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Rapid identification of pathogenic bacteria using Raman spectroscopy and deep learning
Raman optical spectroscopy promises label-free bacterial detection, identification, and antibiotic susceptibility testing in a single step. However, achieving clinically relevant speeds and accuracies remains challenging due to weak Raman signal from bacterial cells and numerous bacterial species and phenotypes. Here we generate an extensive dataset of bacterial Raman spectra and apply deep learning approaches to accurately identify 30 common bacterial pathogens. Even on low signal-to-noise spectra, we achieve average isolate-level accuracies exceeding 82% and antibiotic treatment identification accuracies of 97.0±0.3%. We also show that this approach distinguishes between methicillin-resistant and -susceptible isolates of Staphylococcus aureus (MRSA and MSSA) with 89±0.1% accuracy. We validate our results on clinical isolates from 50 patients. Using just 10 bacterial spectra from each patient isolate, we achieve treatment identification accuracies of 99.7%. Our approach has potential for culture-free pathogen identification and antibiotic susceptibility testing, and could be readily extended for diagnostics on blood, urine, and sputum.
Journal Article
Next generation systematics
\"We live in an age of ubiquitous genomics. Next generation sequencing (NGS) technology, both widely adopted today and advancing at pace, has transformed today's data landscape, opening up an enormous source of heritable characters to the comparative biologist. Its impact on systematics, like many other fields of biology, has been felt throughout its breadth: from defining species boundaries to estimating their evolutionary histories. This volume examines the broad range of ways in which NGS data are being used in systematics and in the fields that it underpins, from biodiversity prospecting to evo-devo. The authors draw on contemporary case studies to demonstrate state-of-the-art applications of NGS data. These, along with novel analyses, comprehensive reviews and lively perspectives are combined to produce an authoritative account of contemporary issues in systematics that have been advanced and impacted by the recent adoption of NGS\"-- Provided by publisher.
Book
Social class in Europe
This timely volume introduces a new social class schema, the European Socio-economic Classification (ESeC), which has been specifically developed and tested for use in EU comparative research. Social Class in Europe aims to introduce researchers to the new classification and its research potential. Since socio-economic classifications are so widely used in official and academic research, this collection is essential reading for all users of both government and academic social classifications. While primarily aimed at researchers who will be using the ESeC, the book’s contents will also have a wider appeal as it is suitable for students taking substantive courses in European studies or as a supplementary text for undergraduates studying the EU, Sociology and Economics. Because of its inherent methodological interest, the book should prove a valuable tool for undergraduate and graduate courses that discuss how social scientists construct and validate basic measures. It will also be required reading for policy makers and analysts concerned with social inequality and social exclusion across Europe.
eBook
Cells of the adult human heart
Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.
Journal Article
33 Molecular subtype diagnosis of endometrial carcinoma: comparison of NGS panel and promise classifier
Objectives The molecular classification of endometrial carcinoma (EC) is taking the diagnosis on EC to a more comprehensive level and will aid to better identify those patients whose disease is likely to behave differently than predicted when using traditional risk stratification. We are transitioning towards the use of molecular classification in a clinical context; however, it remains undetermined, which would be the optimal approach. Methods In this study,s we characterized patients (n=60) whose disease had a different than anticipated clinical course determined by current risk stratification tools and histomorphologically corresponding control samples. The aim was to access the molecular classification using two different methods; by performing the FoundationOne CDx NGS panel and using the ProMisE classifier and performing immunohistochemical stainings for MMR proteins and p53. POLE mutation status was in both settings derived from FoundationOne results. Results 64 patients were entered in this study, and in 60 cases, the molecular classification was successful. MSI status was available from 53 cases. Tumour molecular subtype was of prognostic significance and showed the expected correlations with grade and histotype. Molecular subtype diagnosis based on NGS and ProMisE was in complete agreement for 50 of 53 tumors. In 2 tumors, a TP53 mutation was detected on NGS, but immunostaining showed subclonal pattern, and 1 case was MSI based on NGS but MMR deficient by immunohistochemistry. Conclusions Both NGS panel sequencing of formalin-fixed paraffin embedded endometrial carcinomas and molecular subtype diagnosis based primarily on immunostaining (ProMisE) yield identical results in 94.3% (kappa – 0.91) of cases.
Journal Article
4 Refining pathologic interpretation of endometrial carcinomas: lessons learned from a nationwide study in a new era of molecular classification
ObjectivesMolecular classification of endometrial carcinoma (EC) enables consistent classification of tumours and provides valuable prognostic and predictive information. Herein we describe molecular subtype distribution and histomorphologic correlates in recently diagnosed (2016) ECs from across Canada.MethodsMolecular classification was performed on representative tumour specimens from participating centres. Clinicopathologic, management and outcome data were collected (REDCap).Results1453 ECs from 30 centres have been identified. Complete molecular (ProMisE) and outcome data is reportable for 862 patients. Histologic and clinicopathologic parameters associated with molecular subtype and are summarised in table 1. Amongst participating centres, routine testing of MMR and p53 immunohistochemistry (IHC) was performed in only 23.5% (range 3.5–80.0% per centre) and 15% (2.2–45.7%) of cases respectively. We found p53 abn ECs across a range of histotypes, including low grade endometrioid EC. Subclonal p53 staining was observed in 3.9% of cases and significantly associated with the presence of pathogenic POLE mutations (p≤0.001). Subclonal MMR IHC expression was seen in 3.5% of cases and has previously been shown to occur predominantly in the context of MLH1 hypermethylation. MMRd was significantly associated with LVI (p <0.001). ProMisE subtype was significantly associated with clinical outcomes (p<0.001) even in low stage disease [OS p=0.045, DSS p=0.009, PFS p=0.005 for stage I].Abstract 4 Table 1Univariable association of clinicopathologic characteristics by proactive molecular risk classifier for endometrial cancer (ProMisE) subtypeConclusionsObservation of unusual or unexpected p53 and MMR IHC staining patterns and associated clinical implications highlight the importance of routine testing of these parameters in ECs.
Journal Article