The evolution of protein-coding genes has both structural and regulatory components. The first can be assessed by measuring the ratio of non-synonymous to synonymous nucleotide substitutions. The second component can be measured as the normalized proportion of transposable elements that are used as regulatory elements. For the first time, we characterized in parallel the regulatory and structural evolutionary profiles for 10,890 human genes and 2972 molecular pathways. We observed a ~0.1 correlation between the structural and regulatory metrics at the gene level, which appeared much higher (~0.4) at the pathway level. We deposited the data in the publicly available database RetroSpect. We also analyzed the evolutionary dynamics of six cancer pathways of two major axes: Notch/WNT/Hedgehog and AKT/mTOR/EGFR. The Hedgehog pathway had both components slower, whereas the Akt pathway had clearly accelerated structural evolution. In particular, the major hub nodes Akt and beta-catenin showed both components strongly decreased, whereas two major regulators of Akt TCL1 and CTMP had outstandingly high evolutionary rates. We also noticed structural conservation of serine/threonine kinases and the genes related to guanosine metabolism in cancer signaling: GPCRs, G proteins, and small regulatory GTPases (Src, Rac, Ras); however, this was compensated by the accelerated regulatory evolution.

Implementing line-of-sight (LOS) and none-line-of-sight (NLOS) identification in ultra-wideband (UWB) systems is crucial. Convolutional neural network (CNN) based identification methods can extract higher-level features automatically, but they are based on channel impulse response (CIR)-turned image ingested features that impose calculation complexity and do not make use of manual features due to the data inundation risk. In this letter, we propose a novel multilayer perceptron (MLP)-based LOS/NLOS identification algorithm that can utilize both manually extracted features and feature from CNN based on raw CIR inputs with only 7.39% calculation complexity as compared to the traditional image-based CNN. Three experiments, at a teaching building, an office, and an underground mine, were conducted to verify the proposed method’s performance. Our proposed features are conducive to LOS/NLOS identification, especially the proposed raw CIR-based feature from the CNN, achieving 26.9% improvement over existing manual features. Furthermore, the proposed method outperformed the traditional image-based CNN with an improvement of 44.16%.

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much CDK2AP1 mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1–3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity.

Background: To assess readiness to achieve the WHO Global Strategy targets for HPV vaccination and cervical screening and to guide capacity building, the current status of these services in 18 Eastern European and Central Asian countries, territories and entities (CTEs) was evaluated. Methods: In order to assess the current status of HPV vaccination and cervical cancer screening in these 18 CTEs, a 30 question survey tool was developed, covering: national policies, strategies and plans for cervical cancer prevention; status of cancer registration; status of HPV vaccination; and current practices for cervical cancer screening and treatment of precancerous lesions. As cervical cancer prevention comes within the mandate of the United Nations Fund for Population Development (UNFPA), the UNFPA offices in the 18 CTEs have regular contact with national experts who are directly involved in cervical cancer prevention actions and are well placed to provide the data required for this survey. Working through the UNFPA offices, the questionnaires were sent to these national experts in April 2021, with data collected from April to July 2021. All CTEs returned completed questionnaires. Results: Only Armenia, Georgia, Moldova, North Macedonia, Turkmenistan and Uzbekistan have implemented national HPV vaccination programmes, with only the last 2 of these reaching the WHO target of 90% of girls fully vaccinated by age 15, while rates in the other 4 range from 8%-40%. Cervical screening is available in all CTEs but only Belarus and Turkmenistan have reached the WHO target of 70% of women screened once by age 35 and again by age 45, while rates elsewhere range from 2%-66%. Only Albania and Turkey follow the WHO recommendation to use a high-performance screening test, while the majority use cervical cytology as the main screening test and Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan use visual inspection. No CTEs currently operate systems to coordinate, monitor and quality assure (QA) the entire cervical screening process. Conclusions: Cervical cancer prevention services in this region are very limited. Achieving the WHO Global Strategy targets by 2030 will require substantial investments in capacity building by international development organisations.

Surgical site infections (SSIs) are the most common adverse event occurring in surgical patients. Optimal prevention of SSIs requires the bundled integration of a variety of measures before, during, and after surgery. Surgical antibiotic prophylaxis (SAP) is an effective measure for preventing SSIs. It aims to counteract the inevitable introduction of bacteria that colonize skin or mucosa into the surgical site during the intervention. This document aims to guide surgeons in appropriate administration of SAP by addressing six key questions. The expert panel identifies a list of principles in response to these questions that every surgeon around the world should always respect in administering SAP.

The main objective of this review was to investigate whether educational attainment has an impact on the occurrence of atrial fibrillation (AF) as well as the implementation of smart technology to detect this condition. Data on the relationship between education level and the occurrence of AF were collected, as well as data on smart devices for detecting AF. A lower level of education has been linked to an increased risk of AF. With this in mind, it is easy to explain the clear correlation between education level and AF, as well as the adoption of smart device detection and how it may improve illness prognosis. People with a higher level of education understand and embrace the notion of employing smart devices to detect and prevent AF; they also have decreased AF prevalence compared with those with a lower level of education.

(1) Background: Viral hepatitis C (HCV) and viral hepatitis B (HBV) are common co-infections in people living with HIV (PLWH). All PLWH should be vaccinated against HBV and hepatitis A (HAV) and treated for HBV and HCV. We aimed to compare testing, prophylaxis and treatment of viral hepatitis in PLWH in Central and Eastern Europe (CEE) in 2019 and 2022. (2) Methods: Data was collected through two on-line surveys conducted in 2019 and 2022 among 18 countries of the Euroguidelines in CEE (ECEE) Network Group. (3) Results: In all 18 countries the standard of care was to screen all PLWH for HBV and HCV both years; screening of HAV was routine in 2019 in 54.5% and in 2022 47.4% of clinics. Vaccination of PLWH against HAV was available in 2019 in 16.7%, in 2022 in 22.2% countries. Vaccination against HBV was available routinely and free of charge in 50% of clinics both in 2019 and 2022. In HIV/HBV co-infected the choice of NRTI was tenofovir-based in 94.4% of countries in both years. All clinics that responded had access to direct-acting antivirals (DAAs) but 50% still had limitations for treatment. (4) Conclusions: Although testing for HBV and HCV was good, testing for HAV is insufficient. Vaccination against HBV and especially against HAV has room for improvement; furthermore, HCV treatment access needs to overcome restrictions.

(1) Background: This study evaluates the effect of a conventional/low-voltage light-curing protocol (LV protocol) (10 s with 1340 mW/cm2) and high-voltage light-curing protocol (HV protocol) (3 s with 3440 mW/cm2) on the microhardness (MH) of dental resin-based composites (RBCs). Five resin composites were tested: conventional Evetric (EVT), Tetric Prime (TP), Tetric Evo Flow (TEF), bulk-fill Tetric Power Fill (PFL), and Tetric Power Flow (PFW). (2) Materials and Methods: Two tested composites (PFW and PFL) were designed for high-intensity light curing. The samples were made in the laboratory in specially designed cylindrical molds; diameter = 6 mm and height = 2 or 4 mm, depending on the type of composite. Initial MH was measured on the top and bottom surfaces of composite specimens 24 h after light curing using a digital microhardness tester (QNESS 60 M EVO, ATM Qness GmbH, Mammelzen, Germany). The correlation between the filler content (wt%, vol%) and the MH of the RBCs was tested. For the calculation of depth-dependent curing effectiveness, the bottom/top ratio for initial MH was used. (3) Conclusions: MH of RBCs is more dependent on material composition than on light-curing protocol. Filler wt% has a greater influence on MH values compared to filler vol%. The bottom/top ratio showed values over 80% for bulk composites, while for conventional sculptable composites, borderline or suboptimal values were measured for both curing protocols.

Nearby lightning strokes are often considered as a prime source of transient overvoltages in the substations. Lightning overvoltages can cause unreliable operation of power system and power supply interruptions. Calculation of expected lightning overvoltages is necessary to design appropriate protection system. This paper presents the analysis of the lightning overvoltage performance of real 400 kV overhead transmission line and gas insulated substation (GIS), considering various factors, such as lightning stroke locations, peak currents, front rise times, etc. EMTP-RV software was used to model transmission line and substation elements and conduct simulations, while transmission line lightning performance was determined using Sigma Slp software. The expected overvoltages and surge arrester currents are calculated and used to design lightning protection system of the considered substation. Obtained results also indicate the importance of proper modelling of power system elements and lightning strokes.

INTRODUCTION Sodium-glucose cotransporter-2 (SGLT2) inhibitors are integral in treating patients with heart failure, regardless of the existence of diabetes mellitus. In light of their benefits on the heart muscle, the question of their effect on acute coronary syndrome is raised, and a hypothesis as to whether they can be implemented in its treatment is proposed. The aim of the article was to indicate the potential of using SGLT2 inhibitors in the treatment of myocardial infarction (MI). EVIDENCE ACQUISITION A PubMed search for articles published between October 2017 and May 2022 was conducted using the following keywords: "SGLT2 inhibitors," "Acute Coronary Syndrome," "Treatment," "Prognosis." Reference lists of identified articles were searched for further articles. EVIDENCE SYNTHESIS Reports from clinical trials and animal studies thus far investigating mechanistic pathways of SGLT2 inhibitors' effect in relation to acute myocardial infarction were interplayed to extract relevant findings and analyze the safety of this therapy in acute coronary syndrome (ACS) patients. CONCLUSIONS SGLT2 inhibitors indicate beneficial effects in acute cardiovascular incident by various mechanisms, and early initiation of therapy may improve outcomes for AMI survivors.

Introduction The World Health Organization (WHO) Surgical Safety Checklist is a tool developed by the WHO to promote safer surgical practices and reduce the incidence of surgical errors and complications. This study aims to describe the role of assistant nurses in the implementation of this checklist by surgical teams. Materials and methods This descriptive study utilized a questionnaire-based survey conducted between September 2018 and March 2019 among 196 healthcare professionals at two surgical units in a university hospital in Sweden. The questionnaire covered demographic information such as age, gender, and occupation, as well as details about their workplace, experience, education/training on using the WHO checklist, the adaptation of the checklist to their department, their responsibilities in implementing and using the checklist, the frequency of use in emergency situations, and the impact on patient safety. Results The results of the study showed that assistant nurses, despite having the lowest level of education among healthcare professionals, were highly trusted and valued by other members of the surgical team. Most healthcare professionals were unsure who was responsible for using the WHO checklist but believed it was the assistant nurse's responsibility to ensure its implementation. Assistant nurses reported little to no training on using the checklist but noted that it had been adapted to the department's needs. Almost half (48.8%) of assistant nurses believed that the checklist was often used in emergency surgery, and most believed that it improved patient safety. Conclusions Improved understanding of the significance of assistant nurses in implementing the WHO Surgical Safety Checklist may enhance adherence to the checklist and potentially improve patient safety, as they were the most valued and trusted healthcare professionals in the surgical team according to the study's findings.