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Energy security has become a pressing issue in the European Union (EU), particularly due to geopolitical turbulence and supply chain disruptions. The continuous crises and the recent Russian invasion of Ukraine have highlighted the vulnerabilities of EU nations that rely on external energy sources, exposing them to potential price fluctuations and supply constraints. The aim of this study is to systematically review the EU’s international economic relations through the prism of energy security. The review presents two topics of discussion that have been prevalent in the last decade: (i) the EU’s economic and energy relations with other countries and (ii) the types of energy that are being traded. The review reaches the conclusion that the EU must reduce its reliance on Russian fossil fuels by developing new alliances and focusing on renewable energy sources.

Background: Adenoviral vector COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is a heparin-independent platelet-activating disorder. An increasing number of VITT-like disorders without previous vaccination are being identified. Key Clinical Question: To explore the association of the pediatric cluster of postinfectious thrombosis and thrombocytopenia with VITT-like disorders. Clinical Approach: Three children with severe thrombocytopenia, coagulopathy, elevated D-dimer, and thrombotic events (cerebral venous sinus thrombosis) were reported. Two had positive nasopharyngeal samples for adenovirus, and 1 had group A streptococcus infection. They all had a COVID-19 history and low-risk antiphospholipid syndrome. Heterozygosity for factor V Leiden was found in 2 children. In 2 patients for whom anti–platelet factor 4 (PF4) serology was performed, positive results were found by PF4/polyanion lateral-flow immunoassay but negative results by PF4/polyanion chemiluminescence immunoassay. All patients were treated with enoxaparin or fondaparinux and intravenous immunoglobulin, while 3 received platelets transfusion and steroids. Conclusion: This cluster of pediatric cases with thrombosis and thrombocytopenia may indicate a postinfectious (most notably, postadenovirus) VITT-like disorder.

BackgroundProgrammed cell death 1 receptor (PD-1) inhibition as monotherapy followed by Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibition in case of progression or as upfront double co-inhibition has drastically improved the survival outcomes of metastatic melanoma. Still, many patients develop primary or acquired resistance to both agents, relapse soon, and survive less. For these patients, the therapeutic options are very limited, and for many years, conventional chemotherapy (CC) was the standard of care. Recently, the phase II LEAP-004 trial supported that pembrolizumab/lenvatinib could potentially overcome anti-PD-1/anti-CTLA-4 immunotherapy refractoriness.Materials and methodsIn the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m2 i.v. Q3W) in melanoma patients who relapsed to both checkpoint inhibitors, either in combinatorial or in sequential setting, between July 2022 and January 2024. Baseline demographics, disease characteristics, and treatment outcomes (objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)) were recorded. Survival analyses were performed using the Kaplan–Meier method. All patients were also considered for safety analysis.ResultsA total of 84 patients were included in the effectiveness and safety analysis (pembrolizumab/lenvatinib, n=39 and CC, n=45). The median age was 67 (45–87) years and 64 (34–87) years, and men were 33.3% and 46.7%, respectively. The distribution of their metastatic sites was comparable, including 12.8% and 20% with brain involvement. Most patients had a good PS

Otoliths are important structures for balance and hearing of fish and constitute a useful tool in fisheries science. This study provides, for the first time in the Mediterranean, information on the otolith morphometrics of Dentex maroccanus, collected from the South Aegean Sea, and enriches the existing information on its age and growth by sex. The otolith shape variables examined showed a more circular to square otolith shape, related to the body size. Significant differences between sexes were detected for the otolith Area, Diameter, Perimeter, and Radius. Exponential regressions were used to examine the relationship of the otolith variables with total body length, from which five showed a strong correlation (Diameter, Width, Radius, Area, and Perimeter). The eviscerated weight–length relationship exhibited an isometric growth for both sexes, whereas when total weight was applied, a positive allometric growth was found for females. Sagittal otolith readings revealed four age groups for females and five for males. A Bhattacharya method was used for age validation. Von Bertalanffy growth parameters were as follows: L∞ = 23.08, k = 0.27, t0 = −1.93 for females and L∞ = 24.07, k = 0.24, t0 = −2.26 for males. This research offers valuable biological information for Dentex maroccanus useful in fisheries science.

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p < 0.0001) and MM (p < 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

Introduction: Wearable Activity Trackers (WATs) offer real-time feedback on activity levels. We assessed the impact of WAT usage on physicians’ exercise habits. Methods: Physicians from the Athens Medical Association, Greece (n = 742) responded to a self-administered questionnaire evaluating usage of WAT, demographic characteristics, specialty, and physical exercise habits. WHO guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in Users of WATs (Group A), and Non-Users of WATs (Group B). This is an observational, cross-sectional study. Results: There was no difference in baseline characteristics between the two groups (age, sex, body mass index). WATs were used by 38%. Between Group A and B, there was difference in mean exercise training time (302 ± 304 min vs. 210 ± 268 min, p < 0.001), higher percentage of WHO goal achievement (66.3% vs. 50.7%, p < 0.001), and greater awareness of WHO Guidelines (59.9% vs. 47.4%, p < 0.001). WATs were mostly used by four main specialties, with higher use from Cardiologists: Cardiology (47%), Endocrinology (44%), Surgery (35%) and Internal Medicine (25%), with a p = 0.045. Finally, users of WATs compared to non-users showed higher willingness to reduce body weight (58.5% vs. 48%, p = 0.01), apply dietary restrictions (36.5% vs. 29.6%, p = 0.05), and greater motivation for weekly physical exercise (74.1% vs. 32.4%, p < 0.001); Conclusion: Physicians using WATs demonstrate increased exercise training time, greater awareness of WHO guidelines and a higher propensity to implement dietary restrictions compared to non-users. Variations in WAT usage across medical specialties emphasize the need for targeted interventions to promote physical activity and enhance healthcare professionals’ health.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

IntroductionArticulography and functional neuroimaging are two major tools for studying the neurobiology of speech production. Until now, however, it has generally not been feasible to use both in the same experimental setup because of technical incompatibilities between the two methodologies.MethodsHere we describe results from a novel articulography system dubbed Magneto-articulography for the Assessment of Speech Kinematics (MASK), which is technically compatible with magnetoencephalography (MEG) brain scanning systems. In the present paper we describe our methodological and analytic approach for extracting brain motor activities related to key kinematic and coordination event parameters derived from time-registered MASK tracking measurements. Data were collected from 10 healthy adults with tracking coils on the tongue, lips, and jaw. Analyses targeted the gestural landmarks of reiterated utterances/ipa/ and /api/, produced at normal and faster rates.ResultsThe results show that (1) Speech sensorimotor cortex can be reliably located in peri-rolandic regions of the left hemisphere; (2) mu (8–12 Hz) and beta band (13–30 Hz) neuromotor oscillations are present in the speech signals and contain information structures that are independent of those present in higher-frequency bands; and (3) hypotheses concerning the information content of speech motor rhythms can be systematically evaluated with multivariate pattern analytic techniques.DiscussionThese results show that MASK provides the capability, for deriving subject-specific articulatory parameters, based on well-established and robust motor control parameters, in the same experimental setup as the MEG brain recordings and in temporal and spatial co-register with the brain data. The analytic approach described here provides new capabilities for testing hypotheses concerning the types of kinematic information that are encoded and processed within specific components of the speech neuromotor system.

Hydrogen offers a route to storing renewable electricity and lowering greenhouse gas emissions. Metal–organic framework (MOF) adsorbents are promising candidates for hydrogen storage, but a deep understanding of their potential for large-scale, stationary back-up power applications has been lacking. Here we utilize techno-economic analysis and process modelling, which leverage molecular simulation and experimental results, to evaluate the future opportunities of MOF-stored hydrogen for back-up power applications and set critical targets for future material development. We show that with carefully designed charging–discharging patterns, MOFs coupled with electrolysers and fuel cells are economically comparable with contemporary incumbent energy-storage technologies in back-up power applications. Future research should target developing MOFs with 15 g kg−1 of recoverable hydrogen adsorbed (excess uptake) and could be manufactured for under US$10 kg−1 to make the on-site storage system a leading option for back-up power applications.

In the framework of our studies on Citrus cultivars in Greece, the chemical composition of the essential oils (EOs) from the peels and leaves of orange, pummelo, and tangelo (mandarin × grapefruit hybrid) cultivated in Greece have been studied. All EOs have been analyzed through GC-MS, and a total of 47 and 87 metabolites were identified in the peels and leaves, respectively. These metabolites are classified into the chemical groups of terpenes, alcohols, aldehydes, esters, ketones, and organic acids. Limonene was the most abundant compound in the peel EOs. Moreover, bioactive polymethoxyflavones (PMFs) were isolated and structurally determined from the peels of orange and tangelo, highlighting them as a good potential source of natural PMFs. All EOs were evaluated for their antimicrobial activity against nine human pathogenic microorganisms (six bacteria and three fungi), showing an interesting profile. The EOs from the peels of all Citrus species exhibited a stronger antimicrobial activity compared to those from the leaves. The susceptibility of the assayed Gram-positive bacteria was observed to be greater than that of Gram-negative bacteria, while the fungi were also relatively less resistant than bacteria. The rootstock choice did not influence the EO profile of the fruit peel but exerted an influence on the chemical profile of the leaves.

The onset of the COVID-19 pandemic prompted a rapid shift to Emergency Remote Teaching (ERT). Social networks had a key role in supporting the educational community in facing challenges and opportunities. A quantitative study was conducted to assess the Greek teachers’ perceptions of social network support. Findings indicated that teachers turned to universities, educational institutions, the Ministry of Education, school support groups, and virtual communities for support. Additionally, the study revealed the barriers faced by teachers, including infrastructure limitations, technical difficulties, skill deficiencies, problems with students’ engagement, and school policies. Teachers’ evaluation of support regarding ERT provided fruitful insight. The results illustrate teachers’ perspectives on ERT, contributing to the ongoing discourse on educational resilience to unpredictable disruptions. In conclusion, the role of social networks was considered as critical for the teachers to overcome barriers during ERT with the formation of social communities for support and the sharing of common experiences. Expertise in internet use and social networking played a significant role in readiness for the abrupt shift to distance education. The present study uniquely contributes to the educational field by emphasizing the role of teachers’ support as an innovative approach to holistically enhance teachers’ performance in ERT.

Using deep archival observations from the Chandra X-ray Observatory, we present an analysis of linear X-ray-emitting features located within the southern portion of the Galactic center chimney and oriented orthogonal to the Galactic plane, centered at coordinates l = 0.°08, b = −1.°42. The surface brightness and hardness ratio patterns are suggestive of a cylindrical morphology, which may have been produced by a plasma outflow channel extending from the Galactic center. Our fits of the feature’s spectra favor a complex two-component model consisting of thermal and recombining plasma components, possibly a sign of shock compression or heating of the interstellar medium by outflowing material. Assuming a recombining plasma scenario, we further estimate the cooling timescale of this plasma to be on the order of a few hundred to thousands of years, leading us to speculate that a sequence of accretion events onto the Galactic black hole may be a plausible quasi-continuous energy source to sustain the observed morphology.

Numerous adsorption-based technologies are emerging as candidates for hydrogen transportation, and yet little is known about their practical viability. As such, new approaches are needed to conduct early validation of emerging hydrogen transportation concepts despite a lack of clear criteria for viable future hydrogen supply chains. In this work, we conduct technoeconomic modeling to quantify cost, performance, and relations between system components for early-stage adsorbent-based hydrogen supply chains. We compare results with the cost and performance of high pressure compressed gas and liquid hydrogen trucks in the same applications. Using available experimental adsorption data, we simulate the gravimetric performance of tube trailer trucks packed with metal-organic frameworks (MOFs) operated at 100 bar and 77 or 200 K. We also extrapolated available experimental data to study a third scenario where tube trailer trucks are operated at ambient temperature and 250 bar. Models developed for these conditions represent feasible operation scenarios where pressurization or cooling costs can be reduced relative to compressed or liquid hydrogen truck systems. Results suggest that the levelized cost of long-distance transmission, including a gas terminal and MOF-based truck fleet, ranges from $7.3 to $29.0 per kg H2. The levelized cost of transmission using compressed hydrogen gas trucks at 350 and 500 bar and liquid hydrogen trucks is substantially lower, at $1.8, $1.7 and $3.1 per kg H2, respectively. In a short-distance urban distribution application, the MOF-based truck fleet, gas terminal, and refueling stations have a levelized cost between $11.8 and $40.0 per kg H2, which is also more expensive than distribution in the case of the 350 bar, 500 bar and liquid hydrogen trucks, which have levelized costs of $4.7, $4.1 and $3.9 per kg H2, respectively. Key opportunities identified for lowering costs are: increasing the hydrogen capacity of the tube system by developing new MOFs with higher volumetric deliverable capacities, flexible allowable daily deliveries per refueling station, increasing the cycling stability of the MOF, and driverless trucks.

This study aims to optimize the frying process of natural porous materials (like potatoes) by enhancing heat and mass transfer phenomena through significant horizontal acceleration values following a spatially periodic pattern that alternates the intensity of inertia forces uniformly across the frying vessel. The generated horizontal inertial forces act complementary to the normal vertical buoyancy force for the creation of agitating convective currents in the oil and for vapor bubbles’ departure from the surface of frying objects. The use of an innovative frying device, employing simultaneous rotation around two vertical axes at a different speed in a so-called planetary type of motion, serves to facilitate this production of horizontal acceleration values that allows intensifying the performance of frying. The present investigation examines the impact of rotational speed, along with oil temperature and frying duration, on the water loss and sensory evaluation of fried items. The potato-to-oil ratios typically found in industrial frying operations are employed. The intended outcome is a more energy-efficient frying process, reduced cooking times, and a healthier product due to lower frying temperatures and the consequent decreased formation of harmful compounds. This approach carries substantial implications for food processing, potentially enhancing productivity while limiting operational costs.

Trachinus draco and Trachinus radiatus are two bycatch species of low commercial value and no sufficient knowledge on their biological features. In the present study, the weight–length relationship, age, growth, and ten otolith morphometric variables of these species were investigated in the southwestern Aegean Sea for the first time. Positive allometric and isometric growth in the weight were defined in T. draco and T. radiatus. The weight–length relationship was described by the parameters α = 0.002415 and b = 3.35745 in T. draco and α = 0.007582 and b = 3.09452 in T. radiatus. The von Bertalanffy growth function parameters were L∞ = 44.51 cm, k = 0.15 year−1, and t0 = −1.31 years for T. draco and L∞ = 58.47 cm, k = 0.16 year−1, and t0 = −0.78 years for T. radiatus. Ten otolith variables (radius, length, width, area, perimeter, roundness, circularity, form factor, rectangularity, and ellipticity) showed a significant relationship with size for both species, except the ellipticity in T. radiatus. The mean values of all the otolith variables were higher in T. radiatus than in T. draco. The otolith of T. radiatus was found to become more rectangular with size as compared to the otolith of T. radiatus. The results of this work can support further research on the behavioral and ecological features of the two species.

Gaseous streams in biorefineries have been undervalued and underutilized. In cellulosic biorefineries, coproduced biogas is assumed to be combusted alongside lignin to generate process heat and electricity. Biogas can instead be upgraded to compressed biomethane and used as a transportation fuel. Capturing CO2-rich streams generated in biorefineries can also contribute to greenhouse gas (GHG) mitigation goals. We explore the economic and life-cycle GHG impacts of biogas upgrading and CO2 capture and storage (CCS) at ionic liquid-based cellulosic ethanol biorefineries using biomass sorghum. Without policy incentives, biorefineries with biogas upgrading systems can achieve a comparable minimum ethanol selling price (MESP) and reduced GHG footprint ($1.38/liter gasoline equivalent (LGE) and 12.9 gCO2e/MJ) relative to facilities that combust biogas onsite ($1.34/LGE and 24.3 gCO2e/MJ). Incorporating renewable identification number (RIN) values advantages facilities that upgrade biogas relative to other options (MESP of $0.72/LGE). Incorporating CCS increases the MESP but dramatically decreases the GHG footprint (-21.3 gCO2e/MJ for partial, -110.7 gCO2e/MJ for full CCS). The addition of CCS also decreases the cost of carbon mitigation to as low as $52-$78/t CO2, depending on the assumed fuel selling price, and is the lowest-cost option if both RIN and California's Low Carbon Fuel Standard credits are incorporated.

Timetables for energy transition vary across EU Member States. The planning for dealing with the consequences of the transition in affected regions also varies. Under the pressure of the ten-year economic crisis, Greece is one of the few countries that has committed to stop using lignite in electricity generation, achieving 80% by 2023 and definitively by 2028. Apart from its environmental impact, the country assessed using lignite in electricity generation as unprofitable and damaging to the Greek economy. Simultaneously, it formulated a national energy transition plan for the country’s lignite areas. The plan also provides support for existing enterprises and incentives for new enterprises. European and domestic financial instruments accompany the support incentives. The compressed timetable is ambitious and demanding, entailing risks of project failure. As one of the first Member State projects to be completed in 2028, its outcome will shape an ambient atmosphere, positive or negative, for other Member States’ projects as well. Based on the transition plan and the timelines to which Greece has committed, this research examines the reanimation of rural areas involved in lignite mining from the perspective of entrepreneurship and financial support instruments. The findings revealed that while there is strong social consensus around the design that incorporates best practices, the basis for the completion schedule has unrealistic elements that will have potentially negative consequences for the restoration of the areas that the energy transition affects. The present study highlights the risks for entrepreneurship that tight schedules pose in the context of lignite area redevelopment.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Background: Checkpoint inhibitor (CPI)-associated diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE) that presents with variable clinical manifestations. Data about its pathogenesis have not yet been adequately studied. Methods: Applying the recently updated diagnostic criteria from the American Diabetes Association, we retrospectively reviewed the medical records of all CPI-treated patients referred to our endocrinological unit for managing their endocrine irAEs and analyzed the incidence of CPI-DM, its clinical characteristics, and its management. Results: Among the 326 CPI-treated patients with endocrine irAEs, 4 patients met the updated criteria for the diagnosis of CPI-DM, representing 1.22% of all endocrine irAEs in our cohort. These four patients presented with distinct clinical scenarios regarding the irAE onset, the underlying malignancy, the administered CPI regimen, and the type of circulating autoantibodies. Conclusion: The variable presentation of CPI-DM and the non-standard sensitivity of the presence of the type 1 DM traditional autoantibodies highlight the need for distinct guidelines and increased awareness of its diagnosis and management.

Immune checkpoints (ICs) are molecules implicated in the fine-tuning of immune response via co-inhibitory or co-stimulatory signals, and serve to secure minimized host damage. Targeting ICs with various therapeutic modalities, including checkpoint inhibitors/monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and CAR-T cells has produced remarkable results, especially in immunogenic tumors, setting a paradigm shift in cancer therapeutics through the incorporation of these IC-targeted treatments. However, the large proportion of subjects who experience primary or secondary resistance to available IC-targeted options necessitates further advancements that render immunotherapy beneficial for a larger patient pool with longer duration of response. B7-H3 (B7 Homolog 3 Protein, CD276) is a member of the B7 family of IC proteins that exerts pleiotropic immunomodulatory effects both in physiologic and pathologic contexts. Mounting evidence has demonstrated an aberrant expression of B7-H3 in various solid malignancies, including tumors less sensitive to current immunotherapeutic options, and has associated its expression with advanced disease, worse patient survival and impaired response to IC-based regimens. Anti-B7-H3 agents, including novel mAbs, bispecific antibodies, ADCs, CAR-T cells, and radioimmunotherapy agents, have exhibited encouraging antitumor activity in preclinical models and have recently entered clinical testing for several cancer types. In the present review, we concisely present the functional implications of B7-H3 and discuss the latest evidence regarding its prognostic significance and therapeutic potential in solid malignancies, with emphasis on anti-B7-H3 modalities that are currently evaluated in clinical trial settings. Better understanding of B7-H3 intricate interactions in the tumor microenvironment will expand the oncological utility of anti-B7-H3 agents and further shape their role in cancer therapeutics.

Summary: Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Energy security has become a pressing issue in the European Union (EU), particularly due to geopolitical turbulence and supply chain disruptions. The continuous crises and the recent Russian invasion of Ukraine have highlighted the vulnerabilities of EU nations that rely on external energy sources, exposing them to potential price fluctuations and supply constraints. The aim of this study is to systematically review the EU's international economic relations through the prism of energy security. The review presents two topics of discussion that have been prevalent in the last decade: (i) the EU's economic and energy relations with other countries and (ii) the types of energy that are being traded. The review reaches the conclusion that the EU must reduce its reliance on Russian fossil fuels by developing new alliances and focusing on renewable energy sources. [ABSTRACT FROM AUTHOR]

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p < 0.0001) and MM (p < 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death 1 receptor (PD-1) inhibition as monotherapy followed by Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibition in case of progression or as upfront double co-inhibition has drastically improved the survival outcomes of metastatic melanoma. Still, many patients develop primary or acquired resistance to both agents, relapse soon, and survive less. For these patients, the therapeutic options are very limited, and for many years, conventional chemotherapy (CC) was the standard of care. Recently, the phase II LEAP-004 trial supported that pembrolizumab/lenvatinib could potentially overcome anti-PD-1/anti-CTLA-4 immunotherapy refractoriness. Materials and methods: In the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m2 i.v. Q3W) in melanoma patients who relapsed to both checkpoint inhibitors, either in combinatorial or in sequential setting, between July 2022 and January 2024. Baseline demographics, disease characteristics, and treatment outcomes (objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)) were recorded. Survival analyses were performed using the Kaplan-Meier method. All patients were also considered for safety analysis. Results: A total of 84 patients were included in the effectiveness and safety analysis (pembrolizumab/lenvatinib, n=39 and CC, n=45). The median age was 67 (45-87) years and 64 (34-87) years, and men were 33.3% and 46.7%, respectively. The distribution of their metastatic sites was comparable, including 12.8% and 20% with brain involvement. Most patients had a good PS<2 (69.9% and 56.5%), increased lactate dehydrogenase (LDH) (71.8% and 84.4%), BRAF-wild status (82.1% and 84.8%), and received ≥2 previous systemic therapies (61.5% and 53.3%). The median follow-up was 18 months. The ORR was 23.1% and 11.1% (p<0.0001), the median PFS was 4.8 months and 3.8 months [HR (95%CI), 0.57 (0.36-0.92); p=0.017], and the median OS was 14.2 months and 7.8 months [HR (95%CI), 0.39 (0.22-0.69), p=0.0009] in pembrolizumab/lenvatinib and CC arms, respectively. Grade 3-5 treatment-related adverse events were documented in 48.7% (pembrolizumab/lenvatinib) and 75.6% (CC) of patients (p=0.034), which led to treatment discontinuation in 10.3% and 17.8% of cases, respectively. Conclusions: This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly longer outcomes in cases treated with pembrolizumab/lenvatinib versus CC. [ABSTRACT FROM AUTHOR]

European hake, Merluccius merluccius L. 1758, is a highly valuable demersal fish species exploited in both the east Atlantic and the Mediterranean Sea. Changes in the size-at-maturity of this species have been reported in various geographic areas. Size-at-maturity is a key parameter in fishery management. Our main goal was to study the trend of the size-at-maturity of European hake in the eastern Ionian Sea (Central Mediterranean) over the last five decades. Utilizing a multi-decadal series of data for various environmental variables, we employed multivariate analyses and non-additive modeling in an attempt to identify shifts in the climatic environment of the eastern Ionian Sea and whether the maturation of the hake population could be affected by these changes. The analyses used suggest a plausible environmental regime shift in the study area in the late 1990s/early 2000s. The decrease in size-at-maturity that was detected in the last two decades may, thus, be associated with environmental changes. However, as many fish stocks already experience fishery-induced evolution, further investigation is necessary to determine whether this environmental effect is an additional stressor on a possibly already fishery-impacted population. The outcomes of this study highlight the importance of investigating the relationship between fish reproductive traits and altered environmental conditions, as the latter are generally ignored during assessments, affecting the robustness of fishery management.

Background: Relationships among perinatal depression occurring a number of weeks before and after childbirth and smoking have been identified. Depression may lead to the inability to abstain from smoking during pregnancy. Objectives: This study aims to determine factors affecting smoking during pregnancy revealing potential relationships between depression and smoking patterns during and after pregnancy. Methods: A total of 206 mothers participated in the study. Data were collected through self-reporting as respondents were asked to answer questionnaires during the 12th week of pregnancy, during the 30th week of pregnancy, after childbirth, and during the period after pregnancy. Relationships between smoking behavior, sociodemographic variables, and feelings of perinatal depression were examined using chi-square test and binary logistic regression analysis. A follow-up investigation has been conducted after 2 years revealing the percentage of women returning to their smoking habits. Results: Smokers before (B?=?0.568; p?=?0.026) and during pregnancy (B?=?1.238; p?=?0.009) were more likely to express depression before childbirth. Average daily cigarette consumption before (B?=?1.110; p?=?0.001) and during pregnancy (B?=?1.167; p?=?0.002) was associated with depression during pregnancy. Women who smoked during pregnancy reported significantly more depressive symptoms after pregnancy (B?=?1.757; p?=?0.005) compared with nonsmokers and smokers who abstained during pregnancy. Average daily cigarette consumption during pregnancy (B?=?1.402; p?=?0.002) affects the expression of depression after pregnancy. Women who smoked before pregnancy (B?=?0.568; p?=?0.025) and their average daily cigarette consumption before pregnancy (B?=?1.465; p?=?0.025) were highly associated with the inability to abstain from smoking during pregnancy. However, the knowledge of risks of maternal smoking during pregnancy (B?=??1.110; p?=?0.001) and medical consult on abstaining (B?=??1.238; p?=?0.009) reinforced the maternal attempt to quit smoking. The follow-up investigation revealed an elevated amount of women returning to previous smoking patterns. Discussion: Perinatal depression is associated with smoking patterns during pregnancy. Assessment of depression and smoking is needed throughout perinatal period to support the health of women.

Patients with sickle cell disease (SCD) suffer from complications due to anemia, inflammation, and vaso-occlusion. Factors that trigger sickling and/or inflammation may initiate such complications, while treatment with hydroxyurea (HU) reduces their emergence and prolongs survival. On the contrary, inhibition of the BRAF-MEK-ERK pathway with BRAF and MEK inhibitors (BRAF/MEKi) has revolutionized treatment of melanoma but their use has been correlated with inflammatory adverse events. Thus, treatment of patients with SCD with BRAF/MEKi may be quite challenging and pyrexia in those patients should be managed as a medical emergency. In this article, intrigued by the case of a 36-year-old female patient with S/β-thal under HU who was treated with dabrafenib and trametinib for melanoma, we analyze the mechanisms underlying inflammation and vaso-occlusion in SCD, the mechanisms of pyrexia and inflammation induced by BRAF/MEKi, their potential interconnections, the shared role of the inflammasome in these two entities, and the protective effect of HU in SCD. Since SCD is the most common inheritable blood disorder, the administration of BRAF/MEKi for melanoma in patients with SCD may be a rather common challenge. Thus, proper treatment with HU may pave the way for an uneventful management of such patients.

AimMarathon is a running event in which athletes must cover a distance of 42.195 km. In addition to participating in marathons, marathoners have incorporated extensive running into their lifestyle. In the present study, we investigated the effect of long-term strenuous exercise in the form of marathon running on the immune system.Methods & ResultsWe collected peripheral blood samples from 37 male marathoners before/after a race and 37 age/sex/body mass index (BMI)-matched healthy sedentary controls. Hematological and biochemical tests revealed race-induced leukocytosis attributable to neutrophilia and significant increases in plasma lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and cortisol concentrations. Phenotypic analysis of lymphocytes revealed race-induced significant decrease in the number of lymphocytes, memory helper T (Th) cells, naive, memory and activated cytotoxic T (Tc) cells, natural killer (NK), NKT, and B1 cells, and a significant increase in the number of activated Th and regulatory Th cells (Tregs). Compared with controls, marathoners maintained significantly lower levels of memory and activated Th cells and higher levels of activated Tc and B1 cells. Measurement of plasma cytokine levels revealed a pro-inflammatory cytokine polarization that increased after the race. Examination of gene expression of cytokines and Th-cell signature transcription factors in peripheral blood mononuclear cells revealed a significant decrease in tumor necrosis factor α (TNF-α) and interleukin (IL)-17, and a significant increase in IL-6, IL-10 and forkhead box P3 (FoxP3) after the race. Compared with controls, marathoners maintained significantly higher levels of TNF-α. Assessment of the suppressive capacity of Tregs in co-cultures of isolated effector Th cells and Tregs showed significantly increased suppressive capacity of marathoners’ Tregs after the race.ConclusionsCompared with controls, marathoners live with permanent changes in certain immune parameters. Marathoners exhibit a stable pro-inflammatory cytokine polarization that increases after the race and is counterbalanced by increased numbers of Tregs overexpressing FoxP3 and having increased suppressive capacity.