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Glioblastoma stem cells (GSCs) are key drivers of relapse, metastasis, and therapy resistance in glioblastoma due to their adaptability and diversity, which make them challenging to target effectively. This study explores the O-glycosylation in differentiating two key GSC subtypes, CD133 and CD44. We utilized the TCGA dataset of GBM and presented the reproducible bioinformatics analysis for our results. Our profiling showed enriched O-glycosylation signatures in CD44-expressing GBM cells over CD133, with Cosmc, the chaperone for core mucin-type O-glycosylation, significantly upregulated in the CD44-positive group. Moreover, Cosmc was associated with shorter progression-free intervals, suggesting its potential as an indicator of aggressive disease. High Cosmc expression also enriched immune-related pathways, including inflammatory response and antigen presentation, and was associated with presence of myeloid cells, T cells, and NK cells. Additionally, elevated Cosmc correlated with extracellular matrix (ECM) pathways and stromal cell populations, such as perivascular fibroblasts. These findings position O-glycosylation, specially, Cosmc as a promising biomarker for distinguishing GSC subclones, with relevance to immune modulation, and ECM dynamics, identifying it as a potential target for novel GBM therapies.

Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.

Abstract Background Despite the prevalence of distance learning during COVID-19, conducting clinical training for nursing students remains challenging. In compliance with social-distancing restrictions, a Zoom-based virtual OSCE preparation program for nursing students was designed, and it included clinical skills. The aims of this study were to assess nursing students’ satisfaction with a virtual program for Objective Structured Clinical Examination (OSCE) preparation, and to evaluate its learning outcomes measured by OSCE scores as compared to those of in-person preparation programs. Methods A descriptive and repeated cross-sectional study was designed. Students’ satisfaction with the virtual program was based on a post-course survey and personal reflections. OSCE scores of graduates of the virtual program (n = 82) tested in 2021 were compared to those of 337 graduates of in-person programs tested in 2017–2020. Results A post-program survey revealed that 88% of the students in 2021 were satisfied with the virtual program and felt it prepared them properly for the OSCE (26% agree and 62% strongly agree). No significant differences were found between OSCE scores following the virtual program conducted in 2021 and scores following in-person programs conducted in 2017–2020. Conclusions This study suggests that nursing education can benefit from integrating virtual programs which incorporate clinical practices into the curricula, without harming student competency. The study results may address the problem of maintaining clinical practices in a time of limited accessibility, and in settings of low resources. It is important to expand the investigation to long-term impact of virtual training programs on nursing students’ competencies.

Abstract Background Evidence has shown that restrictions during the COVID-19 pandemic have negatively affected breastfeeding support and outcomes in hospitals in many countries. The aims of the study were to describe exclusive breastfeeding rates and identify factors associated with exclusive breastfeeding at hospital discharge among women who gave birth during the COVID-19 pandemic in Israel. Methods A cross-sectional online anonymous survey based on WHO standards for improving quality of maternal and newborn care in health facilities was conducted among a sample of women who gave birth to a healthy singleton infant in Israel during the pandemic (between March 2020 and April 2022). The socio-ecological approach was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with exclusive breastfeeding at hospital discharge according to women perspectives. Results Among the 235 Israeli participants, 68.1% exclusively breastfed, 27.7% partially breastfed, and 4.2% did not breastfeed at discharge. Results of the adjusted logistic regression model showed that factors significantly associated with exclusive breastfeeding were the intrapersonal factor of multiparity (adjusted OR 2.09; 95% Confidence Interval 1.01,4.35) and the organizational factors of early breastfeeding in the first hour (aOR 2.17; 95% CI 1.06,4.45), and rooming-in (aOR 2.68; 95% CI 1.41,5.07). Conclusions Facilitating early breastfeeding initiation and supporting rooming-in are critical to promoting exclusive breastfeeding. These factors, reflecting hospital policies and practices, along with parity, are significantly associated with breastfeeding outcomes and highlight the influential role of the maternity environment during the COVID-19 pandemic. Maternity care in hospitals should follow evidence-based breastfeeding recommendations also during the pandemic, promoting early exclusive breastfeeding and rooming-in among all women, with particular attention to providing lactation support to primiparous women. Trial registration Clinical Trials NCT04847336.

Given advancements in large-scale data and AI, integrating multimodal artificial intelligence into cancer research can enhance our understanding of tumor behavior by simultaneously processing diverse biomedical data types. In this review, we explore the potential of multimodal AI in comprehending B-cell non-Hodgkin lymphomas (B-NHLs). B-cell non-Hodgkin lymphomas (B-NHLs) represent a particular challenge in oncology due to tumor heterogeneity and the intricate ecosystem in which tumors develop. These complexities complicate diagnosis, prognosis, and therapy response, emphasizing the need to use sophisticated approaches to enhance personalized treatment strategies for better patient outcomes. Therefore, multimodal AI can be leveraged to synthesize critical information from available biomedical data such as clinical record, imaging, pathology and omics data, to picture the whole tumor. In this review, we first define various types of modalities, multimodal AI frameworks, and several applications in precision medicine. Then, we provide several examples of its usage in B-NHLs, for analyzing the complexity of the ecosystem, identifying immune biomarkers, optimizing therapy strategy, and its clinical applications. Lastly, we address the limitations and future directions of multimodal AI, highlighting the need to overcome these challenges for better clinical practice and application in healthcare.

Abstract Background Exclusive breastfeeding is the optimal infant nutrition, providing infants immunoprotection against many diseases including SARS-CoV-2 infection. Restrictions during the COVID-19 pandemic may have negatively affected breastfeeding practices in maternity care facilities. The aims of the study were to examine exclusive breastfeeding rates at discharge over time and to identify factors associated with exclusive breastfeeding during the pandemic. Methods A cross-sectional survey was conducted among mothers who gave birth in a maternity care facility in the World Health Organization (WHO) European Region countries during the COVID-19 pandemic. The socio-ecological model was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with maternal report of exclusive breastfeeding at the time of discharge. Results There were 26,709 participating mothers from 17 European Region countries who were included in the analysis. Among the mothers, 72.4% (n = 19,350) exclusively breastfed and 27.6% (n = 7,359) did not exclusively breastfeed at discharge. There was an overall decline in exclusive breastfeeding rates over time (p = 0.015) with a significantly lower rate following the publication of the WHO breastfeeding guidelines on 23 June 2020 (AOR 0.88; 95% CI 0.82, 0.94). Factors significantly associated with exclusive breastfeeding outcomes in the logistic regression analysis included maternal age, parity, education, health insurance, mode of birth, inadequate breastfeeding support, lack of early breastfeeding initiation, lack of full rooming-in, birth attendant, perceived healthcare professionalism and attention, facility room cleanliness, timing of birth, and location of birth. Conclusions Results from the study indicate the decline in exclusive breastfeeding rates in the WHO European Region during the COVID-19 pandemic. Using the socio-ecological model to identify factors associated with breastfeeding outcomes facilitates an integrated and holistic approach to address breastfeeding needs among women across the region. These findings demonstrate the need to augment breastfeeding support and to protect exclusive breastfeeding among mother-infant dyads, in an effort to reverse the declining exclusive breastfeeding rates. The study highlights the need to educate mothers and their families about the importance of exclusive breastfeeding, reduce maternal-infant separation, increase professional breastfeeding support, and follow evidence-based practice guidelines to promote breastfeeding in a comprehensive and multi-level manner. Trial registration number Clinical Trials NCT04847336.

Abstract Background Fear of falling (FoF) is an important risk factor for falls among older people. The objectives of our investigations were: a.) to present characteristics of older community-dwelling (CD) fallers with persistent or transient FoF (P-FoF or T-FoF) over 12 months, and b.) to investigate clinical predictors of P-FoF and T-FoF and c.) to explore differences between P-FoF and T-FoF. Methods Our series consisted of 389 older people reporting a fall or injurious fall at baseline and during 24 months follow-up participating in a multicenter prospective study. T-FoF was defined as participants reported “not at all” at baseline and “somewhat/fairly/very concerned” at follow-up, or “not at all” at follow-up, and “somewhat/fairly/very concerned” at baseline, and P-FoF was defined as participants answered “somewhat/fairly/very concerned” in both assessments at baseline and at follow-up. The association between risk factors and T-FoF or P-FoF was investigated by logistic regression analysis. Results The mean age of fallers in our sample was 79.0 years (SD 6.0), and 54.2% were females. Out of 389 older adults with a fall history at baseline, 83 participants (21.3%) did not report any FoF over time, P-FoF and T-FoF were observed in 42.7% and 35.9% of participants, respectively. After adjusting for potential confounders (e.g. age, gender), osteoporosis (OR = 2.04, 95%CI = 1.03–4.05) and impaired physical performance (OR = 2.38, 95%CI = 1.12–5.03) were significant predictors of T-FoF vs No-FoF. Osteoporosis (OR = 2.68, 95%CI = 1.31–5.48), depressive symptoms (OR = 3.54, 95%CI = 1.23–10.1) and living alone (OR = 2.44, 95%CI = 1.17–5.06) were significantly associated with P-FoF vs No-FoF. When comparing T-FoF and P-FoF, female gender (OR = 1.95, 95%CI = 1.16–3.27), BMI (OR = 1.08, 95%CI = 1.02–1.14), overall comorbidity (OR = 1.07, 95%CI = 1.02–1.13) and depression (OR = 2.55, 95%CI = 1.33–4.88) were significant predictors of P-FoF. Conclusions T-FoF and P-FoF may be predicted by different sets of risk factors among older fallers. Thus, fallers should be screened for FoF especially when carrying specific risk factors, including female gender, osteoporosis, depression, living alone, impaired physical performance, BMI, comorbidity. These findings may be helpful in designing tailored intervention to blunt the risks related to consequence of FoF among older people experiencing falls. Trial registration The SCOPE study was registered prospectively at clinicaltrials.gov (NCT02691546; 25/02/2016).

Abstract Background Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM. Methods A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses. Results A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08–1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71–0.89 were associated with the presence of sarcopenia. Conclusions One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique ability to mediate inflammatory responses of the immune system. Given the critical role of DCs in shaping immunity, they present an attractive avenue as a therapeutic target to program the immune system and reverse immune disease disorders. To ensure appropriate immune response, DCs utilize intricate and complex molecular and cellular interactions that converge into a seamless phenotype. Computational models open novel frontiers in research by integrating large-scale interaction to interrogate the influence of complex biological behavior across scales. The ability to model large biological networks will likely pave the way to understanding any complex system in more approachable ways. We developed a logical and predictive model of DC function that integrates the heterogeneity of DCs population, APC function, and cell-cell interaction, spanning molecular to population levels. Our logical model consists of 281 components that connect environmental stimuli with various layers of the cell compartments, including the plasma membrane, cytoplasm, and nucleus to represent the dynamic processes within and outside the DC, such as signaling pathways and cell-cell interactions. We also provided three sample use cases to apply the model in the context of studying cell dynamics and disease environments. First, we characterized the DC response to Sars-CoV-2 and influenza co-infection by in-silico experiments and analyzed the activity level of 107 molecules that play a role in this co-infection. The second example presents simulations to predict the crosstalk between DCs and T cells in a cancer microenvironment. Finally, for the third example, we used the Kyoto Encyclopedia of Genes and Genomes enrichment analysis against the model’s components to identify 45 diseases and 24 molecular pathways that the DC model can address. This study presents a resource to decode the complex dynamics underlying DC-derived APC communication and provides a platform for researchers to perform in-silico experiments on human DC for vaccine design, drug discovery, and immunotherapies.

Abstract Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse and niche. Despite the extensive characterization of FL epigenetic signature and TME, the functional consequences of epigenetic dysregulation on TME and niche plasticity need to be better characterized. In this review, first we describe the most frequent epigenomic alterations in FL (KMT2D, CREBBP and EZH2) that affect the immunological niche, and their potential consequences on the informational transfer between tumor B cells and their microenvironment. Then, we discuss the latest progress to harness epigenetic targets for inhibiting the FL microenvironment. Finally, we highlight unexplored research areas and outstanding questions that should be considered for a successful long-term treatment of FL.

Abstract CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immune-related diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug response analysis of existing FDA-approved drugs and compounds. Integration of disease-specific differentially expressed genes with altered reactions in response to metabolic perturbations identified 68 drug targets for the three autoimmune diseases. In vitro experimental validation, together with literature-based evidence, showed that modulation of fifty percent of identified drug targets suppressed CD4+ T cells, further increasing their potential impact as therapeutic interventions. Our approach can be generalized in the context of other diseases, and the metabolic models can be further used to dissect CD4+ T-cell metabolism.

Abstract Background Chronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over. Methods Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study,were used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE ( 5/≤5). Results In total, 63% of the population had an eGFR

Abstract Background Different mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD. Methods In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation. Results We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF 60 (OR = 2.95, 95%CI = 1.77–4.94 for MNA

Abstract Background Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79–1.14 for eGFR

Abstract Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR

Perjanjian pinjam nama atau biasanya dikenal dengan istilah perjanjian nominee merupakan salah satu upaya dari warga asing agar bisa memperoleh hak kepemilikan tanah di Negara Kesatuan Republik Indonesia melalui cara meminjam nama warga Negara Indonesia, kemudian dimasukkan pada sertifikat kepemilikan yang mana seluruh pembiayaan ditanggung oleh pihak warga negara asing. Peraktik pinjam nama ini bukan suatu hal yang asing lagi oleh masyarakat Indonesia dan merupakan bentuk penyelundupan hukum tanah, mengingat adanya ketentuan Undang-Undang Nomor 5 Tahun 1960 Tentang Peraturan Dasar Pokok-Pokok Agraria pada Pasal 21 Ayat (1) yang menyebutkan “Hanya Warga Negara Indonesia yang mempunyai hak milik”. Tujuan penelitian agar dapat memahami apakah Perjanjian nominee selaras dengan hukum positif Indonesia dan bagaimana penerapan asas kebangsaan dalam perjanjian nominee. Metode yang dipakai oleh penelitian ini adalah metode penelitian normative yang lebih menitikberatkan pada pendekatan Perundang-undangan dan konseptual. Kesimpulan dari penelitian ini bahwa perjanjian nominee tidak selaras oleh peraturan yang berlaku di Negara Kesatuan Republik Indonesia disebabkan melanggar persyaratan suatu perjanjian berupa causa yang halal dan melanggar asas perjanjian yaitu asas kebebasan berkontrak dan berakibat batal demi hukum. Kemudian, penerapan asas kebangsaan dalam perjanjian nominee tidak tepat dan sangat bertentangan disebabkan tidak memenuhi syarat yang tertuang dalam Pasal 9 Ayat (1) dan (2).

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1–positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3+ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen–specific CD8+ T cells and PD-1+Tim-3+ CD8+ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8+ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8+ T cells impeded the trogocytosis of CD8+ TILs in vivo. Trogocytosed CD8+ T cells presented tumor peptide–major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.

Objectives Develop and validate a WHO Standards-based online questionnaire to measure the quality of maternal and newborn care (QMNC) around the time of childbirth from the health workers’ perspective.Design Mixed-methods study.Setting Six countries of the WHO European Region.Participants and methods The questionnaire is based on lessons learnt in previous studies, and was developed in three sequential phases: (1) WHO Quality Measures were prioritised and content, construct and face validity were assessed through a Delphi involving a multidisciplinary board of experts from 11 countries of the WHO European Region; (2) translation/back translation of the English version was conducted following The Professional Society for Health Economics and Outcomes Research guidelines; (3) internal consistency, intrarater reliability and acceptability were assessed among 600 health workers in six countries.Results The questionnaire included 40 items based on WHO Standards Quality Measures, equally divided into four domains: provision of care, experience of care, availability of human and physical resources, organisational changes due to COVID-19; and its organised in six sections. It was translated/back translated in 12 languages: Bosnian, Croatian, French, German, Italian, Norwegian, Portuguese, Romanian, Russian, Slovenian, Spanish and Swedish. The Cronbach’s alpha values were ≥0.70 for each questionnaire section where questions were hypothesised to be interrelated, indicating good internal consistence. Cohen K or Gwet’s AC1 values were ≥0.60, suggesting good intrarater reliability, except for one question. Acceptability was good with only 1.70% of health workers requesting minimal changes in question wording.Conclusions Findings suggest that the questionnaire has good content, construct, face validity, internal consistency, intrarater reliability and acceptability in six countries of the WHO European Region. Future studies may further explore the questionnaire’s use in other countries, and how to translate evidence generated by this tool into policies to improve the QMNC.Trail registration number NCT04847336

Exploration is essential to ensure the achievement of the UN Sustainable Development Goals through the provision of ferrous and non-ferrous metal resources. At the same time, geology as an industry should be based on the principles of sustainable development. The purpose of the study is to develop and test the technology of aeromagnetic survey for prospecting for iron ores that meets the requirements of the sustainable development of modern geology. Unmanned aerial vehicles with GNSS receivers, a camera, a magnetometer, as well as Trimble Business Center, Agisoft Metashape Professional, and QM Center software were used. A search for magnetic radiation anomalies over an area of 6.20 square kilometres was carried out. Areas were established where the radiation level is 59000–65860 nanotesl (background – 57803 nanotesl), that is, there are reserves of magnetite ores. The binding of these sites to the exact geographical coordinates has been completed. The results of the low-altitude aeromagnetic survey are compared with the control data of the ground-based magnetic survey performed earlier, and the correctness of the low-altitude aeromagnetic survey data is shown. Since ground surveys provide more detailed information, it is advisable to use low-altitude aeromagnetic surveys as a method of fast, low-cost screening of large areas. This will make it possible to make decisions on the expediency of carrying out expensive ground works. The study found that labour productivity in low-altitude aeromagnetic surveys exceeds that in ground-based surveys by about 75 times. In addition, low-altitude aeromagnetic surveys have virtually no impact on ecosystems and do not lead to greenhouse gas emissions. This corresponds to the main directions of sustainable development of geology.

One of the serious environmental problems is the eutrophication of water bodies, so monitoring of this process is necessary. The purpose of the study is to assess the level of eutrophication of coastal waters based on the analysis of satellite imagery data using NDVI. The NDVI value and the water area where NDVI is greater than zero were used as indicators of eutrophication. The study was carried out in the Gdansk and Kaliningrad bays of the Baltic Sea. Computer processing of images in .tif (NDVI) and .png (RGB images) formats from satellites of the Sentinel-2 and Landsat family for 2013-2021 was performed. As a result of the study, it was found that the calculation of the NVDI index and the area where this index is greater than zero is an adequate method for monitoring eutrophication, since it demonstrates areas of the water area where a high level of vegetation is observed. Compared to the calculation of chlorophyll content indices (which are very difficult to establish standard values), the calculation of NDVI is easier to interpret. The study shows that the level of eutrophication in the bays of the Baltic Sea depends on seasonality, it usually increases from May to August, and decreases in September. Annual fluctuations are also observed, in particular, a decrease in eutrophication in 2020-2021 due to the decline in economic activity and anthropogenic pollution. Sharp and rapid increases in the level of eutrophication were found, but in the study period, the ecosystems of the bays were capable of self-healing.

The Krapivinsky hydroelectric complex is a project that was a complex of more than 40 events. Their full-scale implementation could prevent those environmental problems that are especially acute for Kuzbass today. The production of electricity at the Krapivinsky HPS was supposed to be an incidental process accompanying the environmental project to a greater extent. However, in order to make a decision on the future fate of this object, it is necessary to assess the impact on the environment, including flora within the territorial boundaries of the Krapivinsky reservoir, assessing the possible damage to vegetation in the water protection zone and in the flood zone. This is especially true for rare plant species listed in the Red Book of the Russian Federation and the Kemerovo region - Kuzbass. For this purpose, an analysis of the vegetation on the territory of the object under consideration was carried out, the species of the presented plants were studied and examined, it was determined whether they were classified as rare species, and ways were also proposed to minimize possible harmful or irreversible damage to the flora in the zone of the Krapivinsky HPS.

The object of research is the relations that develop regarding the raw material rent and the relations regarding the digital rent in this publication. The purpose of the study is to compare the categories of raw material and digital rent in the mining industry. The work was methodologically based on the use of the following methods: analysis and synthesis, deduction and induction, and the system approach. It was revealed that mining enterprises in the context of the digital revolution become the owners of two types of rents: raw materials and digital, which means the complication of budgetary relations with the state. To determine the nature of these relations, the need to compare the foundations, nature, and forms of manifestation of raw material and digital rents was shown. Conclusions were drawn in the work. It is determined that the cause of raw material rent is the right of ownership of land, and digital rent is the network effect, that is, the specifics of technology. It is emphasized that there are three subjects in classical rent relations: capitalists, while consumers and producers of digital products are present in digital rent relations. It is shown that the relations that develop regarding the raw material rent have a longer character of action compared to the relations regarding the digital rent. It is substantiated that the relations that develop over the raw material rent are formed only in the sphere of the use of natural resources, while the relations regarding the digital rent exist in any part of the digital economy. It is presented that the origin and movement of raw material rent is weakly related to technological progress, while digital rent has grown directly from the digital revolution. It is revealed that the phenomenon of digital rent is based on a special resource – creative

The paper features digital technologies in satellite farming and introduces a quantitative methodology to evaluate various types of their effectiveness. The authors determined the main types of efficiency and components of evaluation and substantiated the algorithm of analysis. The paper also contains a list of related economic, environmental, and social components, as well as a set of formulas and dependencies. The methodology for assessing the effectiveness of digital technologies has a two-block structure. The first block determines the needs and opportunities for the implementation of digital technologies and helps to define the enterprises that may benefit from digital technologies. The second block involves a direct evaluation of the results and efficiency of the digital technologies to be implemented and substantiates management solutions. The paper describes approaches and procedures that help to assess the biological, technological, and economic benefits of digital technologies for an agricultural enterprise. The authors quantified the structure of the environmental effect of the introduction of digital technologies and introduced some dependencies can determine profitability and cost recovery indicators. The research used the methodological approach to assess the environmental and social efficiency of digital technologies for an agricultural enterprise. The approach corresponds with the requirements of sustainable agricultural development declared by the UN. The results can be used by enterprises of the agro-industrial complex and suppliers of digital technologies.

This study aimed to investigate the effect of an enrichment program based on using (V) shape map in teaching the Research Methods course on developing scientific research skills and critical thinking skills among students of the College of Educational Sciences at Zarqa University compared to the traditional method. The study was limited to female students registered in the Research Methods course, who were 78 students, and distributed in two classes. One was randomly selected as the experimental group, consisting of 40 students who were taught by using the (V) shape map. The other class was the control group and consisted of 38 students; they were taught by using the traditional method. Using ANOVA analysis, the study results showed that experimental group members showed more improvement in their scientific and critical thinking skills than the control group members, which was statistically significant at (P

This study aimed to investigate the effect of an enrichment program based on using (V) shape map in teaching the Research Methods course on developing scientific research skills and critical thinking skills among students of the College of Educational Sciences at Zarqa University compared to the traditional method. The study was limited to female students registered in the Research Methods course, who were 78 students, and distributed in two classes. One was randomly selected as the experimental group, consisting of 40 students who were taught by using the (V) shape map. The other class was the control group and consisted of 38 students; they were taught by using the traditional method. Using ANOVA analysis, the study results showed that experimental group members showed more improvement in their scientific and critical thinking skills than the control group members, which was statistically significant at (P

In organic viticulture, copper-based fungicides are commonly used to suppress Downy Mildew infection, caused by the oomycete Plasmopara viticola. However, the frequent and intensive use of such fungicides leads to accumulation of the heavy metal in soil and nearby waters with adverse effects on the ecosystem. Therefore, alternative, organic fungicides against Downy Mildew are urgently needed to reduce the copper load in vineyards. In this study, the use of Warburgia ugandensis Sprague (Family Canellacea) leaf and bark extracts as potential fungicides against Downy Mildew were evaluated. In vitro (microtiter) and in vivo (leaf discs, seedlings) tests were conducted, as well as field trials to determine the efficacy of the extracts against Downy Mildew. The results revealed an MIC100 of 500 µg/mL for the leaf extract and 5 µg/mL for the bark extract. Furthermore, experiments with leaf discs and seedlings demonstrated a strong protective effect of the extracts for up to 48 h under (semi-) controlled conditions. However, in field trials the efficacy of the extracts distinctly declined, regardless of the extracts’ origin and concentration.

Launch of the process of decarbonization of the economy and ratification of the Paris Climate Agreements in 2015-2016 puts the world’s coal industry in a difficult position. The purpose of the study is to identify the features of the development of the global coal industry, including regional ones, in anticipation of the active decarbonization of the world economy. For this, a quantitative analysis of the dynamics and structure of world coal production in 2010-2020 was carried out. As a result, it was revealed that the impact of the 2020 crisis did not become decisive for production. It can be compared to a price shock or the start of implementation of the Paris Climate Agreements. Some of the dynamics of the global coal production indicator is characterized by a weak declining trend (about minus 0.05% per year), although this indicator is generally unstable. The dynamics of coal production is characterized by the absence of an internal trend of self-development; autocorrelation is observed. The dynamics of coal production reacts to external shocks, while the regional differentiation of this indicator is growing. For 2010-2020 the share of North America and Europe fell to 13%, and the Asia-Pacific region – increased to 75%. Most developed countries are striving to reduce the production and consumption of coal (in the USA, Germany, Poland – by 25-50%), but many developing countries (India, Indonesia, Vietnam, Mongolia) are rapidly increasing production (by 30-70%). This is due to the possibility of exporting and using relatively cheap local fuel for economic development. Therefore, in the medium term, global coal production will remain stable with growing regional differentiation.

The use of unmanned aerial vehicles (hereinafter referred to as “UAV”) is one of the most popular ways of collecting objective spatial data on the land plots under survey. The main advantages of UAVs include the significantly lower cost of surveying, design and complex cadastral works compared to traditional methods of determining coordinates (e.g. performing a tacheometric survey and plane-table survey). The designed sector of block No. 9 in the Yurga urban district of Kemerovo region with cadastral No. 42:36:0102001 (land category: residential), comprising 22 apartment buildings, is taken as an example. The economic performance of land plots marking, carried out with cadastral accuracy, based on data obtained using UAVs and without the use thereof, is assessed.

The purpose of the study is to develop a forecast for the development of the coal industry in Russia for 2021-2030 in the context of the transition to carbon neutrality. Irwin’s criterion was used to analyze outliers of a number of dynamics, the method of ascending and descending series to identify a trend, standard methods for assessing autocorrelation and heteroscedasticity. For forecasting, the equations of trends, the method of exponential smoothing were used. The necessity of constructing a differentiated forecast for three elements of the use of coal mined in Russia is shown: domestic consumption, export to Europe, export to the Asia-Pacific region. Domestic coal consumption is very stable and with a 95% probability it will be between 210 and 225 million tons. Coal exports to the west will decline monotonically in line with plans by European governments to stop using thermal coal. It will be about 60 million tons in 2025 and about 15-20 million tons in 2030. Exports to the countries of the Asia-Pacific region will grow until 2030. After 2030, demand for thermal coal in the Asia-Pacific region will begin to decline in line with China's plans to move towards carbon neutrality by 2050-2060. According to the forecast obtained in the study, the export of coal from Russia to the east will reach 150 million tons in 2025 and 190 million tons in 2030, after which it will begin to decline. Therefore, the coal-mining regions of Russia in the next 5-10 years must diversify the economy.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass database, we demonstrate that patients expressing high levels of heparanase display elevated expression of proteins involved in chromatin remodeling and several oncogenic factors compared to patients expressing low levels of heparanase. These signatures were consistent with the known function of heparanase in driving tumor progression. Chromatin opening and downstream target genes were abrogated by inhibition of heparanase. Enhanced levels of heparanase in myeloma cells led to a dramatic increase in phosphorylation of PTEN, an event known to stabilize PTEN, leading to its inactivity and loss of tumor suppressor function. Collectively, this study demonstrates that heparanase promotes chromatin opening and transcriptional activity, some of which likely is through its impact on diminishing PTEN tumor suppressor activity.

We exploited the advantages of genomic in situ hybridization (GISH) to monitor the introgression process at the chromosome level using a simple and robust molecular marker in the interspecific breeding of bulb onion (Allium cepa L.) that is resistant to downy mildew. Downy mildew (Peronospora destructor [Berk.] Casp.) is the most destructive fungal disease for bulb onions. With the application of genomic in situ hybridization (GISH) and previously developed DMR1 marker, homozygous introgression lines that are resistant to downy mildew were successfully produced in a rather short breeding time. Considering that the bulb onion is a biennial plant, it took seven years from the F1 hybrid production to the creation of S2BC2 homozygous lines that are resistant to downy mildew. Using GISH, it was shown that three progeny plants of S2BC2 possessed an A. roylei homozygous fragment in the distal region of the long arm of chromosomes 3 in an A. cepa genetic background. Previously, it was hypothesized that a lethal gene(s) was linked to the downy mildew resistance gene. With the molecular cytogenetic approach, we physically mapped more precisely the lethal gene(s) using the homozygous introgression lines that differed in the size of the A. roylei fragments on chromosome 3.

Carnosic acid, a diterpene of Rosemarinus officinalis leaves extract (RE), has potent antioxidant activity in vitro. The dopaminergic connection of substantia nigra pars compacta to the hippocampus might be affected by oxidative stress which caused cognitive impairment observed in the early phase of Parkinson's disease (PD). Adult male Wistar rats were lesioned bilaterally by intra-nigral injection of 6-OHDA, and divided into six groups: four groups that orally given RE containing 40% of carnosic acid, at doses of 25, 50 and 100 mg/kg (treated rats) and distilled water (H2O), once daily for a period of 14 days before and after the injury. There were also two another groups as control rats which injected by normal saline and untreated lesion group. The injured animals were evaluated for their spatial memory performance by Morris Water Maze test. Lesioned rats showed significant increase in escape latency, as compared with control group. Two weeks after injury, tissue samples were collected from the hippocampus. Levels of catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) were determined. There were significant increase of SOD, GPX and CAT enzymes activities in RE50 treated group as compared to lesioned rats. We found a significant decrease of ROS in RE50 treated group as compared to Lesioned rats. These findings provide evidence that 50 mg/kg of RE decreased oxidative damage of the hippocampus induced by 6-OHDA and serve as potential candidate for the treatment of PD.

Abstract:Asimple and sensitive reversed-phase, ion-pair HPLC method was developed and validated for the simultaneous determination of B-group vitamins, thiamine chloride hydrochloride (B1), nicotinamide (B3), pyridoxine hydrochloride (B6) and folic acid in Pentovit® coated tablets. The cyanocobalamine (B12) was determined separately, because of its low concentration in the investigated multivitamin preparation. RP-HPLC analysis was performed with a LKB 2150 HPLC system, equipped with a UV/VIS Waters M484 detector. The procedures for the determination of B1, B2, B6 and folic acid were carried out on a Supelcosil ABZ+ (15 cm 4.6 mm; 5 µm) column with methanol-5mM heptanesulphonic acid sodium salt 0.1%triethylamine TEA(25:75 V/V); pH 2.8 as themobile phase. For the determination of B12 a Suplex pKb-100 (15 cm 4.6 mm; 5 µm) column andmethanolâwater (22:78 V/V) as themobile phase were used. The column effluentsweremonitored at 290 nm for B 1, B3, B6 and folic acid, and at 550 nm for B12. The obtained results and statistical parameters for all the investigated vitamins of the B-group in Pentovit® coated tablets were satisfactory and ranged from 90.4 % to 108.5 % (RSD. from 0.5% to 4.1 %). The parameters for the validation of the methods are given.

Abstract Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. We leveraged summary-level data of genome-wide association studies (PTSD: N = 1,222,882; atrial fibrillation (AF): N = 482,409; coronary artery disease (CAD): N = 1,165,690; hypertension (HT): N = 458,554; heart failure (HF): N = 977,323). First, we estimated genetic correlations and utilized genomic structural equation modeling to identify a common genetic factor for PTSD and CVD. Next, we assessed biological, behavioural, and psychosocial factors as potential mediators. Finally, we employed multivariable Mendelian randomization to examine causal pathways between PTSD and CVD, incorporating the same potential mediators. Significant genetic correlations were found between PTSD and CAD, HT, and HF (r g = 0.21-0.32, p ≤ 3.08 · 10−16), but not between PTSD and AF. Insomnia, smoking, alcohol dependence, waist-to-hip ratio, and inflammation (IL6, C-reactive protein) partly mediated these associations. Mendelian randomization indicated that PTSD causally increases CAD (IVW OR = 1.53, 95% CIs = 1.19-1.96, p = 0.001), HF (OR = 1.44, CIs = 1.08-1.92, p = 0.012), and to a lesser degree HT (OR = 1.25, CIs = 1.05-1.49, p = 0.012). While insomnia, smoking, alcohol, and inflammation were important mediators, independent causal effects also remained. In addition to shared genetic liability between PTSD and CVD, we present strong evidence for causal effects of PTSD on CVD. Crucially, we implicate specific lifestyle and biological mediators (insomnia, substance use, inflammation) which has important implications for interventions to prevent CVD in PTSD patients.

The physical education teacher has the obligation to form the representative team of the school unit to be enrolled in the competition provided in the sports calendar, respectively the National School Sports Olympiad. The aim is to educate all students in sports according to their skills, material basis, sports tradition of the educational unit, in order to lay the foundation for the creating the habit of systematic practice of some sports branches, namely the game of volleyball. Motor skills are absolutely necessary for a total participation of the student in all phases of attack and defense. Among these, the value of the motor quality, force, depends on the degree of training and applied efforts, efforts that must be large enough to lead to the development of the student’s moto qualities. Starting from the knowledge of morpho - functional peculiarities specific to the post-pubertal age, a pattern can be structured to identify the optimal solutions for the development of explosive force by general means but also specific to the game of volleyball. The efficiency and diversification strategies of stimulation and development of explosive force in volleyball play involve valuing the theoretical and practical knowledge and experience of the specialist, whose ultimate goal is to discover and capitalize the motor potential of high school students in order to achieve performance in school competitions.

The retreat of glaciers has led to increasing in natural hazards due, for example, by emptying of lakes dammed by unconsolidated glacial deposits (moraines) or ice, which are susceptible to catastrophic erosion, generating rapid floods, phenomena known as “Glacial Lake Outburst Floods” (GLOFs). Current systems that warn of the occurrence of a GLOF are activated when the emptying begins, which leaves little time to act, so they should be considered early alarm systems. The challenge is to predict the onset of the flood allowing the generation of an early warning system. To address this problem, SAGAZ ultimately aims to develop a system capable of identifying periods of increased GLOF risk using a predictive model fed by weather forecasts and monitoring station data. This system identifies a period of higher risk, which allows informing authorities several days in advance. This paper presents the results of the first phase of SAGAZ implementation, which aimed to (1) develop and validate a prototype monitoring station and deploy a network of stations on glacial lakes across southern Patagonia, (2) collect the necessary data for the development, training and validation of predictive models and (3) begin the implementation and testing of the predictive model. As a result, a network of 10 monitoring stations was installed in the Aysén and Magallanes regions of Chile and 1 in the Province of Santa Cruz in Argentina, of which 6 are currently operational and transmitting data in real time. The rest went off due to power failures and icebergs damaging sensors. The measures we have taken to avoid station’s failures are described, as well as some characteristics of the implemented prototype, the installed networks and the data obtained so far.

The living lab (LL) concept has a significant potential to drive sustainable development, particularly in the bioeconomy sector, by assisting communities in improving their quality of life whilst also considering the environmental impact. In this context, the main research question was the following: is there any specific mechanism through which living labs operate under the sustainable development concept? We reviewed 120 papers addressing this topic and performed a bibliometric analysis on the linkage between sustainability and living labs by applying the methodology of a systematic review. We concluded that living labs can drive innovation and experimentation in sustainability, which can be transposed into tangible solutions to economic, environmental, and social problems. The role of living labs in the transition to a bioeconomy is discussed and further research directions are presented.

Abstract Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss. Elevation of OXM, under basal and postprandial conditions, and similar metabolic adaptations after G49 treatment were found in plasma from patients with obesity early after metabolic bariatric surgery. These results identify G49 as a potential pharmacological alternative sharing with bariatric surgery hormonal and metabolic pathways.

Congenital cystic adenomatoid malformation encompasses a series of cystic malformative lesions characterized by aberrant bronchiolar formations of varying size and dispersion. Most cases of this illness are detected in the first few years of life, usually affecting infants. We report a case of CCAM presenting as pleural effusion in a 15-month-old boy who presented with acute respiratory distress. Chest CT revealed a cystic image in the right lower lobe of the lung. The patient had surgical excision, and a pathological examination validated the diagnosis of CCAM type 1 with no malignant material. Following surgery, the patient's general condition improved, and no new respiratory symptoms were observed during an 8-month follow-up period. Increased awareness of this rare condition among pediatricians and radiologists is crucial for facilitating early diagnosis and appropriate treatment.

Natives of the Low Rhine region, the Batavi were a community of ethnic soldiers engaged in a treaty with Rome, overseeing a heavy supply of men to the Roman auxiliary units. The present article examines the pottery discovered at and retrieved from three sites associated with Batavian auxilia: Războieni, Adony, and Romita. Their status as military sites shaped around the consumption habits of Batavian auxiliary troops makes them comparable. The comprehensive examination of pottery consumption patterns provides valuable insights into the dynamics of material culture in Dacia and Pannonia, facilitating our understanding of supply networks, consumption preferences, and cultural interactions within these frontier regions. The quantitative analyses of fabric and form distributions reveal distinctive trends at each site, reflecting variations in local production, regional trade networks, and social practices. The qualitative interpretations highlight the significance of certain vessel types and their cultural associations. While in the overall perspective, they emphasise the similarity between pottery consumption at the three forts shaped by military presence and regional trade networks, they also highlight potential markers of Batavian identity within the auxiliary units stationed there. By contextualising pottery within broader historical and archaeological frameworks, this research contributes to a more nuanced understanding of the cultural aspects of auxilia.

It is now generally accepted that the global order is shifting, but the literature is divided on how. Consequently, it is not surprising that there is a lack of strong scholarship on the characteristics of the order from a Central and Eastern European (CEE) perspective. Therefore, this article aims to explore the future of the Liberal World Order (LWO) from this perspective through the lens of mainstream theories. The article looks at the geopolitical dynamics of the region and the evolving strategic perceptions of the LWO. It examines how CEE, traditionally seen as the frontier of the LWO (EU and NATO), is navigating the complexities of the current global political landscape in the light of the changing order. The second part of the article specifically analyses the security perceptions of CEE governments. The article seeks to contribute to the understanding of the future trajectory of the LWO, the potential implications for global peace and security, and the interplay of realism and liberalism in shaping our understanding of this trajectory from the CEE perspective.

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In indoor environments, a structured strategy is needed to reduce the risk of infection. In addition to maintaining proper ventilation and wearing face masks, the development of effective technologies for limiting the transmission of SARS-CoV-2 through infectious respiratory particles (IRPs) has been studied. UV-C devices have already proved effective against other types of microorganisms and have also been investigated for their potential in inactivating SARS-CoV-2. This work aims to review and discuss these findings while also presenting recommendations for future research. Based on the available data, UV-C proved to be effective in the inactivation of airborne SARS-CoV-2 or its surrogates. The main gaps in this research have also been highlighted, and some outlooks for future studies have been suggested. In some studies, the use of surrogates with higher susceptibility to UV-C than airborne SARS-CoV-2 or the consideration of total bacterial counts alone may have led to misleading results. The question “how much variables affect the inactivation rate of airborne SARS-CoV-2 by UV-C in indoor environments?” is still unsolved, considering that the number of studies on the inactivation of this virus in real indoor environments is quite limited. The outcomes of this study can be useful for the scientific community, the technical stakeholders (e.g., managers in the healthcare and transport sectors), and the common people, providing important information about the performance of these technologies to improve the quality of air in indoor environments.

Background Digital therapeutics (DTx) are software-based interventions that aim to prevent or treat especially non-communicable diseases. Currently, no framework for reimbursement of DTx exists in Austria. The aim of this study was to gather a comprehensive perspective on regulatory considerations of Austrian stakeholders with regard to reimbursement of DTx and to outline strategies for establishing a national reimbursement framework. Methods Based on a stakeholder analysis, seven semi-structured interviews with Austrian experts from the digital health-related fields medicine, public health, health technology assessment, health industry and social security providers were conducted. Interviews were analyzed according to seven predefined themes. Results Overall, participants agreed that reimbursement of DTx by the public insurance in Austria is desirable. Prerequisites are (i) a high user and prescriber acceptance of DTx, which must be integrated into a transparent and interoperable Austrian e-Health infrastructure, (ii) a sufficient, risk-based level of evidence for clinical effectiveness, (iii) national authorities that transparently provide evidence-base, indications, contra-indications and potential risks, (iv) adopting European regulations about data security, secondary use of data and use of artificial intelligence and (v) a health-economical evaluation of DTx. Conclusion A comprehensive national strategy for reimbursing DTx will need to consider technical, scientific and socio-economical requirements, patient safety and liability, secure health data handling and use of artificial intelligence in order to establish a sound framework with equitable access also for socioeconomically disadvantaged persons in order to address the growing burden of non-communicable diseases.

Los estilos de liderazgo, en especial el transformacional, se indagan con frecuencia dado el impacto que tienen en otras variables organizacionales que resultan importantes para el alcance de resultados positivos dentro de las empresas. En este sentido, este estudio examina la relación entre el liderazgo transformacional, la cultura organizacional y su impacto en el desempeño laboral de los trabajadores civiles de una institución militar en Perú. Empleando un modelo de ecuaciones estructurales (PLS-SEM) y cuestionarios validados, se evaluaron cuatro dimensiones del liderazgo transformacional: Influencia idealizada, inspiración motivacional, estimulación intelectual y consideración individualizada, y cómo estas afectan la cultura organizacional y, en consecuencia, el desempeño laboral. Los resultados destacan que la dimensión "consideración individualizada" tiene una relación significativa y positiva con la cultura organizacional (0,867), y que esta cultura actúa como mediador entre el liderazgo y el desempeño laboral. No obstante, las demás dimensiones no mostraron una mediación significativa a través de la cultura organizacional. Estos hallazgos sugieren como conclusión que un enfoque de liderazgo orientado al apoyo individualizado y al fortalecimiento de la cultura organizacional puede optimizar el desempeño laboral, presentando implicaciones prácticas y teóricas relevantes en entornos organizacionales complejos.

El estrés académico es una preocupación significativa entre los estudiantes universitarios, afectando su bienestar emocional y rendimiento académico. La meditación mindfulness (MM) ha emergido como una intervención prometedora para mejorar las estrategias de afrontamiento al estrés. Este estudio tiene como objetivo evaluar la efectividad de un programa de meditación mindfulness de 12 semanas en mejorar las estrategias de afrontamiento al estrés académico en estudiantes de enfermería. Se utilizó un diseño experimental aleatorizado con 86 estudiantes de enfermería, asignados al grupo experimental (n=43) y al grupo control (n=43). El grupo experimental participó en un programa de MM basado en el protocolo MBSR durante 12 semanas, con sesiones semanales de 60 minutos y prácticas individuales diarias. Se midieron los niveles de mindfulness y las estrategias de afrontamiento al estrés antes y después de la intervención utilizando la Escala MAAS y la Escala de Estrategias de Afrontamiento A-CEA. Se realizaron análisis estadísticos mediante pruebas t y correlaciones de Pearson. Los resultados mostraron un incremento significativo en los niveles de mindfulness en el grupo experimental (M pre = 3.20, M post = 4.50; t (42) = -15.34, p < .001, d = 2.34), en comparación con el grupo control, que no presentó cambios significativos (p = .27). Además, se observaron mejoras significativas en las dimensiones de reevaluación positiva y planificación (p < .05) en el grupo experimental, mientras que la búsqueda de apoyo social mostró una tendencia al aumento sin alcanzar significancia estadística (p = .051). Este estudio sugiere que un programa de meditación mindfulness de 12 semanas es efectivo para mejorar ciertas estrategias de afrontamiento al estrés académico, específicamente la reevaluación positiva y la planificación. Estos hallazgos respaldan la incorporación de intervenciones de mindfulness en el currículo académico para promover el bienestar emocional y la gestión del estrés entre estudiantes universitarios.

Background: Coarctation of the aorta (CoA) is a relatively common congenital heart defect. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area. Methods: Tissue samples from 21 pediatric patients operated for CoA were dissected into separate biopsies consisting of the localized coarctation itself, proximal/distal tissue and ductus. RNA was sequenced to evaluate gene expression in the different biopsies. Results: We observed an activation of acute phase response in samples from the localized coarctation compared to samples from distal or proximal tissue. However, we observed even bigger differences for patient age and sex than compared to biopsy location. A cluster of genes located at 1q21, including the S100 gene family, displayed contrasting expression depending on patient sex, and appeared to affect the balance between inflammatory and interferon pathways. Biopsies from patients

Purpose To explore whether and how eHealth solutions support the dignity of healthcare professionals and patients in palliative care contexts. Method This qualitative study used phenomenographic analysis involving four focus group interviews, with healthcare professionals who provide palliative care to older people. Results Analysis revealed four categories of views on working with eHealth in hierarchical order: Safeguarding the patient by documenting—eHealth is a grain of support, Treated as less worthy by authorities—double standards, Distrust in the eHealth solution—when the “solution” presents a danger; and Patient first—personal contact with patients endows more dignity than eHealth. The ability to have up-to-date patient information was considered crucial when caring for vulnerable, dying patients. eHealth solutions were perceived as essential technological support, but also as unreliable, even dangerous, lacking patient information, with critical information potentially missing or overlooked. This caused distrust in eHealth, introduced unease at work, and challenged healthcare professionals’ identities, leading to embodied discomfort and feeling of a lack of dignity. Conclusion The healthcare professionals perceived work with eHealth solutions as challenging their sense of dignity, and therefore affecting their ability to provide dignified care for the patients. However, healthcare professionals managed to provide dignified palliative care by focusing on patient first.

Objectives: Protein kinase D (PKD) family is emerging as relevant regulator of metabolic homeostasis. However, the precise role of PKD2 in modulating hepatic insulin signaling has not been fully elucidated and it is the aim of this study. Methods: PKD inhibition was analyzed for insulin signaling in mouse and human hepatocytes. PKD2 was overexpressed in Huh7 hepatocytes and mouse liver, and insulin responses were evaluated. Mice with hepatocyte-specific PKD2 depletion (PKD2ΔHep) and PKD2fl/fl mice were fed a chow (CHD) or high fat diet (HFD) and glucose homeostasis and lipid metabolism were investigated. Results: PKD2 silencing enhanced insulin signaling in hepatocytes, an effect also found in primary hepatocytes from PKD2ΔHep mice. Conversely, a constitutively active PKD2 mutant reduced insulin-stimulated AKT phosphorylation. A more in-depth analysis revealed reduced IRS1 serine phosphorylation under basal conditions and increased IRS1 tyrosine phosphorylation in PKD2ΔHep primary hepatocytes upon insulin stimulation and, importantly PKD co-immunoprecipitates with IRS1. In vivo constitutively active PKD2 overexpression resulted in a moderate impairment of glucose homeostasis and reduced insulin signaling in the liver. On the contrary, HFD-fed PKD2ΔHep male mice displayed improved glucose and pyruvate tolerance, as well as higher peripheral insulin tolerance and enhanced hepatic insulin signaling compared to control PKD2fl/fl mice. Despite of a remodeling of hepatic lipid metabolism in HFD-fed PKD2ΔHep mice, similar steatosis grade was found in both genotypes. Conclusions: Results herein have unveiled an unknown role of PKD2 in the control of insulin signaling in the liver at the level of IRS1 and point PKD2 as a therapeutic target for hepatic insulin resistance.

What is this article about? A study (ClinicalTrials.gov identifier: NCT03583359) that tested whether an injectable filler treatment called calcium hydroxylapatite with lidocaine, or CaHA (+), could improve the shape of the jawline.How was the study in this summary conducted? Loss of jawline shape is a change to jawline appearance, like sagging or deflating, that occurs as people get older. A total of 123 participants received CaHA (+) injections on day 1 of the study (immediate treatment). Fifty-seven participants did not receive CaHA (+) until week 12 (delayed treatment). Jawline shape at week 12 was rated on a five-point scale (0 = no loss of shape or volume; 4 = extreme loss). Researchers also looked at participants’ satisfaction and self-reported improvement, ratings of how old participants thought they looked, and side effects.What were the results of the study? In the immediate treatment group, 76% of participants had improvement in jawline shape at week 12 (compared with 9% of participants in the delayed treatment group), which typically lasted approximately 8 months, and 94% self-reported improvement in jawline appearance. The participants were more satisfied with their jawlines and reported looking approximately 3 years younger at week 12 compared with before treatment. Regardless of sex or skin tone, side effects were categorized as mostly mild or moderate reactions, like lumps or bruising, at the site where CaHA (+) was injected.What do the results of this study mean? The results showed that CaHA (+) injections improved jawline shape in most participants and caused only mild or moderate side effects regardless of sex or skin tone, suggesting that CaHA (+) is safe and works well for diverse groups of patients.Who should read this article? This summary is for patients and others interested in learning about how CaHA (+) works, its safety, and its ability to improve jawline shape.Who sponsored this study? The study was sponsored by Merz North America, Inc.