Angiopoietins as Predictor Indexes in COVID-19 Patients in Delta and Omicron Waves.

This study aimed to explore the correlation between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 Coronavirus Disease 2019 (COVID-19) adult patients, 30 hospitalized intensive care units (ICU), 30 inward units (non-ICU), and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU-ICU groups) for the Ang-1 and Ang-2 indices. The Ang-2/Ang-1 ratio has differed significantly among the individual patient groups. An ROC analysis was conducted to find an optimal threshold for distinguishing between (outpatients-non-ICU) and (non-ICU-ICU) groups. It was based on Youden's index of 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analyzed as severity indicators in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated better prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies to improve outcomes.

IgIDivA: immunoglobulin intraclonal diversification analysis.

Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio.tools/igidiva.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction.

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARß, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-ß was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from E. coli, followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies.

A Survey on Quantitative Risk Estimation Approaches for Secure and Usable User Authentication on Smartphones.

Mobile user authentication acts as the first line of defense, establishing confidence in the claimed identity of a mobile user, which it typically does as a precondition to allowing access to resources in a mobile device. NIST states that password schemes and/or biometrics comprise the most conventional user authentication mechanisms for mobile devices. Nevertheless, recent studies point out that nowadays password-based user authentication is imposing several limitations in terms of security and usability; thus, it is no longer considered secure and convenient for the mobile users. These limitations stress the need for the development and implementation of more secure and usable user authentication methods. Alternatively, biometric-based user authentication has gained attention as a promising solution for enhancing mobile security without sacrificing usability. This category encompasses methods that utilize human physical traits (physiological biometrics) or unconscious behaviors (behavioral biometrics). In particular, risk-based continuous user authentication, relying on behavioral biometrics, appears to have the potential to increase the reliability of authentication without sacrificing usability. In this context, we firstly present fundamentals on risk-based continuous user authentication, relying on behavioral biometrics on mobile devices. Additionally, we present an extensive overview of existing quantitative risk estimation approaches (QREA) found in the literature. We do so not only for risk-based user authentication on mobile devices, but also for other security applications such as user authentication in web/cloud services, intrusion detection systems, etc., that could be possibly adopted in risk-based continuous user authentication solutions for smartphones. The target of this study is to provide a foundation for organizing research efforts toward the design and development of proper quantitative risk estimation approaches for the development of risk-based continuous user authentication solutions for smartphones. The reviewed quantitative risk estimation approaches have been divided into the following five main categories: (i) probabilistic approaches, (ii) machine learning-based approaches, (iii) fuzzy logic models, (iv) non-graph-based models, and (v) Monte Carlo simulation models. Our main findings are summarized in the table in the end of the manuscript.

The Dynamic and Crucial Role of the Arginine Methylproteome in Myoblast Cell Differentiation.

Protein arginine methylation is an extensive and functionally significant post-translational modification. However, little is known about its role in differentiation at the systems level. Using stable isotope labeling by amino acids in cell culture (SILAC) proteomics of whole proteome analysis in proliferating or five-day differentiated mouse C2C12 myoblasts, followed by high-resolution mass spectrometry, biochemical assays, and specific immunoprecipitation of mono- or dimethylated arginine peptides, we identified several protein families that were differentially methylated on arginine. Our study is the first to reveal global changes in the arginine mono- or dimethylation of proteins in proliferating myoblasts and differentiated myocytes and to identify enriched protein domains and novel short linear motifs (SLiMs). Our data may be crucial for dissecting the links between differentiation and cancer growth.

Investigating nurses' knowledge and attitudes about delirium in older persons: a cross-sectional study.

INTRODUCTION: Delirium is the most common emergency for older hospitalized patients that demands urgent treatment, otherwise it can lead to more severe health conditions. Nurses play a crucial part in diagnosing delirium and their competencies facilitate the appropriate treatment and management of the condition. AIM: This study aims to enhance the understanding of delirium care by exploring both knowledge and attitudes of nurses toward patients in acute care hospital wards and the possible association between these two variables. METHOD: The Nurses Knowledge of Delirium Questionnaire (NKD) and the Attitude Tool of Delirium (ATOD) that were created for the said inquiry, were disseminated to 835 nurses in the four largest Public Hospitals of the Republic. These tools focused particularly on departments with increased frequency of delirium (response rate = 67%). RESULTS: Overall nurses have limited knowledge of acute confusion/delirium. The average of correct answers was 42.2%. Only 38% of the participants reported a correct definition of delirium, 41.6 correctly reported the tools to identify delirium and 42.5 answered correctly on the factors leading to delirium development. The results of the attitudes' questionnaire confirmed that attitudes towards patients with delirium may not be supportive enough. A correlation between the level of nurses' knowledge and their attitude was also found. The main factors influencing the level of knowledge and attitudes were gender, education, and workplace. CONCLUSION: The findings of this study are useful for the international audience since they can be used to develop and modify educational programmes in order to rectify the knowledge deficits and uninformed attitudes towards patients with delirium. The development of a valid and reliable instrument for the evaluation of attitudes will help to further assess nurses' attitudes. Furthermore, the results are even more important and useful on a national level since there is no prior data on the subject area, making this study the first of its kind.

International validation of the EORTC QLQ-CLL17 questionnaire for assessment of health-related quality of life for patients with chronic lymphocytic leukaemia.

Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient-reported health-related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ-CLL17 to supplement the core questionnaire (EORTC QLQ-C30). Patients with CLL (n = 341) from 12 countries completed the QLQ-C30, QLQ-CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%-66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test-retest and convergent validity was demonstrated. The QLQ-CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1-3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ-CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision-making.

Self-regulatory processes in early childhood as predictors of Hispanic children's BMI z-scores during the elementary school years: Differences by acculturation and gender.

Over the last decade, longitudinal research has shown that children's general, top-down self-regulation during early childhood is negatively associated with children's weight status in elementary school. The samples in these previous studies have been primarily White, and no study to date has examined this issue in a sample of Hispanic children from low-income families-a population at high risk for childhood obesity. The present study followed 130 Hispanic children over a time period of three to just under five years, examining the degree to which multiple measures of general, top-down self-regulation, along with a measure of appetite regulation (eating in the absence of hunger), predicted children's BMI z-scores in the early elementary school years. Results showed that children's ability to delay gratification in the preschool years was negatively associated with later BMI z-scores and that children's eating in the absence of hunger was positively associated. In separate models by gender, these relationships were significant only for girls. Moreover, analyses run separately for children of mothers low or high on acculturation showed that the relationship between delay of gratification and later BMI z-scores was significant only for children whose mothers were low on acculturation. Possible socialization and environmental factors contributing to these findings are considered.

Blockchain-Based Security Mechanisms for IoMT Edge Networks in IoMT-Based Healthcare Monitoring Systems.

Despite the significant benefits that the rise of Internet of Medical Things (IoMT) can bring into citizens' quality of life by enabling IoMT-based healthcare monitoring systems, there is an urgent need for novel security mechanisms to address the pressing security challenges of IoMT edge networks in an effective and efficient manner before they gain the trust of all involved stakeholders and reach their full potential in the market of next generation IoMT-based healthcare monitoring systems. In this context, blockchain technology has been foreseen by the industry and research community as a disruptive technology that can be integrated into novel security solutions for IoMT edge networks, as it can play a significant role in securing IoMT devices and resisting unauthorized access during data transmission (i.e., tamper-proof transmission of medical data). However, despite the fact that several blockchain-based security mechanisms have already been proposed in the literature for different types of IoT edge networks, there is a lack of blockchain-based security mechanisms for IoMT edge networks, and thus more effort is required to be put on the design and development of security mechanisms relying on blockchain technology for such networks. Towards this direction, the first step is the comprehensive understanding of the following two types of blockchain-based security mechanisms: (a) the very few existing ones specifically designed for IoMT edge networks, and (b) those designed for other types of IoT networks but could be possibly adopted in IoMT edge networks due to similar capabilities and technical characteristics. Therefore, in this paper, we review the state-of-the-art of the above two types of blockchain-based security mechanisms in order to provide a foundation for organizing research efforts towards the design and development of reliable blockchain-based countermeasures, addressing the pressing security challenges of IoMT edge networks in an effective and efficient manner.

The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes.

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP.

BACKGROUND: R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. MATERIALS AND METHODS: We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R-CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. RESULTS: With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%-27% of patients [pts]) with approximately 19%-23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. CONCLUSION: The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. IMPLICATIONS FOR PRACTICE: By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Maternal feeding style and child weight status among Hispanic families with low-income levels: a longitudinal study of the direction of effects.

BACKGROUND: The home environment is a central and modifiable influence on the development of childhood obesity. Evidence supports the central role of parents in shaping problematic child eating behaviors and excess weight. Most studies of feeding emphasize parent-driven influences without taking into account the child's role in eating interactions. Few studies have addressed the bi-directional nature of feeding dynamics in studies of young children. METHODS: The goals of this study were: 1) to examine if parental feeding styles during preschool (4-5 years) predict child weight status at 7-9 years, and 2) to examine the direction of effects between parental feeding styles and child weight status over time. Participants were part of a larger longitudinal study of Hispanic Head Start families living in the West South Central United States. Data from mother/child dyads were collected at three time points: Time 1 (ages 4-5), Time 2 (ages 5 ½-6 ½), and at Time 3 (ages 7-9). Only data from the Times 1 and 3 were used in the current analyses. A total of 128 mothers and their children had data on all variables needed for the analyses. Assessments included parent-reported feeding styles, feeding practices, acculturation, child eating behaviors, and child height and weight. Hierarchical regression was used to examine the first aim; a cross-lagged panel analysis examined the second aim. RESULTS: An indulgent parental feeding style at ages 4-5 was associated with increased child BMI z-score at ages 7-9. Indulgent feeding significantly contributed to child BMI z-score beyond demographics, baseline child BMI z-score, parental acculturation, and child eating behaviors. Regarding the direction of effects in parental feeding interactions, the cross-lagged analyses showed that both indulgent feeding style and authoritative feeding style at Time 1 positively predicted child BMI z-scores at Time 3. Child effects were significant as well. Child BMI z-score at Time 1 positively predicted indulgent feeding and negatively predicted authoritarian feeding at Time 3. CONCLUSIONS: Indulgent feeding should be addressed in future family-focused childhood obesity initiatives focused on young children and their parents.

Prothrombin complex concentrate in major bleeding associated with DOACs; an updated systematic review and meta-analysis.

BACKGROUND: Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review. METHODS: We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence. RESULTS: 33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75-0.84), mortality (15%, CI 0.11-0.19) and thromboembolic adverse events (3%, CI 0.02-0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13-0.32). Heterogeneity was significant (Ι2 > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled. CONCLUSION: Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.

Generating Datasets for Anomaly-Based Intrusion Detection Systems in IoT and Industrial IoT Networks.

Over the past few years, we have witnessed the emergence of Internet of Things (IoT) and Industrial IoT networks that bring significant benefits to citizens, society, and industry. However, their heterogeneous and resource-constrained nature makes them vulnerable to a wide range of threats. Therefore, there is an urgent need for novel security mechanisms such as accurate and efficient anomaly-based intrusion detection systems (AIDSs) to be developed before these networks reach their full potential. Nevertheless, there is a lack of up-to-date, representative, and well-structured IoT/IIoT-specific datasets which are publicly available and constitute benchmark datasets for training and evaluating machine learning models used in AIDSs for IoT/IIoT networks. Contribution to filling this research gap is the main target of our recent research work and thus, we focus on the generation of new labelled IoT/IIoT-specific datasets by utilising the Cooja simulator. To the best of our knowledge, this is the first time that the Cooja simulator is used, in a systematic way, to generate comprehensive IoT/IIoT datasets. In this paper, we present the approach that we followed to generate an initial set of benign and malicious IoT/IIoT datasets. The generated IIoT-specific information was captured from the Contiki plugin "powertrace" and the Cooja tool "Radio messages".

Total Annual Economic Burden of Patients with Sickle Cell Disease in Steady State in Greece.

Sickle cell disease includes a group of congenital hemolytic anemias, all characterized by the predominance of Hb S (HBB: c.20A>T). The population movement due to economic migration or escape from conflict zones will further affect the health systems of countries by either increasing the number of patients or forcing countries to create care units for sickle cell disease patients. This will probably also increase the incidence of the disease in areas where their incidence and prevalence were previously low. In the present study, an attempt has been made to estimate the total annual cost of the treatment of sickle cell disease in Greece. This was the first attempt to calculate the total annual cost of treating sickle cell disease patients in a steady state. The annual cost of sickle cell disease was estimated to be €21,152,340.00 (US$25,219,300.41), without calculating the cost of hospitalization for severe complications. Since 2013, in Greece, a pharmaceutical expenditure limit (decreasing with the years) has been budgeted at €1,945,000,000.00 (US$2,318,965,150.00), annually. It is therefore calculated that approximately 1.0% of the budget allocated to pharmaceutical spending is used to treat patients with sickle cell disease.

West Nile neuroinvasive disease. Report of four cases in Northern Greece, 2018.

West Nile virus (WNV) is a mosquito-borne RNA flavivirus which caused several epidemics worldwide. The year 2018 was a WNV record year for Europe, including Greece, with earlier and longer transmission season with higher than the previous number of cases. It has been proposed that some simple biochemical markers may be helpful for the recognition of WNV neuroinvasive disease, its differential from other neurological infectious diseases and prognosis. We describe four cases that suffered from WNV meningitis and/or encephalitis hospitalized in 2018 in a tertiary hospital in Thessaloniki, Greece, and investigate the importance of simple biomarkers for the recognition of WNV etiology.

Estimated glomerular filtration rate independently predicts outcome of azacitidine therapy in higher-risk Myelodysplastic syndromes. Results from 536 patients of the Hellenic National Registry of Myelodysplastic and Hypoplastic syndromes.

Higher-risk Myelodysplastic syndromes (MDS) patients undergoing treatment with 5-azacytidine (AZA) are typically elderly with several comorbidities. However, the effect of comorbidities on the effectiveness and safety of AZA in real-world settings remains unclear. We analyzed data from 536 AZA-treated patients with higher-risk MDS, Myelodysplastic/Myeloproliferative neoplasms and low blast count Acute Myeloid Leukemia enrolled to the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes. Multivariate analysis adjusted also for the International Prognostic Scoring System (IPSS), its revised version (IPSS-R) and the French Prognostic Scoring System (FPSS), demonstrated independent associations of overall and leukemia-free survival with estimated glomerular filtration rate (eGFR) <45 mL min-1 /1.73 m2 (P = .039, P = .023, respectively), ECOG performance status <2 (P = .015, P = .006), and presence of peripheral blood blasts (P = .008, P = .034), while secondary MDS also correlated with significantly shorter leukemia-free survival (P = .039). Addition of eGFR <45 mL min-1 /1.73 m2 , in IPSS-R and FPSS increased the predictive power of both models. Only FPSS ≤2 and eGFR <45 mL min-1 /1.73 m2 predicted worse response to AZA in multivariate analysis, whereas eGFR <45 mL min-1 /1.73 m2 correlated significantly with death from hemorrhage (P = .003) and cardiovascular complications (P = .006). In conclusion, in the second largest real-world series of AZA-treated MDS patients, we show that an eGFR <45 mL min-1 /1.73 m2 is an independent predictor of worse response and survival. This higher cut-off, instead of the commonly used serum creatinine >2 mg/dL, can be utilized as a more precise indicator of renal comorbidity during AZA therapy. Incorporation of eGFR in the prognostic assessment of AZA-treated MDS patients may prove useful not only in routine practice, but also for the appropriate patient stratification in clinical trials with AZA combinations.