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Government-led repurposing programmes are reshaping the division of labour in pharmaceutical innovation. A new power drafted into the European Union pharmaceutical reform package will allow the European Medicines Agency (EMA) to add new therapeutic indications to marketed medicines without the marketing authorization holder's consent. Companies oppose this power, but in weighing up enacting the power, society has a poor understanding of its potential to help patients. This study offers the first empirical assessment of the promise of the power. It analyses 198 medicines from 12 years, comparing EMA-authorized labels with those authorized by the US Food and Drug Administration and a leading reference for off-label uses. Sixty-seven per cent of the medicines have at least one additional use supported by clinical evidence, yielding 320 potential new uses. Of these, 39 per cent are for new diseases and 61 per cent for new patient cohorts, a third of the latter concerning paediatric populations. Commentators generally omit discussing repurposing for new patient cohorts, even though it is a focus of the European Commission. The study's results suggest that the power could be used to authorize a meaningful number of evidence-based uses, especially those already authorized in the USA, while also revealing a policy synergy for neglected populations.

The rising prevalence of illicit drug use among Romanian youth underscores the need for effective prevention service delivery systems, particularly in European contexts characterized by high social transition, severe resource constraints, and limited prevention service infrastructure. This study explored international expert and local Romanian stakeholder perspectives regarding factors contributing to the contextual adaptation and potential implementation of the Communities That Care (CTC) prevention system in Romania. Through qualitative interviews with experts in CTC (n = 15) and validation of findings with Romanian community stakeholders (n = 9), this study examined potential challenges in implementing CTC in Romania, such as lack of evidence-based interventions, resource scarcity, cultural differences, and resistance to change. Key factors identified by CTC experts as needed for successful implementation include community improved readiness, continuous adaptation, favorable facilitator and champion characteristics, and community engagement. Romanian stakeholder perspectives further suggested that rural communities may offer particularly favorable conditions for CTC implementation. Stakeholders emphasized the need for partnerships that reflect the needs of local groups and for attention to Romanian values (e.g., including strong family ties, religious traditions, and respect for authority), which should be considered alongside broader societal experiences (e.g., migration, funding limitations, and long-standing institutional distrust). By situating Romania within a broader European context, these findings provide valuable insights for stakeholders seeking to adapt and implement CTC in countries new to the prevention science movement and highlight the relevance of the Romanian case for the Balkan region and similar European settings.

Cutibacterium acnes (C. acnes) is the most common pathogen in shoulder periprosthetic joint infection (PJI) but remains difficult to distinguish from contamination due to its low virulence and presence as a skin commensal. Diagnostic ambiguity and variable antibiotic resistance further complicate management. We analyzed 87 C. acnes isolates from patients undergoing evaluation for shoulder PJI across two institutions. Isolates were obtained from intraoperative cultures and stored for subsequent analysis. Hemolysis, aerotolerance, and growth rate were assessed in vitro. Antimicrobial susceptibility to five antibiotics was determined using minimum inhibitory concentration (MIC) testing, with interpretive breakpoints defined by both the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Infection status was classified per the 2018 International Consensus Meeting (ICM) criteria into definite, probable, possible, or unlikely categories. Associations between phenotypic traits and infection classification were assessed using univariate and multivariable statistical models. Only 12.6% (n = 11) of cases met criteria for definite infection, while the majority (48.3%) were classified as probable. Hemolysis and aerotolerance were observed in 51.7% and 54.0% of isolates, respectively, and were strongly associated with one another (P < .001); however, neither phenotype was associated with infection classification in univariate or multivariable analysis. Clindamycin resistance was observed in a minority of isolates but varied by standard, with 12.6% classified as resistant by EUCAST and 6.9% as non-susceptible by CLSI. No isolates were resistant to vancomycin; doxycycline and rifampin MICs were uniformly low. Neither hemolysis nor aerotolerance reliably distinguished definite PJI from non-definite cases, limiting their diagnostic utility in this cohort. Clindamycin resistance was uncommon, yet classification differed based on the interpretive criteria used (CLSI vs. EUCAST), highlighting potential inconsistencies in clinical reporting. Moreover, the predominance of "probable" infections illustrates a critical limitation of current consensus criteria, which may both underestimate true infection burden in indolent presentations and overestimate infection due to reliance on positive cultures in the absence of clear clinical findings. More precise diagnostic frameworks may help address current classification challenges and better support clinical decision-making in shoulder arthroplasty.

Novel invasive genotypes can arise through polyploidisation, hybridisation, or gene flow between populations of distinct origins or related species. Solidago gigantea, a notorious European invader, has long been reported exclusively as tetraploid in its invasive range. Recently, mixed-ploidy populations, including tetraploid and pentaploid plants, were discovered; yet the potential role of the novel pentaploid cytotype (and its progeny) in S. gigantea invasions remains poorly understood. This study aims to elucidate the origin of pentaploids and the cytotype and genetic structure of mixed-ploidy populations, characterise the reproductive mode and mating interactions of pentaploid plants, and assess their fitness and potential contribution to invasiveness using relative DNA content screening, ddRADseq population genetics, and reproductive potential and fitness assessments. Molecular analyses revealed that pentaploids constitute a genetically distinct lineage within S. gigantea. Our results rule out both an autopolyploid origin from the common tetraploid cytotype and an allopolyploid origin via hybridisation with co-occurring native or invasive Solidago species. The pentaploid cytotype reproduces exclusively through clonal propagation; its low genetic variability suggests that the two studied populations may belong to a single extensive clonal genet. Pentaploids produce viable gametes but appear to exhibit strict self-incompatibility, preventing the formation of offspring within the same genotype. However, pentaploid S. gigantea engages in bidirectional mating with co-occurring tetraploid plants, yielding well-developed seeds with offspring ploidy ranging from 4x to 5x (predominantly aneuploid). Despite this cytological variability, progeny from mixed-ploidy populations displayed germination rates and early growth comparable to those from pure tetraploid populations. Notably, at least some tetraploid offspring from 4x-5x crosses successfully established, flowered, and backcrossed with pentaploid plants to produce viable seeds of subsequent introgressed generations. The pentaploid cytotype of S. gigantea introduces a new post-invasion dynamic to its invasive populations. Rather than being an evolutionary dead-end, this cytotype may potentially enhance the species' invasiveness through three evolutionary pathways: (1) a highly successful clonal life strategy enabling both local and long-distance spread; (2) genetic enrichment of tetraploid populations via ongoing interploidy crosses; and (3) establishment of novel aneuploid genotypes due to the remarkable tolerance of chromosomal instability observed in S. gigantea.

Specialized transport systems are used for newborns who require medical care. These complex systems are subjected to vehicle-specific vibration and sound during transport. Prolonged exposure to high levels of sound and vibration can be harmful to humans. This study aimed to quantify the sound and vibration levels experienced within a fixed-wing aircraft (Pilatus PC-12) during neonatal transport. A dedicated flight test was performed in a PC-12. Acceleration and sound data were captured in the cabin at the approximate position of the neonatal patient transport system, were it loaded. Resultant motions of the transport system and patient were estimated using experimentally derived transfer functions. Vertical vibration was most significant, and the average motion of the cabin floor and pilot seat was comparable in the 1 to 80 Hz frequency range. The greatest motion occurred during segments of rough turbulence, when patient levels were estimated to reach the ISO 2631 "very uncomfortable" threshold. Sound levels exceeded the 60 dBA limit recommended by the CSA Group and the European Committee for Standardization across all phases of flight, peaking at 89.3 dBA during a short-field landing. Measured cabin sound exceeded recommended limits, and vertical accelerations reached levels considered uncomfortable under ISO 2631, highlighting the potential risk to this physiologically vulnerable population, compelling further research into vibration mitigation strategies. Aircraft acceleration data have enabled more extensive laboratory testing of the transport system. Establishing neonatal-specific whole-body vibration guidelines remains essential to fully understand and address the clinical implications of these exposures.

A successful green biodiesel process was achieved through the full utilization of catalysts derived from waste. The catalysts in this study were composed of nano CaO (31.0&#x202f;nm, calcined eggshell undergoing hydration-dehydration cycles) and MgAlOx mixed oxides (14.0&#x202f;nm, derived from Mg-Al layered double hydroxide). Transesterification of waste cooking oil using only CaO resulted in 95.9&#x202f;&#xb1;&#x202f;0.8% biodiesel. Using a combination of CaO and MgAlOx in a mass ratio of 70:30 achieved an improved biodiesel yield of 97.8&#x202f;&#xb1;&#x202f;0.5% under optimal conditions (molar ratio of methanol to oil at 12:1, catalyst mass fraction of 3&#x202f;wt%, temperature of 60&#x202f;&#xb0;C, duration of 45&#x202f;min, and ultrasonic support). The recycled CaO/MgAlOx hybrid catalyst exhibits greater stability compared to pure CaO, achieving 91.4&#x202f;&#xb1;&#x202f;1.2% of its initial activity after five reuse cycles for the mixed catalyst, whereas pure CaO attains only 87.9&#x202f;&#xb1;&#x202f;1.5%. Feedstocks with elevated Free Fatty Acid (FFA) content can be transformed into biodiesel using the hybrid catalyst, yielding 96.9&#x202f;&#xb1;&#x202f;0.7% from waste cow fat. All produced biodiesels meet American Society for Testing and Materials (ASTM) D6751 and European Committee for Standardization (EN) 14,214 standards. All biodiesel-diesel blends with varying biodiesel ratios- B5 (5%), B10 (10%), and B20 (20%) meet ASTM D7467 standards; therefore, the biodiesel can be used in existing diesel engines. This demonstrates a circular economy approach where various waste products can be recycled into high-value biodiesel using sustainable catalysts under green conditions.

To compare the effects of single antiplatelet (SAPT), dual antiplatelet (DAPT), and anticoagulation plus antiplatelet (AC&#x2009;+&#x2009;AP) therapies on branch vessel patency and bleeding risk after branched endovascular aortic repair (B-EVAR). This single-center retrospective cohort study included 250 patients with 880 target branches who underwent B-EVAR (2015-2025). Primary outcomes were branch patency loss (occlusion/stenosis requiring reintervention) and major bleeding (ISTH criteria). Propensity score weighting and competing risk regression controlled confounding. During median 18-month follow-up, 82 branches (9.3%) lost patency: 12.0% (SAPT), 7.0% (DAPT), 7.5% (AC&#x2009;+&#x2009;AP). DAPT significantly improved patency vs. SAPT (sHR 0.72, p&#x2009;=&#x2009;0.045). Major bleeding occurred in 22 patients (8.8%): 4.4% (SAPT), 7.5% (DAPT), 22.5% (AC&#x2009;+&#x2009;AP). AC&#x2009;+&#x2009;AP tripled bleeding risk (HR 3.10, p&#x2009;=&#x2009;0.001); DAPT showed non-significant trend (HR 1.62, p&#x2009;=&#x2009;0.13). DAPT provided the most favorable balance between branch vessel patency and major bleeding after B-EVAR. AC&#x2009;+&#x2009;AP was associated with substantially higher bleeding and should be reserved for patients with an independent indication for anticoagulation. Taken together with prior multicenter European and US consortium data, these findings support a class IB-level preference for DAPT in patients without competing anticoagulation needs; prospective randomized multicenter trials are needed to support a class IA recommendation.

Allexiviruses (family Alphaflexiviridae) are widespread pathogens of vegetatively propagated allium crops, but their occurrence has not previously been documented in Ukraine. We surveyed cultivated allium plants collected in eight Ukrainian regions (2022-2025) and screened their samples for garlic virus B (GarV-B), garlic virus C (GarV-C) and shallot virus X (ShVX) using enzyme-linked immunosorbent assay (ELISA). GarV-B, GarV-C and ShVX were detected in 39/108 (36.1%), 23/108 (21.3%) and 21/108 (19.4%) plants, respectively, with infections which were strongly host-associated: garlic (n&#x2009;=&#x2009;63) had high frequencies of indicated viruses (GarV-B-61.9%; GarV-C-36.5%; ShVX-28.6%), whereas onion samples (n&#x2009;=&#x2009;33) were largely negative (ShVX-3.0%; GarV-B and GarV-C-not detected). Co-occurrence analysis within garlic revealed a nested allexivirus module in which GarV-C and ShVX occurred only in GarV-B-positive plants. RT-PCR and Sanger sequencing generated 11 partial genomes representing GarV-B, GarV-C, ShVX, GarV-A and GarV-D. Maximum-likelihood phylogenies placed Ukrainian allexivirus isolates within established global diversity and indicated both European- and Asian-affiliated lineages. These findings provide the first evidence of allexiviruses in Ukrainian allium crops, and support their inclusion in plant health surveillance and planting-material certification.

High temperatures have been associated with occupational injuries (OIs). However, studies projecting future OIs under climate change scenarios are scarce, particularly in Europe. To fill this gap, we estimated projected heat-related OIs in 87 Italian cities under climate and demographic scenarios. OIs occurring from 2014 to 2019 were collected from the Italian national archive. Daily counts of OIs in each city were merged with ERA5-land Copernicus mean temperatures. City-specific exposure-response functions were estimated using a time-series analysis with distributed lag non-linear model (dlnm) and then meta-analysed to obtain a national estimate. This estimate was applied to project heat-attributable OIs from 2015 to 2100 using downscaled daily temperatures from 19 general circulation models, under three European Shared Socioeconomic Pathways (SSP) scenarios (SSP1-2.6; SSP2-4.5; SSP3-7.0), including demographic projections. Adaptation scenarios were also considered by applying risk attenuation. Under the lowest mitigation scenario (SSP3-7.0), an increase in the attributable number of OIs is foreseen, with 537 (95% CI 365-709) additional cases in 2070-2079 compared with the baseline decade 2010-2019, corresponding to an attributable relative fraction of 0.38% (95% CI 0.26-0.5). Under the intermediate scenario (SSP2-4.5), 464 (95%CI 312-616) additional cases are projected compared with baseline. Agriculture showed high vulnerability with attributable fraction of 1.20% (95% CI 0.99-1.41) under SSP3-7.0 scenario in 2070-2079. Heat-related OIs are predicted to increase under future climatic conditions. Workplace mitigation measures and public health actions are recommended to reduce heat-attributable OIs.

Second generation tyrosine kinase inhibitors (TKIs) have improved response rates in patients with chronic phase chronic myeloid leukaemia (CP-CML). Phase 2 trials demonstrated increased deep molecular response rates when combining second generation TKIs with pegylated interferon alfa (Peg-IFN). This trial aimed to evaluate the efficacy and the safety of combining nilotinib with Peg-IFN alfa-2a in patients with newly diagnosed CP-CML. In PETALs, this open-label, randomised, multicentre phase 3 trial, we enrolled patients with newly diagnosed CP-CML from 27 French academic institutions via a centrally-generated electronic system in a 1:1 ratio to two groups: 300 mg oral nilotinib alone twice a day (the nilotinib only group) or 300 mg nilotinib twice a day combined with subcutaneous Peg-IFN (30 &#x3bc;g per week for the first month of treatment and 45 &#x3bc;g per week thereafter) for a maximum of 2 years. The randomly allocated patients were stratified by their Sokal index and European Treatment and Outcome Study long-term survival index. Eligible patients had major BCR::ABL1 transcripts, an Eastern Cooperative Oncology Group performance score of two or lower, who had never received TKIs, and were aged between 18 and 65 years. The primary endpoint was the cumulative rate of molecular response 4&#xb7;5 (MR4&#xb7;5; defined as BCR::ABL1 international scale [IS] of 0&#xb7;0032% and lower), analysed in the intention-to-treat population (n=200). This trial is registered at ClinicalTrials.gov, NCT02201459, and is completed. 205 patients were enrolled between Aug 6, 2014, and Sept 29, 2016, after which five patients were declared ineligible and excluded, resulting in 200 patients being randomly allocated (99 to the nilotinib group and 101 to the combination group). The median age at diagnosis was 45 years (IQR 36-55); 130 patients (65%) were male and 70 (35%) were female. Median follow-up in this cohort was 67 months (IQR 32&#xb7;6-70&#xb7;6). The primary objective was met, with higher rates of MR4&#xb7;5 in the combination group (24% [95% CI 16&#xb7;0-34&#xb7;1] vs 15% [8&#xb7;6-24&#xb7;2], p=0&#xb7;048) at month 12. There were equivalent grade 3-4 haematological side effects in the both groups (14 vs 14) with a predominance for grade 3-4 thrombocytopenia without haemorrhages (six in the combination group vs five in the nilotinib group). Psychiatric grade 3-4 events occurred in six (6%) patients in the combination group (including three unsuccessful suicide attempts) compared with five (5%) in the nilotinib group (including one unsuccessful suicide attempt). Six vascular events also occurred in six patients in the combination group and seven vascular events in five patients in the nilotinib group (all grades 3-4). In this setting, Peg-IFN combined with nilotinib induced higher initial rates of MR4&#xb7;5 compared to TKI monotherapy, despite additional side effects. The onset of psychiatric events might promote immediate cease of Peg-IFN and psychiatrist advice Whether this early molecular response translates into sustained treatment-free survival should be studied in a randomised trial sufficiently powered for this outcome. Novartis Pharma.

To translate and cross-culturally adapt the Rapid Prime Diet Quality Score Screener (rPDQS) for use in Spanish primary care. Translation, cross-cultural adaptation and pilot testing. SITE: Mallorca Primary Care Centers. Primary care professionals and healthcare university students (n=29) and patients from primary care (n=71). Administration of the rPDQS for cognitive debriefing and pilot testing in primary care. Translation and cultural adaptation followed ISPOR and Beaton guidelines, including forward translation, synthesis, back-translation, expert review, pretesting, and final evaluation. Pretesting comprised cognitive debriefing and pilot testing in primary care to assess comprehension, cultural relevance, feasibility, and acceptability. Only minor linguistic and cultural refinements were required, such as refinement of cooking terms and inclusion of culturally familiar examples, without modifying the underlying constructs of the original instrument. One item relating to full-fat dairy products was identified as inconsistent with current Spanish/European dietary guidelines and was therefore removed from scoring. Examples of sweetened dairy products were added to better capture free-sugar intake. In pilot testing, the Spanish rPDQS showed good acceptability and feasibility. The mean completion time was 7min, <10% of participants required assistance, and 92% rated items as clear and culturally appropriate. Women had higher numeric scores than men, higher education and lower BMI were associated with better diet quality. The Spanish version of the rPDQS shows strong linguistic, conceptual, and cultural equivalence with the original instrument and represents a feasible, clear, and culturally appropriate tool for assessing diet quality in Spanish primary care.

Air pollution is currently one of the major environmental problems related to human health, affecting many diseases. In this regard, while studies have established an association between air quality and Type 2 Diabetes Mellitus (T2DM), there is still a need to refine exposure-response functions. Therefore, this study aims to establish the exposure-response function that relates the concentration of two air pollutants (NO2 and PM2.5) to the hazard ratio associated with acquiring T2DM, based on various cohort studies conducted worldwide. To achieve this, a methodology using nonlinear function adjustments will be employed. This function is then applied to determine the number of T2DM cases attributable to air pollution across Europe for different age groups, using atmospheric concentrations from 1991 to 2020. Results indicate a significant nonlinear relationship between pollutant exposure and T2DM cases, with higher risks observed in areas with elevated levels of NO2 and PM2.5 (specifically, in large European cities and in central Europe, mainly related to traffic and industrial activities). NO2 relates to 3754000 [3428000 - 3957000; 95% CI] annual T2DM cases, which represent 0.51% [0.46%-0.54%; 95% CI]; while PM2.5, annual cases increase to 5109000 [4036000 - 6581000; 95% CI], corresponding to a 0.69% [0.55%-0.89%; 95% CI] of cases of T2DM attributable to this pollutant. The analysis revealed that, despite lower concentrations, PM2.5 shows a higher impact on T2DM incidence compared to NO2, especially at lower exposure levels. Findings underscore the need for stringent air quality regulations, particularly in urban and industrial regions, to mitigate air pollution's health impacts.

The recent introduction of the right to oncological oblivion in some European states raises critical issues. While designed to protect cancer survivors from discrimination, this right may compromise occupational health surveillance for workers exposed to carcinogenic hazards. This commentary raises questions for future policy and research.

A position paper released by the European Association of Nuclear Medicine emphasised the need for multidisciplinary engagement to establish dosimetry-based personalised treatment in Radionuclide therapy (RNT). The uncertainty analysis results often ignored in routine clinical practice should be incorporated into the dose calculations to improve the efficacy and accuracy of treatment. In this study, patients with haematological malignancies undergoing radioimmunotherapy were evaluated. Our study aimed to calculate the uncertainties associated with each parameter of the single time point (STP) dosimetry chain and compare the with multiple time points (MTP) in the bone marrow and liver results. 28 patients received an intravenous injection of 111In-besilesomab (0.17&#x2009;&#xb1;&#x2009;0.01GBq) for pre-therapeutic dosimetry and were subsequently treated with 90Y-besilesomab(2.43&#x2009;&#xb1;&#x2009;0.53GBq). A dosimetry analysis was performed on bone marrow (BM) and liver with MTP and STP. We investigated the uncertainty in population mean effective half-life, volume, recovery coefficient, counts, measured activity, fitting parameters, time-integrated-activity, S-factors, and absorbed dose (AD) for a group of patients. The mean absorbed dose per unit administered activity (DpA) to BM was 5.8&#x2009;&#xb1;&#x2009;1.7 mGy/MBq with MTP and 5.8&#x2009;&#xb1;&#x2009;1.6 mGy/MBq with STP, and to the liver was 2.9&#x2009;&#xb1;&#x2009;1.9 mGy/MBq with MTP and 3.1&#x2009;&#xb1;&#x2009;2.4 mGy/MBq with STP. The mean fractional uncertainty associated with total absorbed dose to BM was 13.18&#x2009;&#xb1;&#x2009;3.46% with MTP and 18.75&#x2009;&#xb1;&#x2009;3.22% with STP, and to liver was 5.77&#x2009;&#xb1;&#x2009;3.13% with MTP and 49.78&#x2009;&#xb1;&#x2009;25.36% with STP. A moderate positive relationship (R2&#x2009;=&#x2009;0.7) was noted between post-injection acquisition time and AD uncertainty with STP for BM, whereas a strong positive relationship (R2&#x2009;=&#x2009;1) was noted for the liver. The absorbed dose uncertainty in STP was significantly higher compared to the MTP. Incorporating the uncertainty analysis for STP dosimetry parameters in routine clinical practice is strongly recommended. The accuracy in the acquisition time, population-based half-life and fitting function for time activity curve is vital for minimising uncertainty in STP dosimetry, which is less time-consuming and easier to implement in clinical practice than MTP.

Respiratory epidemics often place substantial pressure on intensive care units (ICU), which are continuously challenged to managing acute and life-threatening conditions under unpredictable workloads. During these periods, ICUs usually exhibit inefficient patient flows, treatment delays, and critical resource shortages. Proactive decision-making and precise interventions are therefore pivotal for patient survival and minimizing long-term sequelae. This paper proposes a robust approach combining Artificial Intelligence (AI), Bayesian Optimization, and Digital Twin (DT) to support ICU patient flow management. An eXtreme Gradient Boosting (XGBoost) algorithm is used to predict the patient transfer probability from the emergency department (ED) to the ICU within the next 24&#xa0;h. Bayesian optimization is employed for efficient hyperparameter tuning of the XGBoost model. Then, the transfer predictions are inserted into a DT to verify ICU capacity for timely care and design interventions for process mismatches. A case study from a European healthcare group validates the proposed approach. The specificity of the prediction XGBoost model was 94.90% (CI 95% 91.72% - 97.11%), whereas the sensitivity was 81.55% (CI 95% 72.70% - 88.51%). Finally, the median ICU bed waiting time decreased to between 66.74 and 69.38&#xa0;h after implementing a patient transfer policy with a partner hospital having available ICU beds. This study demonstrates the effectiveness of AI-DT in predicting the probability of ICU transfers, assessing the operational response of emergency wards and intensive care units, and crafting practical scenarios for enhancing patient flow management.