Combining clustering and classification ensembles: A novel pipeline to identify breast cancer profiles

Breast Cancer is one of the most common causes of cancer death in women, representing a very complex disease with varied molecular alterations. To assist breast cancer prognosis, the classification of patients into biological groups is of great significance for treatment strategies. Recent studies have used an ensemble of multiple clustering algorithms to elucidate the most characteristic biological groups of breast cancer. However, the combination of various clustering methods resulted in a number of patients remaining unclustered. Therefore, a framework still needs to be developed which can assign as many unclustered (i.e. biologically diverse) patients to one of the identified groups in order to improve classification. Therefore, in this paper we develop a novel classification framework which introduces a new ensemble classification stage after the ensemble clustering stage to target the unclustered patients. Thus, a step-by-step pipeline is introduced which couples ensemble clustering with ensemble classification for the identification of core groups, data distribution in them and improvement in final classification results by targeting the unclustered data. The proposed pipeline is employed on a novel real world breast cancer dataset and subsequently its robustness and stability are examined by testing it on standard datasets. The results show that by using the presented framework, an improved classification is obtained. Finally, the results have been verified using statistical tests, visualisation techniques, cluster quality assessment and interpretation from clinical experts

The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer

Purpose: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity, and patient outcome. Glutamine availability for growth and progression of BC is important in several BC subtypes. This study aimed to evaluate the biological and prognostic role of the combined expression of key glutamine transporters, SLC1A5, SLC7A5 and SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC1A5, SLC7A5 and SLC3A2 were assessed at the protein level, using immunohistochemistry on tissue microarrays constructed from a large well characterised BC cohort (n=2,248). Patients were stratified into accredited clusters based on protein expression and correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: Clustering analysis of SLC1A5, SLC7A5 and SLC3A2 identified three clusters Low SLCs (SLC1A5-/SLC7A5-/SLC3A2-), High SLC1A5 (SLC1A5+/SLC7A5-/SLC3A2-) and High SLCs (SLC1A5+/SLC7A5+/SLC3A2+) which had distinct correlations to known prognostic factors and patient outcome (p<0.001). The key regulator of tumour cell metabolism, c-MYC, was significantly expressed in tumours in the High SLCs cluster (p<0.001). When different BC subtypes were considered, the association with the poor outcome was observed in the ER+ high proliferation/luminal B class only (p= 0.003). In multivariate analysis, SLC clusters were independent risk factor for shorter breast cancer specific survival (p= 0.001). Conclusion: The co-operative expression of SLC1A5, SLC7A5 and SLC3A2 appears to play a role in the aggressive subclass of ER+ high proliferation/ luminal BC, driven by c-MYC, and therefore have the potential to act as therapeutic targets, particularly in synergism

Growth and survival of prawn (Macrobrachium tenellum) in experimental cultures during summer and autumn in the tropical Mexican Pacific coast [Crecimiento y supervivencia del langostino (macrobrachium tenellum) en cultivos experimentales de verano y oto�o en la costa tropical del pac�fico mexicano]

For aquaculture purposes, Macrobrachium tenellum is considered as a good candidate, is not aggressive nor presents cannibalism and can tolerate an ample interval of temperatures, salinities and oxygen concentrations. The present work evaluates the semi-intensive culture of M. tenellum under environmental conditions of summer and autumn with special attention to water temperature. The results of the experimental cultures in the tropical Mexican Pacific coast, suggest this species demonstrates better growth during the end of the spring, summer and the beginning of the autumn, time at which the average temperature of the water is near 30�C. The experimental cultures of end of autumn and beginnings of winter demonstrate minimum growth, with an average temperature of the culture water of 27�C. Other parameters like pH, O 2 concentration and turbidity in the culture water were similar in all the experimental cultures reason why temperature is suggested the factor was the determinant in the differences found in growth

Growth and survival of prawn (Macrobrachium tenellum) in experimental cultures during summer and autumn in the tropical Mexican Pacific coast [Crecimiento y supervivencia del langostino (macrobrachium tenellum) en cultivos experimentales de verano y otoño en la costa tropical del pacífico mexicano]

For aquaculture purposes, Macrobrachium tenellum is considered as a good candidate, is not aggressive nor presents cannibalism and can tolerate an ample interval of temperatures, salinities and oxygen concentrations. The present work evaluates the semi-intensive culture of M. tenellum under environmental conditions of summer and autumn with special attention to water temperature. The results of the experimental cultures in the tropical Mexican Pacific coast, suggest this species demonstrates better growth during the end of the spring, summer and the beginning of the autumn, time at which the average temperature of the water is near 30°C. The experimental cultures of end of autumn and beginnings of winter demonstrate minimum growth, with an average temperature of the culture water of 27°C. Other parameters like pH, O 2 concentration and turbidity in the culture water were similar in all the experimental cultures reason why temperature is suggested the factor was the determinant in the differences found in growth

Corncob arabinoxylan for new materials

Limited data exist on the costs of care of patients with multiple sclerosis (MS) in low- to middle-income nations. The purpose of this study was to describe the economic burden associated with care of Mexican patients with relapsing-remitting MS in a representative sample of the largest institution of the Mexican public healthcare system. We analysed individual data of 492 patients (67 % women) with relapsing-remitting MS registered from January 2009 to February 2011 at the Mexican Social Security Institute. Direct costs were measured about the use of diagnostic tests, disease-modifying therapies (DMTs), symptoms control, medical consultations, relapses, intensive care and rehabilitation. Four groups were defined according to DMT alternatives: (1) interferon beta (IFN?)-1a, 6 million units (MU); (2) IFN?-1a, 12MU; (3) IFN?-1b, 8MU; and (4) glatiramer acetate. All patients received DMTs for at least 1 year. The most frequently used DMT was glatiramer acetate (45.5 %), followed by IFN?-1a 12MU (22.6 %), IFN?-1b 8MU (20.7 %), and IFN?-1a 6MU (11.2 %). The mean cost of a specialised medical consultation was 74.90 (US $107.00). A single relapse had a mean total cost of 2,505.97 (US$3,579.96). No differences were found in annualised relapse rates and costs of relapses according to DMT. However, a significant difference was observed in total annual costs according to treatment groups (glatiramer acetate being the most expensive), mainly due to differences in unitary costs of alternatives. From the public institutional perspective, when equipotent DMTs are used in patients with comparable characteristics, the costs of DMTs largely determine the total expenses associated with care of patients with relapsing-remitting MS in a middle-income country. " 2013 Belgian Neurological Society.",,,,,,"10.1007/s13760-013-0200-z",,,"http://hdl.handle.net/20.500.12104/40401","http://www.scopus.com/inward/record.url?eid=2-s2.0-84891647794&partnerID=40&md5=e91c85bf23b6b1d7624a3e6ea4d31f69",,,,,,"4",,"Acta Neurologica Belgica",,"41

Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series

The Nottingham Prognostic Index Plus (NPI+)is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cyto-keratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI-like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer’s V and their role in patient outcome prediction using Kaplan–Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p>0.01). The biological classes were significantly associated with patient outcome (p0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER- tumours and the poor PG in the Luminal N class (p>0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER- classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted