Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalinfixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (\u3c45 \u3eyears). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Analysis and assessment of energy efficiency of passenger lifts

The energy performance and operational characteristics of the passenger lift investigated in this study were based on energy consumption data registered throughout the normal duty cycle. An overview is provided of available methods employed to evaluate the energy uptake of passenger lifts, relying mostly on energy consumption measurements taken on a real object over an idealised reference duty cycle. Measurement data were used to determine the energy efficiency rating of the lift during the trip cycle and in the standby mode and the energy demand levels, which are then to be compared with measurement results obtained under the service conditions

Optimisation of the Magnetic Circuit of a Measuring Head for Diagnostics of Steel-Polyurethane Load-Carrying Belts Using Numerical Methods

The paper describes the process of a prototype head optimisation for magnetic diagnostics of steel-polyurethane load-carrying belts. The prototype, validated on a number of cranes, was subject to an improvement and optimisation attempt using numerical analysis of magnetic field distribution in the magnetic circuit, tested load-carrying belt, and environment. The analysis was carried out in the ANSYS environment using PDS—Probabilistic Design System tools (DOE—Design of Experiment). Taking the dimensions of individual elements of the magnetic circuit, material densities, and magnetic material properties as the input data, the magnetic circuit was optimised with respect to metrological properties as well as mass and size criteria. Based on the analyses carried out and the results obtained, the head design was modernised, which involved changing the geometry of elements forming the magnetic circuit. Based on observations made during tests of the prototype version of the device performed on real objects, several improvements were also proposed, consisting of the replacement of selected components with elements printed in the FDM technology. The correctness of the performed numerical analyses was verified by comparing the measured and calculated values of the total magnetic field induction in the defined plane of the magnetic circuit. The prototype versions of heads before and after modernisation were subject to comparative tests. Under laboratory conditions, both versions of heads were used to diagnose the steel-polyurethane load-carrying belts with modelled damages. The obtained test results and their statistical characteristics were analysed in detail

CFD Simulations of the New Construction of Light Brattice Wall for Mine Shafts

Brattice walls in mine shafts are used for various purposes, for example, permanent brattice walls can be used to separate ventilation sections. They can be also used in the case of modernization of the hoisting system, as it is in Shaft no. 1 of the Szczygłowice department, part of the Knurów-Szczyłowice coal mine. To shorten the time and reduce costs of the hoist modernization, the shaft is to be partitioned into two sections—with the hoist operating in one of them and another one being modernized in the other section. The new construction of the light brattice wall was designed for this purpose. To prove its usefulness and safety it was tested in the laboratory and computer simulations. The following paper presents CFD simulations of the brattice—its methodology and results together with an overview of works to be conducted in the shaft