Generation and characterization of three human induced pluripotent stem cell lines (EURACi007-A, EURACi008-A, EURACi009-A) from three different individuals of the same family with arrhythmogenic cardiomyopathy (ACM) carrying the plakophillin2 p.N346Lfs*12 mutation.

Abstract Arrhythmogenic Cardiomyopathy (ACM) is a genetically based cardiomyopathy associated with ventricular arrhythmias and fibro-fatty substitution of cardiac tissue. It is characterized by incomplete penetrance. We generated human iPSCs by episomal reprogramming of blood cells from three members of the same family: the proband, affected by ACM and carrying the heterozygous plakophillin2 p.N346Lfs*12 mutation, one asymptomatic carrier of the same mutation and one apparently healthy control. hiPSCs were characterized according to standard protocols including karyotyping, pluripotency marker expression and differentiation towards the three germ layers. These hiPSC lines can be used to study the mechanisms of ACM incomplete penetrance in vitro

Treatment Decision-Making of Secondary Prevention After Venous Thromboembolism: Data From the Real-Life START2-POST-VTE Register

Patients with venous thromboembolism (VTE) should receive a decision on the duration of anticoagulant treatment (AT) that is often not easy to make. Sixteen Italian clinical centers included patients with recent VTE in the START2-POST-VTE register and reported the decisions taken on duration of AT in each patient and the reasons for them. At the moment of this report, 472 (66.9%) of the 705 patients included in the registry were told to stop AT in 59.3% and to extend it in 40.7% of patients. Anticoagulant treatment lasted 653 months in >90% of patients and was extended in patients with proximal deep vein thrombosis because considered at high risk of recurrence or had thrombophilic abnormalities. d-dimer testing, assessment of residual thrombus, and patient preference were also indicated among the criteria influencing the decision. In conclusion, Italian doctors stuck to the minimum 3 months AT after VTE, while the secondary or unprovoked nature of the event was not seen as the prevalent factor influencing AT duration which instead was the result of a complex and multifactorial evaluation of each patient

Women Scientists Who Made Nuclear Astrophysics

Female role models reduce the impact on women of stereotype threat, i.e., of being at risk of conforming to a negative stereotype about one's social, gender, or racial group [1,2]. This can lead women scientists to underperform or to leave their scientific career because of negative stereotypes such as, not being as talented or as interested in science as men. Sadly, history rarely provides role models for women scientists; instead, it often renders these women invisible [3]. In response to this situation, we present a selection of twelve outstanding women who helped to develop nuclear astrophysics

Barriers and opportunities of soil knowledge to address soil challenges: Stakeholders? perspectives across Europe

Climate-smart sustainable management of agricultural soil is critical to improve soil health, enhance food and water security, contribute to climate change mitigation and adaptation, biodiversity preservation, and improve human health and wellbeing. The European Joint Programme for Soil (EJP SOIL) started in 2020 with the aim to significantly improve soil management knowledge and create a sustainable and integrated European soil research system. EJP SOIL involves more than 350 scientists across 24 Countries and has been addressing multiple aspects associated with soil management across different European agroecosystems. This study summarizes the key findings of stakeholder consultations conducted at the national level across 20 countries with the aim to identify important barriers and challenges currently affecting soil knowledge but also assess opportunities to overcome these obstacles. Our findings demonstrate that there is significant room for improvement in terms of knowledge production, dissemination and adoption. Among the most important barriers identified by consulted stakeholders are technical, political, social and economic obstacles, which strongly limit the development and full exploitation of the outcomes of soil research. The main soil challenge across consulted member states remains to improve soil organic matter and peat soil conservation while soil water storage capacity is a key challenge in Southern Europe. Findings from this study clearly suggest that going forward climate-smart sustainable soil management will benefit from (1) increases in research funding, (2) the maintenance and valorisation of long-term (field) ex-periments, (3) the creation of knowledge sharing networks and interlinked national and European in-frastructures, and (4) the development of regionally-tailored soil management strategies. All the above -mentioned interventions can contribute to the creation of healthy, resilient and sustainable soil ecosystems across Europe

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement

Multi-sectoral Impact Assessment of an Extreme African Dust Episode in the Eastern Mediterranean in March 2018

In late March 2018, a large part of the Eastern Mediterranean experienced an extraordinary episode of African dust, one of the most intense in recent years, here referred to as the “Minoan Red” event. The episode mainly affected the Greek island of Crete, where the highest aerosol concentrations over the past 15 yeas were recorded, although impacts were also felt well beyond this core area. Our study fills a gap in dust research by assessing the multi-sectoral impacts of sand and dust storms and their socioeconomic implications. Specifically, we provide a multi-sectoral impact assessment of Crete during the occurrence of this exceptional African dust event. During the day of the occurrence of the maximum dust concentration in Crete, i.e. March 22nd, 2018, we identified impacts on meteorological conditions, agriculture, transport, energy, society (including closing of schools and cancellation of social events), and emergency response systems. As a result, the event led to a 3-fold increase in daily emergency responses compare to previous days associated with urban emergencies and wildfires, a 3.5-fold increase in hospital visits and admissions for Chronic Obstructive Pulmonary Disease (COPD) exacerbations and dyspnoea, a reduction of visibility causing aircraft traffic disruptions (eleven cancellations and seven delays), and a reduction of solar energy production. We estimate the cost of direct and indirect effects of the dust episode, considering the most affected socio-economic sectors (e.g. civil protection, aviation, health and solar energy production), to be between 3.4 and 3.8 million EUR for Crete. Since such desert dust transport episodes are natural, meteorology-driven and thus to a large extent unavoidable, we argue that the efficiency of actions to mitigate dust impacts depends on the accuracy of operational dust forecasting and the implementation of relevant early warning systems for social awareness

Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

Multi-sectoral impact assessment of an extreme African dust episode in the Eastern Mediterranean in March 2018

In late March 2018, a large part of the Eastern Mediterranean experienced an extraordinary episode of African dust, one of the most intense in recent years, here referred to as the “Minoan Red” event. The episode mainly affected the Greek island of Crete, where the highest aerosol concentrations over the past 15 yeas were recorded, although impacts were also felt well beyond this core area. Our study fills a gap in dust research by assessing the multi-sectoral impacts of sand and dust storms and their socioeconomic implications. Specifically, we provide a multi-sectoral impact assessment of Crete during the occurrence of this exceptional African dust event. During the day of the occurrence of the maximum dust concentration in Crete, i.e. March 22nd, 2018, we identified impacts on meteorological conditions, agriculture, transport, energy, society (including closing of schools and cancellation of social events), and emergency response systems. As a result, the event led to a 3-fold increase in daily emergency responses compare to previous days associated with urban emergencies and wildfires, a 3.5-fold increase in hospital visits and admissions for Chronic Obstructive Pulmonary Disease (COPD) exacerbations and dyspnoea, a reduction of visibility causing aircraft traffic disruptions (eleven cancellations and seven delays), and a reduction of solar energy production. We estimate the cost of direct and indirect effects of the dust episode, considering the most affected socio-economic sectors (e.g. civil protection, aviation, health and solar energy production), to be between 3.4 and 3.8 million EUR for Crete. Since such desert dust transport episodes are natural, meteorology-driven and thus to a large extent unavoidable, we argue that the efficiency of actions to mitigate dust impacts depends on the accuracy of operational dust forecasting and the implementation of relevant early warning systems for social awareness.Thanks are due to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020+UIDB/50017/2020) through national funds, and also to the Icelandic Research Fund for the grant no. 207057-051. Authors S. Kazadzis and P. Kosmopoulos would like to acknowledge the European Commission project EuroGEO e-shape (grant agreement No 820852). Also, International Cooperative for Aerosol Prediction (ICAP) and NASA mission researchers are gratefully for providing aerosol data for this study. Aurelio Tobias was supported by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S). S. Kutuzov acknowledges the Megagrant project (agreement No. 075-15-2021-599, 8.06.2021)

INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study.

OBJECTIVES: To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project. DESIGN: Population-based cohort study, the INTERGROWTH-21st Project. SETTING: Brazil, India, Italy, Kenya and the UK. PARTICIPANTS: 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes. PRIMARY MEASURES: Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones. RESULTS: Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA's cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA's negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22-30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges. CONCLUSIONS: From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes