Monosynaptic connections between pairs of spiny stellate cells in layer 4 and pyramidal cells in layer 5A indicate that lemniscal and paralemniscal afferent pathways converge in the infragranular somatosensory cortex.

Monosynaptic interlaminar connections between spiny stellate cells in layer 4 (L4), the main cortical recipient layer for thalamic projections, and pyramidal cells in layer 5A (L5A), one of the main cortical output layers, were examined anatomically and functionally by paired recordings in acute brain slices. The somata of pairs forming interlaminar L4-to-L5A connections were located predominantly close to or directly under the barrel-septum wall in layer 4. Superposition of spiny stellate axon arbors and L5A pyramidal cell dendritic arbors suggested an innervation domain underneath an L4 barrel wall. Functionally, the L4-to-L5A connections were of high reliability and relatively low efficacy, with a unitary EPSP amplitude of 0.6 mV, and the connectivity was moderately high (one in seven pairs tested was connected). The EPSP amplitude was weakly depressing (paired-pulse ratio of approximately 0.8) during repetitive presynaptic action potentials at 10 Hz. The existence of Monosynaptic L4-to-L5A connections indicates that the specific 'lemniscal' thalamic input from the ventro-basal nucleus of the thalamus to the cortex and the more unspecific 'paralemniscal' afferent thalamic projections from the posterior medial nucleus of the thalamus merge already at an initial stage of cortical signal processing. These Monosynaptic connections establish a Monosynaptic coupling of the input to the cortex and its output, thereby effectively bypassing the supragranular layers

Late-Onset Multiple Self-Healing Squamous Epithelioma Ferguson-Smith Recurrence Induced by Radiotherapy.

We report the case of a woman in her 60s with confirmed multiple self-healing squamous epitheliomas (MSSE) Ferguson-Smith. After recurrences following surgery and radiotherapy, the patient was successfully treated with minimal surgical intervention combined with intralesional injections of triamcinolone acetate. The histological comparison between mature and regressed keratoacanthomas (KA) revealed an increased inflammatory infiltrate with numerous plasmacytoid dendritic cells in the regressed KA in comparison to the mature one, speaking in favor of an inflammation-mediated regression process. Corticosteroids injection in MSSE may have paradoxical effects with action on the proliferation phase rather than the inflammatory regression phase of the KA. Our case confirms previous reports showing that radiotherapy may exacerbate MSSE and should be avoided. Intralesional triamcinolone acetate injection is a safe and easy to use method also effective for multiple lesions. Our case underlines the difference between squamous cell carcinoma and KA, responding differently to therapies like imiquimod or radiotherapy

Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP

Image Perceptual Similarity Metrics for the Assessment of Basal Cell Carcinoma.

Efficient management of basal cell carcinomas (BCC) requires reliable assessments of both tumors and post-treatment scars. We aimed to estimate image similarity metrics that account for BCC's perceptual color and texture deviation from perilesional skin. In total, 176 clinical photographs of BCC were assessed by six physicians using a visual deviation scale. Internal consistency and inter-rater agreement were estimated using Cronbach's α, weighted Gwet's AC2, and quadratic Cohen's kappa. The mean visual scores were used to validate a range of similarity metrics employing different color spaces, distances, and image embeddings from a pre-trained VGG16 neural network. The calculated similarities were transformed into discrete values using ordinal logistic regression models. The Bray-Curtis distance in the YIQ color model and rectified embeddings from the 'fc6' layer minimized the mean squared error and demonstrated strong performance in representing perceptual similarities. Box plot analysis and the Wilcoxon rank-sum test were used to visualize and compare the levels of agreement, conducted on a random validation round between the two groups: 'Human-System' and 'Human-Human.' The proposed metrics were comparable in terms of internal consistency and agreement with human raters. The findings suggest that the proposed metrics offer a robust and cost-effective approach to monitoring BCC treatment outcomes in clinical settings

An Annotated Draft Genome for Radix auricularia (Gastropoda, Mollusca)

Molluscs are the second most species-rich phylum in the animal kingdom, yet only 11 genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72×. The assembly contains 94.6% of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ∼690 Mb compared with the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70% mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Global vulnerability hotspots: differences and agreement between international indicator-based assessments

Climate change impacts and their consequences are determined not only by the intensity and frequency of different climatic hazards but also by the vulnerability of the system, society or community exposed. While general agreement exists about the importance of assessing vulnerability to understand climate risks, there is still a tendency to neglect global and regional vulnerability patterns because they are hard to quantify, despite their value in informing adaptation, disaster risk and development policies. Several approaches to quantifying global vulnerability exist. These differ in terms of the indicators they use and how they classify countries or regions into vulnerability classes. The paper presents the structure of selected approaches and explores two indices in depth. The aim of this paper is to assess the level of agreement between selected international indicator-based assessments of vulnerability, at the level of climate regions. Results suggest that the two major global vulnerability assessments analysed largely agree on the location of the most and least vulnerable regions when these assessments are aggregated to a regional scale using the IPCC’s climate regions. The paper then discusses the robustness of the information derived and its usefulness for adaptation, disaster risk and development policies. Measuring progress towards reducing vulnerability to climate change and hazards is key for various agencies and actors in order to be able to develop informed policies and strategies for managing climate risks and to promote enabling conditions for achieving the SDGs and building resilience

Towards a Mathematical Theory of Cortical Micro-circuits

The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM), can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model