Hidradenitis suppurativa: Detangling phenotypes and identifying common denominators.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a severe impact on patients' quality of life through its recurrent and painful nature, as well as its comorbidity burden. The shift in the pathogenic paradigm from a condition of the apocrine glands to an autoinflammatory disease associated with follicular destruction has rendered its understanding difficult, as there are still large gaps in pinpointing the underlying mechanisms, which cannot currently explain the existing clinical variation and as a result, translate into suboptimal therapy. Multifactorial involvement is hypothesized, with an implication of genetic mutations, microbiome dysbiosis, cytokine upregulation and environmental factors. Clinical observation is fundamental for diagnosis, however, the marked heterogeneity in presentation leads to delays in detection and challenges in treatment selection, showcasing clear limits in defining the link between genetic aspects of HS, the role of epigenetic factors and its pathogenic pathways. There have been attempts to formulate phenotypes that could aid in prognostication and management, however, current classification schemata show significant overlap and no validation through longitudinal studies. In this context, nomenclature poses a great challenge due to the lack of global agreement in the definition of lesions, which should be addressed by future research to enable simplified recognition and allow for more precise severity scoring. This could be complemented by the addition of extra dermatologic findings or paraclinical assessment in constructing phenotypes. The development of valid, predictive and reliable classifications of HS may lead to an improvement in comprehending its pathophysiology, favouring a more personalized approach in management. This could be achieved through consensus in the characterization of clinical features and data gathering, as well as validation attempts for described phenotypes. Ultimately, the genotype-endotype-phenotype correlation in HS requires targeted, systematic inquiries and should be addressed more largely to broaden the perspective on this debilitating entity.

Role of Cannabinoids in Oral Cancer.

Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds. Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy. Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.

Intersecting Pathways: Nonalcoholic Fatty Liver Disease and Psoriasis Duet-A Comprehensive Review.

Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients' quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The "hepato-dermal axis" is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.

Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.

Control Architecture for Connected Vehicle Platoons: From Sensor Data to Controller Design Using Vehicle-to-Everything Communication.

A suitable control architecture for connected vehicle platoons may be seen as a promising solution for today's traffic problems, by improving road safety and traffic flow, reducing emissions and fuel consumption, and increasing driver comfort. This paper provides a comprehensive overview concerning the defining levels of a general control architecture for connected vehicle platoons, intending to illustrate the options available in terms of sensor technologies, in-vehicle networks, vehicular communication, and control solutions. Moreover, starting from the proposed control architecture, a solution that implements a Cooperative Adaptive Cruise Control (CACC) functionality for a vehicle platoon is designed. Also, two control algorithms based on the distributed model-based predictive control (DMPC) strategy and the feedback gain matrix method for the control level of the CACC functionality are proposed. The designed architecture was tested in a simulation scenario, and the obtained results show the control performances achieved using the proposed solutions suitable for the longitudinal dynamics of vehicle platoons.

Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis.

The skin is a complex organ that includes a wide variety of tissue types with different embryological origins [...].

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts.

Early diagnosis is essential for completely eradicating skin cancer and maximizing patients' clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), optical coherence tomography (OCT), magnetic resonance imaging (MRI), near-infrared (NIR) bioimaging, positron emission tomography (PET), and their combinations provide non-invasive imaging data that may help in the early detection of cutaneous tumors and surgical planning. Hence, they seem appropriate for observing dynamic processes such as blood flow, immune cell activation, and tumor energy metabolism, which may be relevant for disease evolution. This review discusses the latest technological and methodological advances in imaging techniques that may be applied for skin cancer detection and monitoring. In the first instance, we will describe the principle and prospective clinical applications of the most commonly used imaging techniques, highlighting the challenges and opportunities of their implementation in the clinical setting. We will also highlight how imaging techniques may complement the molecular and histological approaches in sharpening the non-invasive skin characterization, laying the ground for more personalized approaches in skin cancer patients.

Kaempferol: A Review of Current Evidence of Its Antiviral Potential.

Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as hepatitis B virus, viruses of the alphaherpesvirinae family, African swine fever virus, and pseudorabies virus; they were also effective against RNA viruses, namely feline SARS coronavirus, dengue fever virus, Japanese encephalitis virus, influenza virus, enterovirus 71, poliovirus, respiratory syncytial virus, human immunodeficiency virus, calicivirus, and chikungunya virus. On the other hand, no effectiveness against murine norovirus and hepatitis A virus could be determined. The antiviral action mechanisms of kaempferol compounds are various, such as the inhibition of viral polymerases and of viral attachment and entry into host cells. Future research should be focused on further elucidating the antiviral properties of kaempferol compounds from different plants and assessing their potential use to complement the action of antiviral drugs.

Coalitional Distributed Model Predictive Control Strategy for Vehicle Platooning Applications.

This work aims at developing and testing a novel Coalitional Distributed Model Predictive Control (C-DMPC) strategy suitable for vehicle platooning applications. The stability of the algorithm is ensured via the terminal constraint region formulation, with robust positively invariant sets. To ensure a greater flexibility, in the initialization part of the method, an invariant table set is created containing several invariant sets computed for different constraints values. The algorithm was tested in simulation, using both homogeneous and heterogeneous initial conditions for a platoon with four homogeneous vehicles, using a predecessor-following, uni-directionally communication topology. The simulation results show that the coalitions between vehicles are formed in the beginning of the experiment, when the local feasibility of each vehicle is lost. These findings successfully prove the usefulness of the proposed coalitional DMPC method in a vehicle platooning application, and illustrate the robustness of the algorithm, when tested in different initial conditions.

Shaking Table Attached to Magnetorheological Damper: Simulation and Experiments for Structural Engineering.

This paper details how to construct a small-scale shaking table attached to a magnetorheological (MR) damper. The motivation for this construction relies on the increasing interest in modeling the dynamics of MR dampers-MR dampers have been used in structures for safety reasons. To model the MR damper, we use the so-called 'Dahl model', which is useful to represent systems with a hysteresis. The Dahl model, validated through experimental data collected in a laboratory, was combined with a linear model to represent a two-story building. This two-story building model allows us to simulate the dynamics of that building when its floors are attached to MR dampers. By doing so, we can assess-through simulation-to what extent MR dampers can protect structures from vibrations. Using data from the 'El Centro' earthquake (1940), we can conclude that MR dampers have the potential to reduce the impact of earthquakes upon structures. This finding emphasizes the potential benefits of MR dampers for the safety of structures, which is a conclusion taken from the apparatus detailed in this paper.

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism's response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.

Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications.

Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.

Reply to Çinar et al. Comment on "Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874".

We would like to thank Çinar et al. for their appreciation and insightful discussions presented in their comment [...].

Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases.

BACKGROUND: During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine. METHODS AND RESULTS: Case 1: A female patient was admitted with a suspicious cervical mass that emerged within one week after the administration of second dose of the BNT162b2 COVID-19 vaccine. Surgical removal followed by pathology assessment of the specimen confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Case 2: A male patient was admitted with multiple ulcerative oral lesions arising on the third day after the initial dose of the BNT162b2 COVID-19 vaccine. These lesions had a progressive character and during the following months were complicated with repetitive episodes of heavy oral bleeding, requiring blood transfusions. The incisional biopsy of the lesions and pathological assessment of the specimens confirmed the diagnosis of T/NK-cell lymphoma. CONCLUSIONS: The safety profile of the mRNA-based vaccines is an undeniable fact. In most cases, suspicions of potentially aggressive side effects were ruled out, proving to be transient post-vaccine reactions. Clinicians should remain alert to report any potentially aggressive manifestations emerging in the context of mRNA COVID-19 vaccination, such as these cases of hematological malignancies, in order to promote additional investigations on the particular mechanisms of action of COVID-19 vaccines and to provide the best medical care to the patients.

Complex Interaction Among Immune, Inflammatory, and Carcinogenic Mechanisms in the Head and Neck Squamous Cell Carcinoma.

Inflammation is deeply involved in the development of most types of cancer. Many studies focus on the interaction between immune-inflammatory mechanisms and tumorigenesis in the head and neck squamous cell carcinoma (HNSCC). In this chapter, we emphasize the complexity of processes underlying this interaction and discuss the mechanisms of carcinogenesis in HNSCC with a special focus on metabolic changes, inflammation, and the immune landscape. Unveiling complex connections between immuno-inflammatory processes and tumor initiation, promotion, and progression will open new directions in the reliable identification of predictive factors and therapeutic targets in HNSCC.

A Coalitional Distributed Model Predictive Control Perspective for a Cyber-Physical Multi-Agent Application.

Following the current technological development and informational advancement, more and more physical systems have become interconnected and linked via communication networks. The objective of this work is the development of a Coalitional Distributed Model Predictive Control (C- DMPC) strategy suitable for controlling cyber-physical, multi-agent systems. The motivation behind this endeavour is to design a novel algorithm with a flexible control architecture by combining the advantages of classical DMPC with Coalitional MPC. The simulation results were achieved using a test scenario composed of four dynamically coupled sub-systems, connected through an unidirectional communication topology. The obtained results illustrate that, when the feasibility of the local optimization problem is lost, forming a coalition between neighbouring agents solves this shortcoming and maintains the functionality of the entire system. These findings successfully prove the efficiency and performance of the proposed coalitional DMPC method.

Multivariable Optimisation for Waiting-Time Minimisation at Roundabout Intersections in a Cyber-Physical Framework.

The evolution of communication networks offers new possibilities for development in the automotive industry. Smart vehicles will benefit from the possibility of connecting with the infrastructure and from an extensive exchange of data between them. Furthermore, new control strategies can be developed that benefit the advantages of these communication networks. In this endeavour, the main purposes considered by the automotive industry and researchers from academia are defined by: (i) ensuring people's safety; (ii) reducing the overall costs, and (iii) improving the traffic by maximising the fluidity. In this paper, a cyber-physical framework (CPF) to control the access of vehicles in roundabout intersections composed of two levels is proposed. Both levels correspond to the cyber part of the CPF, while the physical part is composed of the vehicles crossing the roundabout. The first level, i.e., the edge-computing layer, is based on an analytical solution that uses multivariable optimisation to minimise the waiting times of the vehicles entering a roundabout intersection and to ensure a safe crossing. The second level, i.e., the cloud-computing layer, stores information about the waiting times and trajectories of all the vehicles that cross the roundabout and uses them for long-term analysis and prediction. The simulated results show the efficacy of the proposed method, which can be easily implemented on an embedded device for real-time operation.

Adaptive SNN for Anthropomorphic Finger Control.

Anthropomorphic hands that mimic the smoothness of human hand motions should be controlled by artificial units of high biological plausibility. Adaptability is among the characteristics of such control units, which provides the anthropomorphic hand with the ability to learn motions. This paper presents a simple structure of an adaptive spiking neural network implemented in analogue hardware that can be trained using Hebbian learning mechanisms to rotate the metacarpophalangeal joint of a robotic finger towards targeted angle intervals. Being bioinspired, the spiking neural network drives actuators made of shape memory alloy and receives feedback from neuromorphic sensors that convert the joint rotation angle and compression force into the spiking frequency. The adaptive SNN activates independent neural paths that correspond to angle intervals and learns in which of these intervals the rotation the finger rotation is stopped by an external force. Learning occurs when angle-specific neural paths are stimulated concurrently with the supraliminar stimulus that activates all the neurons that inhibit the SNN output stopping the finger. The results showed that after learning, the finger stopped in the angle interval in which the angle-specific neural path was active, without the activation of the supraliminar stimulus. The proposed concept can be used to implement control units for anthropomorphic robots that are able to learn motions unsupervised, based on principles of high biological plausibility.

Tumour Microenvironment in Skin Carcinogenesis.

Tumour microenvironment is a complex system comprising cells and molecules that will provide the necessary conditions for tumour development and progression. Cells residing in the tumour microenvironment gain specific phenotypes and specific functions that are pro-tumorigenic. Tumour progression is in fact a combination between tumour cell characteristics and its interplay with tumour microenvironment. This dynamic network will allow tumour cells to grow, migrate and invade tissues. In the present chapter, we are highlighting some traits that characterise tumour microenvironment in basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma. In skin cancers, there are some common tumour microenvironment characteristics such as the presence of tumour-associated macrophages and regulatory T lymphocytes that are non-tumour cells promoting tumorigenesis. There are also skin cancer type differences in terms of tumour microenvironment characteristics. Thus, markers such as macrophage migration inhibitory factor in melanoma or the extraordinary diverse genetic make-up in the cancer-associated fibroblasts associated to squamous cell carcinoma are just a few of specific traits in skin cancer types. New technological advances for evaluation of tumour environment are presented. Thus, non-invasive skin imaging techniques such as reflectance confocal microscopy can evaluate skin tumour inflammatory infiltrates for density and cellular populations. Analysing tumour micromedium in depth may offer new insights into cancer therapy and identify new therapy targets.

The Effects of Capsaicin on Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients' survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.