Non-invasive scoring of cellular atypia in keratinocyte cancers in 3D LC-OCT images using Deep Learning

Diagnosis based on histopathology for skin cancer detection is today's gold standard and relies on the presence or absence of biomarkers and cellular atypia. However it suffers drawbacks: it requires a strong expertise and is time-consuming. Moreover the notion of atypia or dysplasia of the visible cells used for diagnosis is very subjective, with poor inter-rater agreement reported in the literature. Lastly, histology requires a biopsy which is an invasive procedure and only captures a small sample of the lesion, which is insufficient in the context of large fields of cancerization. Here we demonstrate that the notion of cellular atypia can be objectively defined and quantified with a non-invasive in-vivo approach in three dimensions (3D). A Deep Learning (DL) algorithm is trained to segment keratinocyte (KC) nuclei from Line-field Confocal Optical Coherence Tomography (LC-OCT) 3D images. Based on these segmentations, a series of quantitative, reproducible and biologically relevant metrics is derived to describe KC nuclei individually. We show that, using those metrics, simple and more complex definitions of atypia can be derived to discriminate between healthy and pathological skins, achieving Area Under the ROC Curve (AUC) scores superior than 0.965, largely outperforming medical experts on the same task with an AUC of 0.766. All together, our approach and findings open the door to a precise quantitative monitoring of skin lesions and treatments, offering a promising non-invasive tool for clinical studies to demonstrate the effects of a treatment and for clinicians to assess the severity of a lesion and follow the evolution of pre-cancerous lesions over time.© 2022. The Author(s)

Dynamics of positive- and negative-mass solitons in optical lattices and inverted traps

We study the dynamics of one-dimensional solitons in the attractive and repulsive Bose-Einstein condensates (BECs) loaded into an optical lattice (OL), which is combined with an external parabolic potential. First, we demonstrate analytically that, in the repulsive BEC, where the soliton is of the gap type, its effective mass is \emph{negative}. This gives rise to a prediction for the experiment: such a soliton cannot be not held by the usual parabolic trap, but it can be captured (performing harmonic oscillations) by an anti-trapping inverted parabolic potential. We also study the motion of the soliton a in long system, concluding that, in the cases of both the positive and negative mass, it moves freely, provided that its amplitude is below a certain critical value; above it, the soliton's velocity decreases due to the interaction with the OL. At a late stage, the damped motion becomes chaotic. We also investigate the evolution of a two-soliton pulse in the attractive model. The pulse generates a persistent breather, if its amplitude is not too large; otherwise, fusion into a single fundamental soliton takes place. Collisions between two solitons captured in the parabolic trap or anti-trap are considered too. Depending on their amplitudes and phase difference, the solitons either perform stable oscillations, colliding indefinitely many times, or merge into a single soliton. Effects reported in this work for BECs can also be formulated for optical solitons in nonlinear photonic crystals. In particular, the capture of the negative-mass soliton in the anti-trap implies that a bright optical soliton in a self-defocusing medium with a periodic structure of the refractive index may be stable in an anti-waveguide.Comment: 22pages, 9 figures, submitted to Journal of Physics

Estimating Dengue Transmission Intensity from Case-Notification Data from Multiple Countries

Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions.We estimated the force of infection (λ) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age-stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under-reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries.As expected, estimates varied widely across and within countries, highlighting the spatio-temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age-stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available

Ex Vivo Confocal Microscopy Using Fusion Mode and Digital Staining: Changing Paradigms in Histological Diagnosis

La microscopia confocal ex vivo es un sistema de procesamiento de tejidos que permite el análisis histológico inmediato de tejidos extirpados por medio de láseres diodo con distintos espectros de longitud de onda. En estudios previos la microscopia confocal ex vivo reduce el tiempo de análisis de márgenes de forma muy notable, con una sensibilidad y especificidad respecto a la histopatología del 88% y 99%, respectivamente. Recientemente se ha desarrollado una nueva tecnología que es capaz de proveer imágenes digitales con mayor velocidad y mejor resolución que las obtenidas en los dispositivos previos. Mediante el método de fusión (láseres de fluorescencia y reflectancia que escanean simultáneamente), se reproduce con una tinción digital la hematoxilina y eosina de forma inmediata en cada imagen. La implementación de esta nueva tecnología ha abierto definitivamente una puerta en el diagnóstico inmediato de tejidos.The ex vivo confocal microscope is an imaging system designed to analyze freshly excised tissue using two diode lasers with different wavelengths. The technique can dramatically reduce margin analysis times and offers a sensitivity of 88% and a specificity of 89% relative to histopathology. A new technology has recently been developed that produces images more quickly and with a higher resolution than before. By means of a fusion mode that combines simultaneously scanned fluorescence and reflectance images, it produces digitally stained images that simulate the effect of hematoxylin-eosin staining. Application of this new technology has opened the door to real-time tissue diagnostics

Consenso de terminología en microscopia confocal de reflectancia en español mediante método Delphi

Resumen: La terminología usada para describir los diferentes hallazgos en la microscopía confocal de reflectancia (MCR), tanto en lesiones melanocíticas, como en no melanocíticas se ha consensuado en inglés. En el presente trabajo, se proponen los términos en español que mejor interpretan estos conceptos ya descritos para la MCR, mediante el consenso de expertos de distintas nacionalidades de habla hispana y utilizando el método DELPHI para el acuerdo final. Se obtuvieron 52 términos en total, de los cuales 28 fueron para lesiones melanocíticas y 24 para lesiones no melanocíticas. El uso de la nomenclatura propuesta permitirá una homogeneización y mejor entendimiento de las estructuras; una descripción más estandarizada en los registros clínicos y una mejor interpretación de estos informes por otros dermatólogos. Abstract: The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists

[Translated article] Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists. Resumen: La terminología usada para describir los diferentes hallazgos en la microscopía confocal de reflectancia (MCR), tanto en lesiones melanocíticas, como en no melanocíticas se ha consensuado en inglés. En el presente trabajo, se proponen los términos en español que mejor interpretan estos conceptos ya descritos para la MCR, mediante el consenso de expertos de distintas nacionalidades de habla hispana y utilizando el método DELPHI para el acuerdo final. Se obtuvieron 52 términos en total, de los cuales 28 fueron para lesiones melanocíticas y 24 para lesiones no melanocíticas. El uso de la nomenclatura propuesta permitirá una homogeneización y mejor entendimiento de las estructuras; una descripción más estandarizada en los registros clínicos y una mejor interpretación de estos informes por otros dermatólogos

Are diuretics overused in the treatment of chronic heart failure?

Diuretics are used for symptomatic treatment of chronic heart failure; however, no randomized trials have yet assessed the long-term effects of these agents on morbidity and mortality. In this article, Vaz Pérez and colleagues question the assumption that long-term diuretic therapy is beneficial and opine that the currently available data do not support the routine use of diuretics as a cornerstone of long-term medical treatment for patients with chronic heart failure