In this primer, we give a review of the inverse problem for EEG source localization. This is intended for the researchers new in the field to get insight in the state-of-the-art techniques used to find approximate solutions of the brain sources giving rise to a scalp potential recording. Furthermore, a review of the performance results of the different techniques is provided to compare these different inverse solutions. The authors also include the results of a Monte-Carlo analysis which they performed to compare four non parametric algorithms and hence contribute to what is presently recorded in the literature. An extensive list of references to the work of other researchers is also provided.This paper starts off with a mathematical description of the inverse problem and proceeds to discuss the two main categories of methods which were developed to solve the EEG inverse problem, mainly the non parametric and parametric methods. The main difference between the two is to whether a fixed number of dipoles is assumed a priori or not. Various techniques falling within these categories are described including minimum norm estimates and their generalizations, LORETA, sLORETA, VARETA, S-MAP, ST-MAP, Backus-Gilbert, LAURA, Shrinking LORETA FOCUSS (SLF), SSLOFO and ALF for non parametric methods and beamforming techniques, BESA, subspace techniques such as MUSIC and methods derived from it, FINES, simulated annealing and computational intelligence algorithms for parametric methods. From a review of the performance of these techniques as documented in the literature, one could conclude that in most cases the LORETA solution gives satisfactory results. In situations involving clusters of dipoles, higher resolution algorithms such as MUSIC or FINES are however preferred. Imposing reliable biophysical and psychological constraints, as done by LAURA has given superior results. The Monte-Carlo analysis performed, comparing WMN, LORETA, sLORETA and SLF, for different noise levels and different simulated source depths has shown that for single source localization, regularized sLORETA gives the best solution in terms of both localization error and ghost sources. Furthermore the computationally intensive solution given by SLF was not found to give any additional benefits under such simulated conditions.

Coastal areas are quite fragile landscapes as they are among the most vulnerable to climate change and natural hazards. Coastline mapping and change detection are essential for safe navigation, resource management, environmental protection, and sustainable coastal development and planning. In this paper, we proposed a new methodology for the automatic extraction of coastline, using aerial images. This method is based on edge detection and active contours (snake method). Initially the noise of the image is reduced which is followed by an image segmentation. The output images are further processed to remove all small spatial objects and to concentrate on the spatial objects of interests. Then, the morphological operators are applied. We used aerial images taken from an aircraft and high-resolution satellite images from a coastal area in Crete, Greece, and we compared the results with geodetic measurements, to validate the methodology.

Osteoarthritis (OA) is a multi-factorial disease leading progressively to loss of articular cartilage and subsequently to loss of joint function. While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis. Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. We analyzed the proteome of chondrocytes using high resolution mass spectrometry and quantified it by label-free quantification and western blot analysis. We also used WebGestalt, a web-based enrichment tool for the functional annotation and pathway analysis of the differentially synthesized proteins, using the Wikipathways database. ClueGO, a Cytoscape plug-in, is also used to compare groups of proteins and to visualize the functionally organized Gene Ontology (GO) terms and pathways in the form of dynamical network structures. The proteomic analysis led to the identification of a total of ~2400 proteins. 269 of them showed differential synthesis levels between the two groups. Using functional annotation, we found that proteins belonging to pathways associated with regulation of the actin cytoskeleton, EGF/EGFR, TGF-β, MAPK signaling, integrin-mediated cell adhesion, and lipid metabolism were significantly enriched in the OA samples (p ≤10−5). We also observed that the proteins GSTP1, PLS3, MYOF, HSD17B12, PRDX2, APCS, PLA2G2A SERPINH1/HSP47 and MVP, show distinct synthesis levels, characteristic for OA or control chondrocytes. In this study we compared the quantitative changes in proteins synthesized in osteoarthritic compared to normal chondrocytes. We identified several pathways and proteins to be associated with OA chondrocytes. This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype.

Breast cancer is the most common cancer in women worldwide. It is the most frequently diagnosed cancer among women in 140 countries out of 184 reporting countries. Lesions of breast cancer are abnormal areas in the breast tissues. Various types of breast cancer lesions include (1) microcalcifications, (2) masses, (3) architectural distortion, and (4) bilateral asymmetry. Microcalcification can be classified as benign, malignant, and benign without a callback. In the present manuscript, we propose an automatic pipeline for the detection of various categories of microcalcification. We performed deep learning using convolution neural networks (CNNs) for the automatic detection and classification of all three categories of microcalcification. CNN was applied using four different optimizers (ADAM, ADAGrad, ADADelta, and RMSProp). The input images of a size of 299 × 299 × 3, with fully connected RELU and SoftMax output activation functions, were utilized in this study. The feature map was obtained using the pretrained InceptionResNetV2 model. The performance evaluation of our classification scheme was tested on a curated breast imaging subset of the DDSM mammogram dataset (CBIS–DDSM), and the results were expressed in terms of sensitivity, specificity, accuracy, and area under the curve (AUC). Our proposed classification scheme outperforms the ability of previously used deep learning approaches and classical machine learning schemes.

Circulating tumor cells (CTCs) are important for metastatic dissemination of cancer. They can provide useful information, regarding biological features and tumor heterogeneity; however, their detection and characterization are difficult due to their limited number in the bloodstream and their mesenchymal characteristics. Therefore, new biomarkers are needed to address these questions. Bioinformatics functional enrichment analysis revealed a subgroup of 24 genes, potentially overexpressed in CTCs. Among these genes, the chemokine receptor CXCR4 plays a central role. After prioritization according to the CXCR4 corresponding pathways, five molecules (JUNB, YWHAB, TYROBP, NFYA, and PRDX1) were selected for further analysis in biological samples. The SKBR3, MDA-MB231, and MCF7 cell lines, as well as PBMCs from normal (n = 10) blood donors, were used as controls to define the expression pattern of all the examined molecules. Consequently, 100 previously untreated metastatic breast cancer (mBC) patients (n = 100) were analyzed using the following combinations of antibodies: CK (cytokeratin)/CXCR4/JUNB, CK/NFYA/ΥWHΑΒ (14-3-3), and CK/TYROBP/PRDX1. A threshold value for every molecule was considered the mean expression in normal PBMCs. Quantification of CXCR4 revealed overexpression of the receptor in SKBR3 and in CTCs, following the subsequent scale (SKBR3>CTCs>Hela>MCF7>MDA-MB231). JUNB was also overexpressed in CTCs (SKBR3>CTCs>MCF7>MDA-MB231>Hela). According to the defined threshold for each molecule, CXCR4-positive CTCs were identified in 90% of the patients with detectable tumor cells in their blood. In addition, 65%, 75%, 14.3%, and 12.5% of the patients harbored JUNB-, TYROBP-, NFYA-, and PRDX-positive CTCs, respectively. Conversely, none of the patients revealed YWHAB-positive CTCs. Interestingly, JUNB expression in CTCs was phenotypically and statistically enhanced compared to patients’ blood cells (p = 0.002) providing a possible new biomarker for CTCs. Furthermore, the detection of JUNB-positive CTCs in patients was associated with poorer PFS (p = 0.015) and OS (p = 0.002). Moreover, JUNB staining of 11 primary and 4 metastatic tumors from the same cohort of patients revealed a dramatic increase of JUNB expression in metastasis. CXCR4, JUNB, and TYROBP were overexpressed in CTCs, but only the expression of JUNB was associated with poor prognosis, providing a new biomarker and a potential therapeutic target for the elimination of CTCs.

Epilepsy is one of the most common brain diseases, characterized by frequent recurrent seizures or “ictal” states. A patient experiences uncontrollable muscular contractions, inducing loss of mobility and balance, which may result in injury or even death during these ictal states. Extensive investigation is vital to establish a systematic approach for predicting and informing patients about oncoming seizures ahead of time. Most methodologies developed are focused on the detection of abnormalities using mostly electroencephalogram (EEG) recordings. In this regard, research has indicated that certain pre-ictal alterations in the Autonomic Nervous System (ANS) can be detected in patient electrocardiogram (ECG) signals. The latter could potentially provide the basis for a robust seizure prediction approach. The recently proposed ECG-based seizure warning systems utilize machine learning models to classify a patient’s condition. Such approaches require the incorporation of large, diverse, and thoroughly annotated ECG datasets, limiting their application potential. In this work, we investigate anomaly detection models in a patient-specific context with low supervision requirements. Specifically, we consider One-Class SVM (OCSVM), Minimum Covariance Determinant (MCD) Estimator, and Local Outlier Factor (LOF) models to quantify the novelty or abnormality of pre-ictal short-term (2–3 min) Heart Rate Variability (HRV) features of patients, trained on a reference interval considered to contain stable heart rate as the only form of supervision. Our models are evaluated against labels that were either hand-picked or automatically generated (weak labels) by a two-phase clustering procedure for samples of the “Post-Ictal Heart Rate Oscillations in Partial Epilepsy” (PIHROPE) dataset recorded by the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, achieving detection in 9 out of 10 cases, with average AUCs of over 93% across all models and warning times ranging from 6 to 30 min prior to seizure. The proposed anomaly detection and monitoring approach can potentially pave the way for early detection and warning of seizure incidents based on body sensor inputs.