tbuckley/cabot-search huggingface dataset:
Myocardial strain computed at multiple spatial scales from tagged magnetic resonance imaging: Estimating cardiac biomarkers for CRT patients
Authors: Matthew Sinclair, Devis Peressutti, Esther Puyol-Antón, Wenjia Bai, Simone Rivolo, Jessica Webb, Simon Claridge, Thomas Jackson, David Nordsletten, Myrianthi Hadjicharalambous, Eric Kerfoot, Christopher A. Rinaldi, Daniel Rueckert, Andrew P. King
Journal: Medical Image Analysis (2017)

Abnormal cardiac motion can indicate different forms of disease, which can manifest at different spatial scales in the myocardium. Many studies have sought to characterise particular motion abnormalities associated with specific diseases, and to utilise motion information to improve diagnoses. However, the importance of spatial scale in the analysis of cardiac deformation has not been extensively investigated. We build on recent work on the analysis of myocardial strains at different spatial scales using a cardiac motion atlas to find the optimal scales for estimating different cardiac biomarkers. We apply a multi-scale strain analysis to a 43 patient cohort of cardiac resynchronisation therapy (CRT) patients using tagged magnetic resonance imaging data for (1) predicting response to CRT, (2) identifying septal flash, (3) estimating QRS duration, and (4) identifying the presence of ischaemia. A repeated, stratified cross-validation is used to demonstrate the importance of spatial scale in our analysis, revealing different optimal spatial scales for the estimation of different biomarkers.
Scotland to clamp down on junk food promotion in order to tackle obesity
Authors: Bryan Christie
Journal: BMJ (2017)

Action is being planned in Scotland to restrict supermarkets promoting unhealthy foods as part of a series of measures aimed at reducing obesity levels.

The Scottish government is also calling on the UK parliament to ban broadcasters advertising foods high in fat, sugar, and salt at times when they can be seen by children. If this is unsuccessful, Scotland will seek such powers to be devolved to the Scottish parliament.

The plans are set out in a consultation document1 …
A retrospective study of effectiveness and safety of Nivolmab for advanced or recurrent NSCLC harboring EGFR mutation
Authors: Yuki Akazawa, Masahide Mori, Takako Inoue, Toru Kumagai, Akito Hata, Nobuyuki Katakami, Yoshiko Urata, Takashi Nishimura, Takashi Yokoi, Shunichi Negoro
Journal: Annals of Oncology (2017)
Pembrolizumab in patients (pts) with PD-L1–positive (PD-L1<sup>+</sup>) advanced ovarian cancer: Updated analysis of KEYNOTE-028.
Authors: Andrea Varga, Sarina Anne Piha-Paul, Patrick Alexander Ott, Janice M. Mehnert, Dominique Berton-Rigaud, Anne Morosky, Guo Qing Zhao, Reshma A. Rangwala, Daniela Matei
Journal: Journal of Clinical Oncology (2017)

5513 Background: Overexpression of the PD-1 ligand PD-L1 has been demonstrated in ovarian cancer and may hinder an effective antitumor immune response. A preliminary analysis of the ovarian cancer cohort of the KEYNOTE-028 study (NCT02054806) suggested that the PD-1 inhibitor pembrolizumab has promising antitumor activity in pts with PD-L1 + advanced ovarian cancer. An updated analysis of the ovarian cancer cohort based on 15.5 months of follow-up is presented. Methods: Key eligibility criteria for the ovarian cohort of this nonrandomized, multicohort phase Ib trial were advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of prior therapy; PD-L1 positivity defined as membranous staining on ≥1% of tumor and associated inflammatory cells or positive staining in stroma; and ECOG PS 0/1. Pembrolizumab (10 mg/kg every 2 wk) was given for ≤2 y or until confirmed progression/unacceptable toxicity. Response was assessed per RECIST v1.1 by investigators every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end points were safety, tolerability, and confirmed ORR. Results: 26 pts (median age, 57.5 y) were enrolled; 61.5% were white, 38.5% received ≥5 therapies for recurrent/metastatic disease, and 53.8% received prior neoadjuvant/adjuvant therapies. As of the October 10, 2016, data cutoff, the median follow-up duration was 15.5 mo (range, 2.4-30.8 mo). 1 pt had a complete response and 2 had partial responses; 6 pts had stable disease as best response. ORR was 11.5% (95% CI, 2.4%-30.2%). Tumor reduction was observed in 6/26 (23.1%); all 3 patients who responded completed 2 years of treatment. Median duration of response was not reached (range, 24.9+ to 26.5+ mo). Median (95% CI) PFS and OS were 1.9 mo (1.8-3.2 mo) and 13.1 mo (6.7-17.5 mo) respectively. Treatment-related AEs occurred in 73.1% of pts, and the most common were arthralgia (19.2%), nausea (15.4%), pruritus (15.4%), rash (11.5%), and diarrhea (11.5%). 1 patient had a grade 3 drug-related adverse event (transaminase increased). Conclusions: With 15.5 mo of follow-up, pembrolizumab continued to be well tolerated and demonstrated durable antitumor activity in pts with advanced ovarian cancer. Clinical trial information: NCT02054806.
TCT-391 Comparision of CHAD2DS2VASc score vs GRACE score predicting value in the long term all-cause mortality in patients with st elevation myocardial infarction who undergoing primary percutaneous coronary
Authors: Alfredo Redondo Diéguez, Ramiro Trillo Nouche, Alejandro Avila Carrillo, Diego Lopez Otero
Journal: Journal of the American College of Cardiology (2017)
Distinct Patterns of Autoantibodies Against G-Protein–Coupled Receptors in Chagas' Cardiomyopathy and Megacolon
Authors: Silvia Gilka Muñoz Saravia, Annekathrin Haberland, Sabine Bartel, Raul Araujo, Gregorio Valda, Diana Duchen, Ivan Diaz Ramirez, Adrian Constantin Borges, Gerd Wallukat, Ingolf Schimke
Journal: Journal of the American College of Cardiology (2010)
Infographic: physical activity for pregnant women
Authors: Ralph Smith, Hamish Reid, Anne Matthews, Catherine Calderwood, Marian Knight, Charlie Foster
Journal: British Journal of Sports Medicine (2017)

Our recent BJSM editorial petitioned for ‘a time for action’ regarding physical activity (PA) and pregnancy guidance in the UK.1 We highlighted that despite pregnancy providing a unique opportunity to promote PA behaviour change,2 healthcare professionals (HPs) lack the confidence, knowledge and resources to deliver appropriate PA advice. They feel under-resourced, uncertain regarding safety concerns and inadequately trained.3 Consequently, despite being receptive to PA advice, pregnant women receive inconsistent, vague and conflicting guidance.4 These issues may contribute to reduced levels of PA during pregnancy, leaving few women meeting the recommended activity levels.5 



The 2011 UK Chief Medical Officers’ (CMO) PA recommendations led to the development of a series …
A Population of Heterogeneous Breast Cancer Patient-Derived Xenografts Demonstrate Broad Activity of PARP Inhibitor in BRCA1/2 Wild-Type Tumors
Authors: Kurt W. Evans, Erkan Yuca, Argun Akcakanat, Stephen M. Scott, Natalia Paez Arango, Xiaofeng Zheng, Ken Chen, Coya Tapia, Emily Tarco, Agda K. Eterovic, Dalliah M. Black, Jennifer K. Litton, Timothy A. Yap, Debu Tripathy, Gordon B. Mills, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2017)

Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed. Phenotypic profiling was performed by determining efficacy of a panel of standard and investigational agents.Results: Twenty-six PDXs were developed from 25 patients. Twenty-two were generated from residual disease following neoadjuvant chemotherapy, and 24 were from triple-negative breast cancer (TNBC). These PDXs harbored a heterogeneous set of genomic alterations and represented all TNBC molecular subtypes. On RPPA, PDXs varied in extent of PI3K and MAPK activation. PDXs also varied in their sensitivity to chemotherapeutic agents. PI3K, mTOR, and MEK inhibitors repressed growth but did not cause tumor regression. The PARP inhibitor talazoparib caused dramatic regression in five of 12 PDXs. Notably, four of five talazoparib-sensitive models did not harbor germline BRCA1/2 mutations, but several had somatic alterations in homologous repair pathways, including ATM deletion and BRCA2 alterations.Conclusions: PDXs capture the molecular and phenotypic heterogeneity of TNBC. Here we show that PARP inhibition can have activity beyond germline BRCA1/2 altered tumors, causing regression in a variety of molecular subtypes. These models represent an opportunity for the discovery of rational combinations with targeted therapies and predictive biomarkers. Clin Cancer Res; 23(21); 6468-77. ©2017 AACR.
Quantitative Imaging for Targeted Radionuclide Therapy Dosimetry - Technical Review
Authors: Tiantian Li, Edwin C. I. Ao, Bieke Lambert, Boudewijn Brans, Stefaan Vandenberghe, Greta S. P. Mok
Journal: Theranostics (2017)

Targeted radionuclide therapy (TRT) is a promising technique for cancer therapy.However, in order to deliver the required dose to the tumor, minimize potential toxicity in normal organs, as well as monitor therapeutic effects, it is important to assess the individualized internal dosimetry based on patient-specific data.Advanced imaging techniques, especially radionuclide imaging, can be used to determine the spatial distribution of administered tracers for calculating the organ-absorbed dose.While planar scintigraphy is still the mainstream imaging method, SPECT, PET and bremsstrahlung imaging have promising properties to improve accuracy in quantification.This article reviews the basic principles of TRT and discusses the latest development in radionuclide imaging techniques for different theranostic agents, with emphasis on their potential to improve personalized TRT dosimetry.
Antitumor activity of ASP8273 300 mg in subjects with EGFR mutation-positive non-small cell lung cancer: Interim results from an ongoing phase 1 study.
Authors: Helena Alexandra Yu, Alexander I. Spira, Leora Horn, Jared Weiss, Howard Jack West, Giuseppe Giaccone, Tracey L. Evans, Ronan Joseph Kelly, Bhardwaj B. Desai, Andrew Krivoshik, Tanya E. Fleege, Srinivasu Poondru, Fei Jie, Kouji Aoyama, Debbie Ann Whitcomb, Anne Therese Keating, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2016)

9050 Background: ASP8273 is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that selectively and irreversibly inhibits EGFR mutations (eg, exon 19 deletions, L858R), including the secondary resistance mutation T790M. Prior analyses of an ongoing open-label study estimated the ASP8273 recommended Phase 2 dose (RP2D) as 300 mg orally QD. Described here are the preliminary antitumor effects of the RP2D in EGFR mutation-positive non-small cell lung cancer (NSCLC) previously treated with an EGFR TKI (most patients received ≥ 1 prior treatment) in 2 study populations: all subjects and subjects with T790M. Methods: Subjects ( ≥ 18 yr) were enrolled into a dose-escalation (25–500 mg), response-expansion (100–400 mg), RP2D (300 mg), or food effect (300 mg) cohort of an ongoing study (NCT02113813) conducted in the United States. Antitumor activity for all subjects was assessed based on RECIST 1.1. Response and progression-free survival (PFS) were determined for all subjects treated with ASP8273 300 mg and for a subset of subjects harboring the T790M mutation. Results: As of January 04, 2016, 60 subjects (15 M/45 F) had been treated with ASP8273 300 mg without reports of dose-limiting toxicities in the dose-escalation (n = 7), response-expansion (n = 18), RP2D (n = 19), or food-effect (n = 16) cohorts. All patients were EGFR mutation-positive with 90% having a T790M mutation (14 M/40 F). For the 45 subjects treated with ASP8273 300 mg with evaluable data, disease control rate (DCR) was 62% (n = 28/45); 16 subjects achieved a partial response (PR) and 12 subjects achieved durable stable disease (SD). For the 40 T790M+ subjects with evaluable data, DCR was 65% (n = 26/40); 15 subjects showed PR and 11 subjects had durable SD. Preliminary median PFS for all subjects treated with ASP8273 300 mg (n = 60, 21 of which were non-censored events) was 6.7 months (95% CI: 4.11–9.79 months); median PFS for T790M+ subjects treated with ASP8273 300 mg (n = 54, 18 of which were non-censored events) was 6.7 months (95% CI: 5.32–9.79 months). Conclusions: ASP8273 at 300 mg QD demonstrated robust antitumor activity in subjects with pre-treated EGFR mutation-positive NSCLC and the T790M mutation. Clinical trial information: NCT02113813.
Northern Ireland trainees are well supported and supervised, GMC finds
Authors: Abi Rimmer
Journal: BMJ (2017)

Trainee doctors in Northern Ireland feel well supported and well supervised and enjoy their clinical training placements, the General Medical Council has found.

Between February and April this year the GMC visited all five integrated health and social care trusts in Northern Ireland, as well as Queen’s University Belfast. In a report of its findings the GMC said that the overall experience of the trainees it met across the trusts was a positive one.1 “They mostly felt …
PRMT5 as a druggable target for glioblastoma therapy
Authors: Yeshavanth Kumar Banasavadi-Siddegowda, Alessandra M Welker, Min An, Xiaozhi Yang, Wei Zhou, Guqin Shi, Jaime Imitola, Chenglong Li, Sigmund Hsu, Jiang Wang, Mitch Phelps, Jianying Zhang, Christine E Beattie, Robert Baiocchi, Balveen Kaur
Journal: Neuro-Oncology (2017)

In spite of standard multimodal therapy consisting of surgical resection followed by radiation and concurrent chemotherapy, prognosis for glioblastoma (GBM) patients remains poor. The identification of both differentiated and undifferentiated "stem cell like" populations in the tumor highlights the significance of finding novel targets that affect the heterogeneous tumor cell population. Protein arginine methyltransferase 5 (PRMT5) is one such candidate gene whose nuclear expression correlates with poor survival and has been reported to be required for survival of differentiated GBM cells and self-renewal of undifferentiated GBM cells. In the current study we screened the specificity and efficacy of 4 novel PRMT5 inhibitors in the treatment of GBM. Efficacies of these inhibitors were screened using an in vitro GBM neurosphere model and an in vivo intracranial zebrafish model of glioma. Standard molecular biology methods were employed to investigate changes in cell cycle, growth, and senescence. In vitro and in vivo studies revealed that among the 4 PRMT5 inhibitors, treatment of GBM cells with compound 5 (CMP5) mirrored the effects of PRMT5 knockdown wherein it led to apoptosis of differentiated GBM cells and drove undifferentiated primary patient derived GBM cells into a nonreplicative senescent state. In vivo antitumor efficacy combined with the specificity of CMP5 underscores the importance of developing it for translation.
TCT-494 Long term prognostic impact of myocardium at risk and CTO presence in the setting of myocardial infarction complicated by out-of-hospital cardiac arrest
Authors: Nikolaos Magkoutis, Sebastian Voicu, Demetris Yannopoulos, Jean Guillaume Dillinger, Damien Logeart, Patrick Henry, Georgios Sideris
Journal: Journal of the American College of Cardiology (2017)
Integrating DNA Methylation and Hydroxymethylation Data with the Mint Pipeline
Authors: Raymond G. Cavalcante, Snehal Patil, Yongseok Park, Laura S. Rozek, Maureen A. Sartor
Journal: Cancer Research (2017)

Abstract DNA methylation (5mC) plays important roles in mammalian development, oncogenesis, treatment response, and responses to the environment. DNA hydroxymethylation (5hmC) is also an informative epigenetic mark with distinct roles in regulation and cancer. Gold-standard, widely used technologies (bisulfite conversion, followed by deep sequencing) cannot distinguish between 5mC and 5hmC. Therefore, additional experiments are required to differentiate the two marks, and in silico methods are needed to analyze, integrate, and interpret these data. We developed the Methylation INTegration (mint) pipeline to support the comprehensive analysis of bisulfite conversion and immunoprecipitation-based methylation and hydroxymethylation assays, with additional steps toward integration, visualization, and interpretation. The pipeline is available as both a command line and a Galaxy graphical user interface tool. Both implementations require minimal configuration while remaining flexible to experiment specific needs. Cancer Res; 77(21); e27–30. ©2017 AACR.
PS02.22 Alectinib Following Prior ALK Tyrosine Kinase Inhibitor (TKI) Therapy: Results from the US Expanded Access Program (EAP)
Authors: J.D. Patel, S.M. Gadgeel, S.I. Ou, A. Le Maitre, M. Schulz, S. Liu, A. Zeaiter, B. Balas, R. Gupta, A. Shaw
Journal: Journal of Thoracic Oncology (2017)
PS02.11 Is There any Cardiotoxicity with Anti-PD/PDL 1 Immunotherapy? A Meta-Analysis of Randomized Clinical Trials
Authors: M. Rahouma, M. Baudo, M. Yahia, M. Kamel, G. Ghaly, A.A. Abouarab, N. Abdel Karim, A. Mohamed, M. Gaudino
Journal: Journal of Thoracic Oncology (2017)
Abstract 14321: Severity of Chronic Kidney Disease Correlates With the Prevalence of Left Atrial Low-voltage Areas
Authors: Yasuhiro Matsuda, Masaharu Masuda, Masashi Fujita, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kinonori Nanto, Takashi Kanda, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, Koji Yanaka, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Masaaki Uematsu
Journal: Circulation (2016)

Introduction:  The presence of left atrial low-voltage areas (LVA) has been shown to be strongly associated with atrial fibrillation recurrence after pulmonary vein isolation. A preliminary study has shown concomitant chronic kidney disease (CKD) increased the rate of recurrence of atrial fibrillation. However the association between CKD and LVA presence are not fully determined.   Hypothesis:  The severity of CKD correlates with the prevalence of left atrial LVA.   Methods:  This study included 183 patients who underwent the initial ablation for atrial fibrillation (age, 67 ± 9 years old; male, 134 (73%) patients; persistent atrial fibrillation, 82 (45%) patients). LVA was defined as sites of the left atrial electrogram amplitude   Results:  Of 183 patients, 76 (42%) patients had LVA. Patients with LVA demonstrated lower eGFR calculated by cystatin C (73.8±21.9 versus 86.2±23.9 ml/min/1.73m 2 , P  2 , P =0.01). Receiver operating characteristic curve analysis revealed that eGFR calculated by cystatin C was a better predictor of LVA presence than that by creatine (area under the curve, 0.669 versus 0.617). LVA existed more frequently in patients with more severe categories of CKD (Figure). The optimal cut-off value of eGFR calculated by cystatin C was 71.5ml/min/1.73m 2  corresponded to 79.4% sensitivity, 50.0% specificity and 67.2% predictive accuracy. In the multivariate analysis, independent predictors of LVA presence were eGFR 2  (odds ratio (OR) 2.8 [95% confidence interval (CI) 1.3-6.1], P =0.012) and high age (OR 1.05 [95% CI 1.01-1.10], P =0.028).   Conclusions:  The severity of CKD correlates with left atrial LVA prevalence in patients with atrial fibrillation undergoing catheter ablation.
Brote de parotiditis asociado a una baja eficacia de la vacuna - Oporto, Portugal, 1996
Authors: G Gonçalves, A de Araújo, M. L. Monteiro Cardoso
Journal: Eurosurveillance (1998)

En Portugal, la vacunacion contra la parotiditis comenzo en 1987 con la introduccion de la vacuna combinada contra el sarampion, la parotiditis y la rubeola (SPR) en el programa nacional de vacunacion (Programa Nacional de Vacinacao: PNV) para ninos de ambos sexos a los 15 meses de edad. En noviembre de 1990, se anadio al PNV una segunda dosis de SPR a los 11-13 anos de edad. En octubre de 1992, las reacciones adversas atribuidas a la cepa del virus de la parotiditis presente en la vacuna utilizada (Urabe Am9) llevo al Ministerio de Sanidad portugues a reemplazarla por otra vacuna SPR conteniendo la cepa viral Rubini. En octubre de 1992, comenzo a distribuirse en Oporto y en sus centros sanitarios municipales el primer lote de esta ‘nueva’ vacuna.
Exacerbation risk and characterisation of the UK’s asthma population from infants to old age
Authors: Chloe I Bloom, Francis Nissen, Ian J Douglas, Liam Smeeth, Paul Cullinan, Jennifer K Quint
Journal: Thorax (2017)

Few studies have examined the characteristics of a general asthma population; most have focused on more severe patients or severe exacerbations.This population-based cohort study, from April 2007 to September 2015, used linked primary and secondary care electronic healthcare records (Clinical Practice Research Datalink, Hospital Episode Statistics). Characteristics of four age cohorts, 'Under 5s', '5 to 17s', '18 to 54s', '55+', were described. Exacerbation risk factors, including asthma severity (measured by the British Thoracic Society (BTS) stepwise approach), were assessed using Poisson regression.424 326 patients with current asthma were eligible (n, median follow-up: 'Under 5s'=17 320, 1 year; '5 to 17s'=82 707, 3.3 years; '18 to 54s'=210 724, 4 years; '55+'=113 575, 5.1 years). Over 60% of the total study population had mild asthma (BTS steps 1/2). There were differences between the cohort's characteristics, including by gender, disease severity and exacerbation pattern. The rate of exacerbations was highest in the oldest cohort and lowest in the '5 to 17s' cohort (rate per 10 person-years (95% CI), 'Under 5s'=4.27 (4.18 to 4.38), '5 to 17s'=1.48 (1.47 to 1.50), '18 to 54s'=3.22 (3.21 to 3.24), '55+'=9.40 (9.37 to 9.42)). In all cohorts, exacerbation rates increased with increasing asthma severity, after adjusting for confounders including gender, socioeconomic status, smoking, body mass index, atopy, rhinitis, gastro-oesophageal reflux, anxiety, depression and COPD.The majority of UK patients with asthma had mild asthma and did not experience an exacerbation during follow-up. Patients aged ≥55 years had the lowest proportion with mild asthma and highest rate of exacerbations; the opposite was found in patients aged between 5 and 18 years.
Biodegradable Core-shell Dual-Metal-Organic-Frameworks Nanotheranostic Agent for Multiple Imaging Guided Combination Cancer Therapy
Authors: Dongdong Wang, Jiajia Zhou, Ruohong Shi, Huihui Wu, Ruhui Chen, Beichen Duan, Guoliang Xia, Pengping Xu, Hui Wang, Shu Zhou, Chengming Wang, Haibao Wang, Zhen Guo, Qianwang Chen
Journal: Theranostics (2017)

Metal-organic-frameworks (MOFs) possess high porosity, large surface area, and tunable functionality are promising candidates for synchronous diagnosis and therapy in cancer treatment. Although large number of MOFs has been discovered, conventional MOF-based nanoplatforms are mainly limited to the sole MOF source with sole functionality. In this study, surfactant modified Prussian blue (PB) core coated by compact ZIF-8 shell (core-shell dual-MOFs, CSD-MOFs) has been reported through a versatile stepwise approach. With Prussian blue as core, CSD-MOFs are able to serve as both magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) agents. We show that CSD-MOFs crystals loading the anticancer drug doxorubicin (DOX) are efficient pH and near-infrared (NIR) dual-stimuli responsive drug delivery vehicles. After the degradation of ZIF-8, simultaneous NIR irradiation to the inner PB MOFs continuously generate heat that kill cancer cells. Their efficacy on HeLa cancer cell lines is higher compared with the respective single treatment modality, achieving synergistic chemo-thermal therapy efficacy.