Search Results (78)

Oil-in-water emulsions (O/W emulsions) are generally used to lubricate the cold rolling process of low-carbon steel. In addition to the obvious advantages of efficient lubrication and cooling of the process, there are also some disadvantages, mainly related to emulsion bath maintenance, subsequent production steps and waste disposal. In some application areas, Oil-Free Lubricants (OFL’s) have been shown to be at least equally effective in decreasing friction and wear as conventional oil-based lubricants, while resulting in benefits related to waste disposal. In 2023, a project named “Transfer of aqueous oil free lubricants into steel cold rolling practice” (acronym ‘RollOilFreeII’) began, with it receiving funding from the Research Fund for Coal and Steel (RFCS). This project aims at an industrial application of Oil-Free Lubricants in the steel cold rolling process. The project builds on the work of the ‘RollOilFree’ project (also carried out in the RFCS-framework). This article briefly recapitulates the findings in the RollOilFree project and describes the objectives, benefits, activities and first results of the RollOilFreeII project. Notably, a pilot mill trial at high speed has been carried out, showing a good performance of the investigated OFLs. Back-calculated friction values were equal to, or even slightly lower than, reference O/W emulsions. The strip cleanliness with OFLs is much better than it is with the reference O/W emulsions. Only for a very thin product, as is the case in tinplate rolling, does the direct application of a conventional O/W dispersion (a high-particle-sized O/W emulsion) give a better performance than the investigated OFLs. Further development of OFLs should focus on this aspect. Full article

The integration of renewable energy sources (RESs) and the establishment of energy communities (ECs) are vital steps in achieving global sustainability goals. This paper presents a methodology for developing and validating a Smart Grid Architecture Model (SGAM)-compliant software platform designed to integrate data-driven energy services and connect physical energy assets within energy communities. The platform aims to optimize energy dispatch, enhance self-consumption, and facilitate interoperability with smart grid infrastructures. Two case studies—Polígono Industrial Las Cabezas in Spain and the IMP R&D campus in Serbia—are analyzed to highlight real-world challenges, solutions, and lessons learned. The article points to different scenarios relevant for energy community design and implementation. Lessons learned point to challenges related to device integration, production forecasting, user engagement, and regulatory barriers. The results show that the proposed SGAM platform successfully addresses technical and operational complexities, supporting energy efficiency, decarbonization, and scalability. Full article

Highly pathogenic avian influenza (HPAI) epizootics have caused repeated mass mortality events among wild birds. The effect of the infection is potentially detrimental for a variety of bird species, including the Peregrine Falcon (Falco peregrinus). The numbers of wintering and breeding Peregrine Falcons in the Netherlands have recently declined. We investigated the changes in population trends in relation to HPAI H5 virus outbreaks. For this purpose, we analyzed variations in annual numbers of wintering and breeding birds, the virology of reported dead birds, and the presence of the HPAI H5 virus in unhatched eggs. We showed that significant mortalities of Peregrine Falcons had occurred in 2016–2017 and 2020–2023, years of major HPAI H5 virus outbreaks. In particular, the highest rates of bird mortality and HPAI virus infection were reported in 2023. In this year, over 80% (28/32) of the tested birds were positive for HPAI H5 virus. No HPAI H5 virus was present in the eggs. Based on these findings, we concluded that HPAI represents a serious threat to the Peregrine Falcon population in the Netherlands, and, in combination with anthropogenic factors, may contribute to the decline of this species. Targeted HPAI surveillance and disease mitigation measures are necessary for the conservation of this species. Full article

Water resource management in agriculture faces complex challenges due to increasing scarcity, exacerbated by climate change, and the intensification of conflicts among various user groups. This study addresses the issue of predicting and managing these conflicts in the Longaví River Basin, Chile, by considering the intricate interactions between hydrological, social, and economic factors. A socio-hydrological agent-based model (SHABM) was developed, integrating hydrological, economic, and behavioral data. The methodology combined fieldwork with computational modeling, characterizing three types of agents (selfish, neutral, and cooperative) and simulating scenarios with varying levels of water availability and oversight across three water user organizations (WUOs). The key findings revealed that (1) selfish agents are more likely to disregard irrigation schedules under conditions of scarcity and low supervision; (2) high supervision (90%) significantly reduces conflicts; (3) water scarcity exacerbates non-cooperative behaviors; (4) high-risk conflict areas can be identified; and (5) behavioral patterns stabilize after the third year of simulation. This work demonstrates the potential of SHABM as a decision-making tool in water management, enabling the proactive identification of conflict-prone areas and the evaluation of management strategies. Full article

Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of Lal knockout (Lal KO) mice. Both models develop progressive lymphocyte dysfunction and expansion of myeloid-derived suppressor (CD11b+ Gr-1+) cells. To study whether MMP-12 might be a detrimental contributor to the pathology of LAL-D, we have generated Lal/Mmp12 double knockout (DKO) mice. The phenotype of Lal/Mmp12 DKO mice closely resembled that of Lal KO mice, while the weight and morphology of the thymus were improved in Lal/Mmp12 DKO mice. Cytological examination of blood smears showed a mildly reversed lymphoid-to-myeloid shift in DKO mice. Despite significant decreases in CD11b+ Ly6G+ cells in the peripheral blood, bone marrow, and spleen of Lal/Mmp12 DKO mice, the hematopoietic bone marrow progenitor compartment and markers for neutrophil chemotaxis were unchanged. Since the overall severity of LAL-D remains unaffected by the deletion of Mmp12, we conclude that MMP-12 does not represent a viable target for treating the inflammatory pathology in LAL-D. Full article

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations. Full article

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint. Full article

The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement (BC) in medium- and high-viscosity versions were compared to unloaded BC using a vacuum mixing system. As an additional control group, manual mixed unloaded BC was used. In a uniaxial compression test, ultimate compressive strength, compressive yield strength, and compression modulus of elasticity, as well as ultimate and yield strain, were determined according to ISO 5833-2022 guidelines. All groups exceeded the minimum compressive strength (70 MPa) specified in the ISO 5833 guidelines. Both ALBC groups showed a similar ultimate compressive and yield strength to the unloaded BC. The results showed that vacuum mixing increased the compression strength of BC. ALBC showed similar compressive strength to their non-antibiotic counterparts when vacuum mixing was performed. Added low-dose gentamicin acted as a plasticizer on bone cement. From a biomechanical point of view, the usage of gentamicin-based ALBC formulations is viable. Full article

Background: Clinical reasoning (CR) is fundamental in medical education. However, the Italian curriculum has not incorporated a structured CR format yet. Therefore, we introduced the Clinical Case Discussions (CCD), to medical students attending the University of Bologna as a tool for developing CR abilities. CCDs are a case-based peer-teaching format, simulating the diagnostic process using published patient cases. Methods: Students of all clinical years of the University of Bologna Medical School were invited to voluntarily participate in a two-day CCD training program. They completed pre- and post-training questionnaires assessing their expectations before and impressions after the training and comparing learning outcomes to their usual classes. Results: Twenty-one students participated in this pilot program. Before the training, more than half of the participants expressed either interest or a strong interest in all proposed learning objectives. Afterward, 84.6% of the students stated that the training much exceeded (63.5%) or exceeded (23.1%) their expectations considering its utility for their future medical activities. A total of 92.3% strongly agreed (84.6%) or agreed (7.7%) to have improved their CR. Conclusions: Although this pilot program had some intrinsic limitations, the students’ positive feedback on this CCD format (combining the benefits of case-based learning and peer teaching) encourages further research on its potential role in the Italian curriculum. Full article

The International One Health Conference 2023, scheduled for October in Barcelona, fosters a collaborative, multidisciplinary approach to health involving professionals, academics, and decision-makers. Operating in a hybrid format, the conference aims to bridge the gap between scientific knowledge and policies, aligning with the Sustainable Development Goals (SDGs) and Health in All Policies (HiAP). Emphasizing community involvement and the symbiotic relationship between basic needs, sustainable lifestyles, and empowerment, the conference envisions a comprehensive approach to sustainable development. D’Alisa introduces a framework incorporating participative democracy, recognizing the interconnectedness of economic, social, environmental, and participative democratic dimensions. Framing questions for the conference delve into critical aspects, addressing the integration of the One Health framework within health sectors, emphasizing interlinkages between health, climate change, and decision-making. The conference’s five-dimension framework tackles the complexity of One Health, addressing concerns, solutions, and opportunities in a holistic paradigm. Full article

High-grade gliomas (HGGs) and glioblastoma multiforme (GBM) are characterized by a heterogeneous and aggressive population of tissue-infiltrating cells that promote both destructive tissue remodeling and aberrant vascularization of the brain. The formation of defective and permeable blood vessels and microchannels and destructive tissue remodeling prevent efficient vascular delivery of pharmacological agents to tumor cells and are the significant reason why therapeutic chemotherapy and immunotherapy intervention are primarily ineffective. Vessel-forming endothelial cells and microchannel-forming glial cells that recapitulate vascular mimicry have both infiltration and destructive remodeling tissue capacities. The transmembrane protein TMEM230 (C20orf30) is a master regulator of infiltration, sprouting of endothelial cells, and microchannel formation of glial and phagocytic cells. A high level of TMEM230 expression was identified in patients with HGG, GBM, and U87-MG cells. In this study, we identified candidate genes and molecular pathways that support that aberrantly elevated levels of TMEM230 play an important role in regulating genes associated with the initial stages of cell infiltration and blood vessel and microchannel (also referred to as tumor microtubule) formation in the progression from low-grade to high-grade gliomas. As TMEM230 regulates infiltration, vascularization, and tissue destruction capacities of diverse cell types in the brain, TMEM230 is a promising cancer target for heterogeneous HGG tumors. Full article

Background: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. Methods: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, “combined”). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013–2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. Results: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)—better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). Conclusions: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans. Full article

The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis. Full article

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM. Full article

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in the elderly and in children, associated with pediatric hospitalizations. Recently, first vaccines have been approved for people over 60 years of age applied by intramuscular injection. However, a vaccination route via mucosal application holds great potential in the protection against respiratory pathogens like RSV. Mucosal vaccines induce local immune responses, resulting in a fast and efficient elimination of respiratory viruses after natural infection. Therefore, a low-energy electron irradiated RSV (LEEI-RSV) formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) was tested ex vivo in precision cut lung slices (PCLSs) for adverse effects. The immunogenicity and protective efficacy in vivo were analyzed in an RSV challenge model after intranasal vaccination using a homologous prime-boost immunization regimen. No side effects of PC-LEEI-RSV in PCLS and an efficient antibody induction in vivo could be observed. In contrast to unformulated LEEI-RSV, the mucosal vaccination of mice with PC formulated LEEI-RSV showed a statistically significant reduction in viral load after challenge. These results are a proof-of-principle for the use of LEEI-inactivated viruses formulated with liposomes to be administered intranasally to induce a mucosal immunity that could also be adapted for other respiratory viruses. Full article