent that can also localize extraosseous calcifying lesions. We report the case of a 33-year-old woman with osteosarcoma of the right fibula treated with surgery and chemotherapy 2 years back who was referred for F-NaF PET-CT to evaluate possible metastatic lesions. F-NaF PET-CT unexpectedly detected 2 foci of soft tissue increased tracer uptake in the right lateral abdominal and left paraspinal muscles, which corresponded to the focal calcification in the muscles. The pathological examination revealed metastatic osteosarcoma to the muscles.
User experience of instant blood pressure: exploring reasons for the popularity of an inaccurate mobile health app
Authors: Timothy B. Plante, Anna C. O’Kelly, Bruno Urrea, Zane T. MacFarlane, Roger S. Blumenthal, Jeanne Charleston, Edgar R. Miller, Lawrence J. Appel, Seth S. Martin
Journal: npj Digital Medicine (2018)

Instant blood pressure (IBP) is a top-selling yet inaccurate blood pressure (BP)-measuring app that underreports elevated BP. Its iTunes app store user ratings and reviews were generally positive. Whether underreporting of elevated BP improves user experience is unknown. Participants enrolled at five clinics estimated their BP, measured their BP with IBP, then completed a user experience survey. Participants were grouped based on how their IBP BP measurements compared to their estimated BP (IBP Lower, IBP Similar, or IBP Higher). Logistic regressions compared odds of rating "agree" or "strongly agree" on survey questions by group. Most participants enjoyed using the app. In the adjusted model, IBP Higher had significantly lower proportions reporting enjoyment and motivation to check BP in the future than IBP Similar. All three groups were comparable in perceived accuracy of IBP and most participants perceived it to be accurate. However, user enjoyment and likelihood of future BP monitoring were negatively associated with higher-than-expected reported systolic BP. These data suggest reassuring app results from an inaccurate BP-measuring app may have improved user experience, which may have led to more positive user reviews and greater sales. Systematic underreporting of elevated BPs may have been a contributor to the app's success. Further studies are needed to confirm whether falsely reassuring output from other mobile health apps improve user experience and drives uptake.