BCN20000: dermoscopic lesions in the wild

This article summarizes the BCN20000 dataset, composed of 19424 dermoscopic images of skin lesions captured from 2010 to 2016 in the facilities of the Hospital Clínic in Barcelona. With this dataset, we aim to study the problem of unconstrained classification of dermoscopic images of skin cancer, including lesions found in hard-to-diagnose locations (nails and mucosa), large lesions which do not fit in the aperture of the dermoscopy device, and hypo-pigmented lesions. The BCN20000 will be provided to the participants of the ISIC Challenge 2019 [8], where they will be asked to train algorithms to classify dermoscopic images of skin cancer automatically.Peer ReviewedPreprin

ESTIMATING DIELECTRIC PROPERTIES OF BIOLOGICAL TISSUE

INTRODUCTION Microwave imaging has been of interest in recent decades, offering the potential of an affordable and non-ionizing medical diagnostic modality. This technique is sensitive to changes in dielectric properties such as permittivity and conductivity. One approach is microwave radar imaging, which creates images by focusing signals caused by reflections at material interfaces. In order to improve the images from radar approaches, patient-specific dielectric property estimations have been used to determine the speed of wave travel within the tissue [1]. Estimating dielectric properties of biological tissue can also be useful in emerging quantitative applications including bone health assessment. Methods such as local rod probes and antenna measurements of planar samples have been developed to estimate dielectric properties, but are of limited use for in vivo measurements. We have previously developed methods of permittivity estimation with a custom antenna, however this approach requires two measurements at different separation distances and is unable to estimate conductivity. This study aims to improve on methods of estimating permittivity and to add an estimate of conductivity of in vivo biological tissue by incorporating an antenna calibration method. METHODS In order to remove the influence of the antennas on measurements, a previously developed calibration method [2] was adapted to be used with a custom ultra-wideband antenna system [3], allowing permittivity and conductivity to be estimated over a range of frequencies. The two antennas are characterized as 2x2 matrices at each frequency, determined from two calibration measurements: the first is performed with the antennas separated by an electrical conductor, and the second measurement is done with the antennas in direct contact with one another. Measurements were performed using a vector network analyzer (Agilent, PNA-L, N5230A), and take less than 15 seconds. Measurement samples were placed between the two antennas, with their surfaces in contact with the entire antenna aperture. Dielectric properties were then estimated using the magnitude and phase of the calibrated transmission data. To validate this method, dielectric properties of several liquids were estimated and compared to literature values. RESULTS A general agreement was seen between the estimated and literature dielectric properties of several liquids, particularly for high permittivity materials. The estimated and literature permittivity of distilled water is shown in Figure 1. Several biological tissues were then measured such as human calf and heel, and porcine bone excisions. Literature values for these properties are limited as they are often done using local probes which only measure the properties at the surface of a sample.DISCUSSION AND CONCLUSIONS A calibration method has been adapted to enable an ultra-wideband antenna system to assess dielectric properties of in vivo tissue at microwave frequencies. The estimated properties of the tested liquids align closely to literature, providing confidence in estimates of biological tissues which have limited literature values. This technique can be used towards microwave radar signal speed estimates, and for quantitative property measurements. Future improvements could include a skin subtraction method to isolate the properties of bone or other tissue under the skin, and development towards microwave bone health assessment

A PRINCIPLE INVESTIGATION INTO THE FEASIBILITY OF USING MICROWAVE IMAGING TO MONITOR BONE HEALTH

INTRODUCTION Assessing bone health is of particular interest in age-associated disease and traumas such as osteoporosis, and fractures from extreme sports. Having tools that can safely and accurately assess bone health allows for the screening, diagnosis, and monitoring of disease or injury. The current gold standard for assessing bone health is high-resolution peripheral quantitative computed tomography (HR-pQCT) allowing direct three-dimensional (3D) visualization of bone. Recent evidence suggests microwave imaging can be a complementary medical imaging tool to HR-pQCT for dynamic assessment of full bone health [1]. Specifically, it was shown that microwave properties of cancellous bone are sensitive to physical changes in bone. However, this study was purely exploratory and provided no direct evidence for changes in dielectric properties with varying bone health. In this study, we aim to understand the interaction of electromagnetic waves with bone as a composite material, specifically the material anisotropy. Such information would be crucial to understanding how microwave measurements relate to the physical characteristics of the bone. METHODS Image data for the right and left tibia and radius of one female and two male subjects was acquired from HR-pQCT (XtremeCTII, Scanco Medical). The 3D image data was smoothed with a Gaussian filter (σ = 1.6) and segmented using histogram based segmentation. Cubes of edge length 82 voxels (5.002 mm) were extracted from the segmented images based on the bone center of geometry. The extracted cubes were imported into electromagnetic simulation software (SEMCAD X, Schmid & Partner Engineering AG). A parallel plate waveguide filled with air was excited with a Gaussian pulse polarized in the z-axis (f0 = 6.5 GHz, BW = 11 GHz). The bone and marrow were assigned material properties from literature [2]. Resulting data was exported and processed using custom MATLAB scripts (R2013a, MathWorks). Three simulations were performed per image such that the electromagnetic wave was polarized in each of the three anatomical directions: anterior-posterior, medial-lateral, and proximal-distal. RESULTS The effective permittivity, ε’r, was calculated for each of the anatomical directions and plotted across the frequency range of the input signal. A representative plot for all images is shown in Figure 1. The effective permittivity for each orientation tend to vary around a common permittivity.DISCUSSION AND CONCLUSIONS The results presented here provide a rudimentary but novel insight into the anisotropic behaviour of bone at microwave frequencies. Furthermore, it presents a technique for 3D model acquisition and simulation of bone not yet present in literature. This technique will allow further exploration of the electromagnetic properties of bone such as a deeper insight into the anisotropic behaviour and development of a model for the effective medium of bone as a composite material. With such information, the microwave measurements of bone could be directly related to the bone’s physical properties. This would prove the potential of microwaves to assess bone health for disease or trauma and allow the development of in vivo imaging tools for assessing disease and trauma

Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response

Background: Most trials regarding catheter-based renal sympathetic denervation (RDN) describe a proportion of patients without blood pressure response. Recently, we were able to show arterial stiffness, measured by invasive pulse wave velocity (IPWV), seems to be an excellent predictor for blood pressure response. However, given the invasiveness, IPWV is less suitable as a selection criterion for patients undergoing RDN. Consequently, we aimed to investigate the value of cardiac magnetic resonance (CMR) based measures of arterial stiffness in predicting the outcome of RDN compared to IPWV as reference. Methods: Patients underwent CMR prior to RDN to assess ascending aortic distensibility (AAD), total arterial compliance (TAC), and systemic vascular resistance (SVR). In a second step, central aortic blood pressure was estimated from ascending aortic area change and flow sequences and used to re-calculate total arterial compliance (cTAC). Additionally, IPWV was acquired. Results: Thirty-two patients (24 responders and 8 non-responders) were available for analysis. AAD, TAC and cTAC were higher in responders, IPWV was higher in non-responders. SVR was not different between the groups. Patients with AAD, cTAC or TAC above median and IPWV below median had significantly better BP response. Receiver operating characteristic (ROC) curves predicting blood pressure response for IPWV, AAD, cTAC and TAC revealed areas under the curve of 0.849, 0.828, 0.776 and 0.753 (p = 0.004, 0.006, 0.021 and 0.035). Conclusions: Beyond IPWV, AAD, cTAC and TAC appear as useful outcome predictors for RDN in patients with hypertension. CMR-derived markers of arterial stiffness might serve as non-invasive selection criteria for RDN

A protocol for a randomised double-blind placebo-controlled feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing and remitting multiple sclerosis (RRMS)

Background: Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis. Methods: Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (< 10 years) of relapsing and remitting MS (RRMS) and who are over 18 years of age will be recruited from neurology clinics and throughout the Thames Valley community. During a 6-week nutrition intervention period, participants will consume the cocoa beverage, high flavonoid or low flavonoid content, at breakfast daily. At baseline, demographic factors and disease-related factors will be assessed. Fatigue, activity and quality of life, in addition to other measures, will be taken at three visits (baseline, week 3 and week 6) in a university setting by a researcher blinded to group membership. Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial.We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. Discussion: We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. Trial registration: Registered with ISRCTN Registry. Trial registration No: ISRCTN69897291; Date April 2016

Dynamic Allostery in the Methionine Repressor Revealed by Force Distribution Analysis

Many fundamental cellular processes such as gene expression are tightly regulated by protein allostery. Allosteric signal propagation from the regulatory to the active site requires long-range communication, the molecular mechanism of which remains a matter of debate. A classical example for long-range allostery is the activation of the methionine repressor MetJ, a transcription factor. Binding of its co-repressor SAM increases its affinity for DNA several-fold, but has no visible conformational effect on its DNA binding interface. Our molecular dynamics simulations indicate correlated domain motions within MetJ, and quenching of these dynamics upon SAM binding entropically favors DNA binding. From monitoring conformational fluctuations alone, it is not obvious how the presence of SAM is communicated through the largely rigid core of MetJ and how SAM thereby is able to regulate MetJ dynamics. We here directly monitored the propagation of internal forces through the MetJ structure, instead of relying on conformational changes as conventionally done. Our force distribution analysis successfully revealed the molecular network for strain propagation, which connects collective domain motions through the protein core. Parts of the network are directly affected by SAM binding, giving rise to the observed quenching of fluctuations. Our results are in good agreement with experimental data. The force distribution analysis suggests itself as a valuable tool to gain insight into the molecular function of a whole class of allosteric proteins

Flexibility of a biotinylated ligand in artificial metalloenzymes based on streptavidin—an insight from molecular dynamics simulations with classical and ab initio force fields

In the field of enzymatic catalysis, creating activity from a non catalytic scaffold is a daunting task. Introduction of a catalytically active moiety within a protein scaffold offers an attractive means for the creation of artificial metalloenzymes. With this goal in mind, introduction of a biotinylated d6-piano-stool complex within streptavidin (SAV) affords enantioselective artificial transfer-hydrogenases for the reduction of prochiral ketones. Based on an X-ray crystal structure of a highly selective hybrid catalyst, displaying significant disorder around the biotinylated catalyst [η6-(p-cymene)Ru(Biot-p-L)Cl], we report on molecular dynamics simulations to shed light on the protein–cofactor interactions and contacts. The results of these simulations with classical force field indicate that the SAV-biotin and SAV-catalyst complexes are more stable than ligand-free SAV. The point mutations introduced did not affect significantly the overall behavior of SAV and, unexpectedly, the P64G substitution did not provide additional flexibility to the protein scaffold. The metal-cofactor proved to be conformationally flexible, and the S112K or P64G mutants proved to enhance this effect in the most pronounced way. The network of intermolecular hydrogen bonds is efficient at stabilizing the position of biotin, but much less at fixing the conformation of an extended biotinylated ligand. This leads to a relative conformational freedom of the metal-cofactor, and a poorly localized catalytic metal moiety. MD calculations with ab initio potential function suggest that the hydrogen bonds alone are not sufficient factors for full stabilization of the biotin. The hydrophobic biotin-binding pocket (and generally protein scaffold) maintains the hydrogen bonds between biotin and protein

Utility of Atherosclerosis Imaging in the Evaluation of High-Density Lipoprotein–Raising Therapies

Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C–raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C–raising compounds are effective involve improvement of cholesterol uptake from macrophages in plaque for transport back to the liver, improvement of endothelial function, and anti-inflammatory effects. Vascular imaging can aid in the determination which HDL-C–raising compounds are effective. Ultrasound and MRI have proved suitable for assessment of structural changes of the vessel wall. Ultrasound can also be used or assessment of endothelial function. 18F-fluordeoxyglucose positron emission tomography has opened up the possibility to assess vessel wall inflammation. In this article we discuss these various imaging techniques and how they can assess efficacy as well as provide pathophysiologic information on the mechanism of action of novel HDL-C–raising drugs

Characterization of the thermal and photoinduced reactions of photochromic spiropyrans in aqueous solution

Six water-soluble spiropyran derivatives have been characterized with respect to the thermal and photoinduced reactions over a broad pH-interval. A comprehensive kinetic model was formulated including the spiro- and the merocyanine isomers, the respective protonated forms, and the hydrolysis products. The experimental studies on the hydrolysis reaction mechanism were supplemented by calculations using quantum mechanical (QM) models employing density functional theory. The results show that (1) the substitution pattern dramatically influences the pKa-values of the protonated forms as well as the rates of the thermal isomerization reactions, (2) water is the nucleophile in the hydrolysis reaction around neutral pH, (3) the phenolate oxygen of the merocyanine form plays a key role in the hydrolysis reaction. Hence, the nonprotonated merocyanine isomer is susceptible to hydrolysis, whereas the corresponding protonated form is stable toward hydrolytic degradation