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Alexandr Ceasovschih,1,2,* Victorita Sorodoc,1,2 Annabelle Shor,1,* Raluca Ecaterina Haliga,1,2,* Lynn Roth,3 Catalina Lionte,1,2 Viviana Onofrei Aursulesei,4,* Oana Sirbu,1,2,* Nicolae Culis,5 Albina Shapieva,6 Mohammed AR Tahir Khokhar,1 Cristian Statescu,7 Radu A Sascau,7 Adorata Elena Coman,1 Alexandra Stoica,1,2 Elena-Daniela Grigorescu,1 Maciej Banach,8 Costas Thomopoulos,9 Laurentiu Sorodoc1,2 1Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, 700115, Romania; 2 2nd Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, Iasi, 700111, Romania; 3Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, 2610, Belgium; 4Department of Cardiology, Clinical Emergency Hospital “Sfantul Spiridon”, Iasi, 700106, Romania; 5Nottingham University Hospitals NHS Trust, Queen’s Medical Center, Nottingham, NG72UH, UK; 6Cardiac Electrophysiology Department, Petrovsky National Research Center of Surgery, Moscow, 119991, Russia; 7Department of Cardiology, Cardiovascular Diseases Institute “Prof. Dr. George I.M. Georgescu”, Iasi, 700503, Romania; 8Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, 93338, Poland; 9Department of Cardiology, Elena Venizelou General Hospital, Athens, GR-11522, Greece*These authors contributed equally to this workCorrespondence: Victorita Sorodoc, 2nd Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700111, Romania, Tel +40232 240 822, Email vivisorodoc@yahoo.com Lynn Roth, Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, 2610, Belgium, Email lynn.roth@uantwerpen.beAbstract: The Coronavirus Disease 2019 (COVID-19) pandemic was declared in early 2020 after several unexplained pneumonia cases were first reported in Wuhan, China, and subsequently in other parts of the world. Commonly, the disease comprises several clinical features, including high temperature, dry cough, shortness of breath, and hypoxia, associated with findings of interstitial pneumonia on chest X-ray and computer tomography. Nevertheless, severe forms of acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are not limited to the respiratory tract but also may be extended to other systems, including the cardiovascular system. The bi-directional relationship between atherosclerosis and COVID-19 is accompanied by poor prognosis. The immune response hyperactivation due to SARS-CoV-2 infection causes an increased secretion of cytokines, endothelial dysfunction, and arterial stiffness, which promotes the development of atherosclerosis. Also, due to the COVID-19 pandemic, access to healthcare amenities was reduced, resulting in increased morbidity and mortality in patients at risk. Furthermore, as lockdown measures were largely adopted worldwide, the sedentary lifestyle and the increased consumption of processed nutrients or unhealthy food increased, and in the consequence, we might observe even 70% of overweight and obese population. Altogether, with the relatively low ratio of vaccinated people in many countries, and important health debt appeared, which is now and will be for next decade a large healthcare challenge. However, the experience gained in the COVID-19 pandemic and the new methods of patients’ approaching have helped the medical system to overcome this crisis and will hopefully help in the case of new possible epidemics.Keywords: vascular diseases, COVID-19, SARS-CoV-2, endothelial dysfunction, atherosclerosis, arterial stiffness, vaccines

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

Introduction. Interstitial Cells of Cajal (ICCs) play a critical role in the regulation of gastrointestinal motility and have been implicated in various functional gastrointestinal disorders. Recent research indicates a possible association between ICCs and the tumor risk of Gastrointestinal Stromal Tumors (GISTs). This research aims to examine the clinical, histopathological, and biomolecular characteristics of ICCs and their relevance in assessing GIST risk. Materials and Methods. This study examined fourteen GIST patients who underwent surgical intervention at the Surgery Department of Carol Davila Nephrology Hospital in Bucharest. Parameters including age, gender, tumor location/ dimensions were scrutinized. Immunohistochemistry employing markers CD117, DOG-1, and CD34 was employed to ascertain the presence of ICCs and GISTs. Results. The GIST risk stratification revealed distribution with 35.71% very low-risk, 21.42% low-risk, 14.28% intermediate-risk, and 28.57% high-risk categories. Predominantly, 57.14% of cases fell within the very low-risk and low-risk categories. Positive immunoreactivity for CD117 and DOG-1 was noted in 92.86% of patients, while CD34 exhibited positivity in 85.71% of cases. Gastric GISTs manifested heightened marker expression. Notably, immunohistochemistry unveiled robust positivity for CD117, DOG-1, and CD34, illustrating a positive correlation between elevated ICC levels and high-risk GISTs. Conclusions. The findings propose an association between ICC levels and high-risk GISTs, accentuating the diagnostic utility of CD117, DOG-1, and CD34 markers in GIST assessment.

Abstract In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

Introducere. Sindromul metabolic (SM) reprezintă o asociere de alterări metabolice independente cu risc cardiovascular crescut. Receptorii activați de inductorii proliferării peroxizomilor-alpha (PPARα), membri ai superfamiliei receptorilor nucleari cu rol de factori de transcripţie , sunt implicați în reglarea metabolismului lipidic și inflamație în diferite tipuri de celule și reprezintă una din țintele terapeutice în SM. Am analizat expresia PPARα în leucocitele pacienților cu SM, îndreptându-ne spre implicarea PPARα în această patologie. Material și metoda. Studiul s-a desfășurat pe un număr de 57 pacienți adulți recrutați după semnarea consimțământului informat, investigați pentru evidențierea SM conform criteriilor Federației Internaționale de Diabet (IDF) și care au fost grupați în două loturi: lotul SM (26 pacienți) și lotul de control, fără SM (31 subiecți). Au fost determinați parametrii clinici și de laborator utilizați curent în evaluarea SM. În populațiile de leucocite circulante ale pacienților au fost evaluate nivelurile de expresie a două molecule, PPARα și CD36, printr-o metodă optimizată de citometrie în flux . Semnificația diferențelor dintre valorile parametrilor măsurați a fost stabilită prin analiza statistică, utilizând programul SPSS și teste statistice simple (Pearson, t-Student, Chi-test). Rezultate și discuții. Când am comparat nivelul de expresie a PPARα în eozinofile, am obținut a reducere semnificativă a intensității medie de fluorescență (p

This review aims to streamline the approach to assessing the most used valorization methods for fruit and vegetable waste (FVW) that are eco-friendly, cost-effective, and sustainable within a circular economy framework. Green processing technologies for the extraction of bioactive compounds from FVW, their applications, and the technico-economical assessment of FVW’ biorefinery to support circular economy are highlighted. Important value-added products generated by FVW include bioactive compounds, pectin, protein isolates, such as soy, natural pigments such as anthocyanins, quinones, carotenoids, betalains, and chlorophyll. At this time, the prospects of using FVW have increased in the food supplements, bioactive and edible food packaging, agriculture, energy, and water purification fields. The findings report that proper management of FVW not only minimizes their addition to landfills in the absence of composting, but also promotes the efficient utilization of resources for the development of innovative materials with a wide range of beneficial applications. Implementing the possible solutions described in this paper would not only reduce environmental impact, but also open up new economic opportunities through the valorization of FVW.

Since 2018, the TROPOspheric Monitoring Instrument (TROPOMI) on board the Sentinel-5 Precursor (S5P) has provided unprecedented images of nitrogen dioxide (NO2) tropospheric columns at a relatively high spatial resolution with a daily revisit. This study aims at assessing the potential of TROPOMI–PAL data to estimate the national to urban NOx emissions in France from 2019 to 2021, using the variational mode of the recent Community Inversion Framework (CIF) coupled to the CHIMERE regional transport model at a spatial resolution of 10 km × 10 km. The seasonal to inter-annual variations in the French NOx emissions are analyzed. Special attention is paid to the current capability to quantify strong anomalies in the NOx emissions at intra-annual scales, such as the ones due to the COVID-19 pandemic, by using TROPOMI NO2 observations. At the annual scale, the inversions suggest a decrease in the average emissions over 2019–2021 of −3 % compared to the national budget from the Copernicus Atmosphere Monitoring Service regional inventory (CAMS-REG) for the year 2016, which is used as a prior estimate of the national-scale emissions for each year by the Bayesian inversion framework. This is lower than the decrease of −14 % from 2016 to the average over 2019–2021 in the estimates of the French Technical Reference Center for Air Pollution and Climate Change (CITEPA). The lower decrease in the inversion results may be linked in large part to the limited level of constraint brought by the TROPOMI data, due to the observation coverage and the ratio between the current level of errors in the observation and the chemistry-transport model, and to the NO2 signal from the French anthropogenic sources. Focusing on local analysis and selecting the days during which the TROPOMI coverage is good over a specific local source, we compute the reductions in the anthropogenic NOx emission estimates by the inversions from spring 2019 to spring 2020. These reductions are particularly pronounced for the largest French urban areas with high emission levels (e.g., −26 % from April 2019 to April 2020 in the Paris urban area), reflecting reductions in the intensity of vehicle traffic reported during the lockdown period. However, the system does not show large emission decreases for some of the largest cities in France (such as Bordeaux, Nice and Toulouse), even though they were also impacted by the lockdown measures. Despite the current limitations for the monitoring of emissions at the national scale, or for some of the largest cities in France, these results open positive perspectives regarding the ability to support the validation or improvement of inventories with satellite observations, at least at the local level. This leads to discussions on the need for a stepwise improvement of the inversion configuration for a better extraction and extrapolation in space and time of the information from the satellite observations.

Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital anomaly defined by double discordance – atrioventricular and ventricular-arterial. ccTGA frequently has associated lesions, which influence long-term survival.

Abstract When antimicrobial resistant bacteria (ARB) and genes (ARGs) reach novel habitats, they can become part of the habitat’s microbiome in the long term if they are able to overcome the habitat’s biotic resilience towards immigration. This process should become more difficult with increasing biodiversity, as exploitable niches in a given habitat are reduced for immigrants when more diverse competitors are present. Consequently, microbial diversity could provide a natural barrier towards antimicrobial resistance by reducing the persistence time of immigrating ARB and ARG. To test this hypothesis, a pan-European sampling campaign was performed for structured forest soil and dynamic riverbed environments of low anthropogenic impact. In soils, higher diversity, evenness and richness were significantly negatively correlated with relative abundance of >85% of ARGs. Furthermore, the number of detected ARGs per sample were inversely correlated with diversity. However, no such effects were present in the more dynamic riverbeds. Hence, microbiome diversity can serve as a barrier towards antimicrobial resistance dissemination in stationary, structured environments, where long-term, diversity-based resilience against immigration can evolve.

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

In addition to the infectious disease, the COVID-19 pandemic was accompanied by an infodemic that worsened the outbreak. Increased digital health literacy (DHL) skills and information-seeking behaviors are crucial for accessing, understanding, and evaluating online health information, especially during a pandemic, where misinformation imposes immediate health consequences. This study explores the predictors of DHL among Romanian students and their information-seeking behaviors during the COVID-19 pandemic. Data was collected through a cross-sectional study design over 3 months (December 2020–February 2021) and a self-reported web-based questionnaire from 1,381 university students from Romania assessing DHL and information-seeking behaviors. We used descriptive statistics, Cronbach Alpha coefficients, and univariate and multivariate binary logistic regressions to explore DHL’s predictors in the Romanian sample. Results showed that overall, the study sample had high levels of DHL. However, almost half of the respondents reported having problems assessing whether the information searched related to coronavirus is reliable or not, and 95% shared someone else’s private information online. Age, subjective social status, gender, and chronic diseases were identified as predictors for DHL. Students’ DHL skills need to be strengthened using tailored educational programs and interventions emphasizing the quality, accuracy, and timely provision of online information on official public health platforms. Additional actions include fostering collaborations between educational institutions and public health authorities, alongside developing smartphone applications for real-time guidance on health topics. It is of the utmost importance to address the spread of the infodemic through different strategies, to combat misinformation among university students.

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.

Populist governments aim to fundamentally challenge the EU, raising the question of when and how backsliding populist governments disrupt decision-making in the Council of the EU (hereafter Council). Due to their anti-elite and strong anti-EU stance, along with their opposition to core values of liberal democracy, I argue that these governments are more inclined to resort to unpolitics, understood as “unsettlement.” Analysing the behaviour of the Hungarian Fidesz government in the Council, the article demonstrates that populist governments resort to unpolitics but use an à la carte approach. Populist backsliding governments selectively oppose the Council’s formal and informal decision-making rules. Looking at the voting behaviour in the Council since 2009, the article shows that the Fidesz government preserves the norm of consensus. However, over time, it has become the government that has most often broken with this norm. Conversely, when it comes to “backsliding-inhibiting competences,” the Fidesz government challenges both formal and informal rules through a wide range of strategies, i.e., systematically contesting the legality of procedures and decisions, embracing a confrontational approach and diplomacy, self-victimisation, bending the truth, and accusatory rhetoric. To illustrate them, the article focuses on decisions related to the dismantlement of the rule of law in the country, such as Article 7 TEU, the application of Regulation 2020/2092, and the disbursement of Cohesion funds.

IntroductionIn a globalized and constantly evolving employment environment, it is imperative that organizations cultivate effective employer branding strategies to maintain competitiveness and attractiveness. These would allow them to obtain unique advantages in the market but also support for the internal employer brand. Despite the critical role of employer branding in attracting and retaining top talent, there remains a gap in understanding its relationship to HRM practices and employee perceptions of those practices. The purpose of this research was to investigate the correlation between human resources management practices and employer branding measured through organizational attractiveness and seen from the employees’ perspective. Additionally, to find out if there is a significant difference between the private and public sector in terms of the perception of HRM practices influencing organizational attractiveness.MethodsA questionnaire was applied to 800 respondents, employed in various positions in private and public sector organizations in western Romania. Two scales were applied to evaluate human resources management practices and the employer’s attractiveness from the employees’ perspective.ResultsFindings indicate a direct and positive relation between HRM practices and organizational attractiveness, with particular emphasis on performance appraisal practice, training and development, and work-life balance practices. When it comes to private sector, the significant practices influencing organizational attractiveness are performance appraisal, safety, and work-life balance practices, whereas in the public sector we have training-development and performance appraisal practices.DiscussionThese results underline the role of human resource management in strengthening internal support for the employer brand and increasing overall employer attractiveness. The more appropriate human resource management practices are in the perception of employees, the more attractive the organization is perceived as an employer.