Directorate-General Joint Research Centre

IntroductionGait kinematic analysis is essential for evaluating walking quality and efficacy of interventions. Spastic gait varies among individuals, even when they present similar postural gait patterns. While previous studies have reported functional gait improvements following repeated botulinum toxin-A (BT-A) injections, effects on gait kinematics remain unclear.MethodsThis prospective cohort study assessed sagittal gait kinematics in adults with chronic stroke-related multifocal spasticity, who received three cycles of progressively higher doses of Inco BT-A (400, 600, and 800 U). Quantified gait analysis (QGA) was performed before and after the first injection cycle and after the last. To account for inter-individual variability, sagittal kinematic variables that best reflected individual postural gait patterns were identified.ResultsTwenty-five participants were included. Sagittal kinematic improvements were not observed after the first injection cycle but became apparent after the third. Significant improvements were observed in two postural gait patterns: pes equinus during stance, with a mean increase in ankle dorsiflexion of 3° (SD = 6°, p = 0.008), and stiff knee gait, with a mean increase in knee flexion during swing of 7° (SD = 7°, p < 0.001).ConclusionThis study showed effects of progressively higher doses of BT-A on sagittal knee and ankle kinematics in individuals with multifocal spasticity after chronic stroke, suggesting that three cycles of progressively higher doses are necessary to achieve measurable kinematic improvements. These results align with functional gains from our larger study, underscoring the importance of individualized gait assessments in clinical decision-making on post-stroke spastic gait.

Background: Marginal bone loss (MBL) is a condition leading to implant loss and treatment failure. MBL is one of the main complications in dental implantology. The aim of this research is to show the method that can predict bone loss around implants and protect patients from implant loss. Methods: A total of 1026 intraoral standardized radiographs of dental implants were included in this study. A total of 2052 peri-implant jawbone image samples were analyzed in MaZda 4.6 software. A new scale was calculated and described. MBL was measured, and groups of patients were compared. Results: After 3 months of functional loading, the Corticalization Index (CI) was calculated to be 210.70 ± 149.78 and increased after 60 months to 277.88 ± 198.78. In the 60-month observation, MBL was 0.85 mm ± 1.29 mm, and it has been noted that low MBL is associated with CI lower than 300, high MBL with CI higher than 500, and critical high MBL appeared when CI was higher than 1200. Conclusions: Authors created a new scale, and research showed that the specified CI in our scale may predict MBL around dental implants with a five-year forecast horizon. It allows us to implement specific treatment and protect implants from loss.

This cross-sectional observational study aims to estimate the number of days absent from work due to health-related problems among employed individuals with multimorbidity and to quantify the lost productivity value from these absences. Data were obtained from the Belgian Health Interview Survey 2018, comprising employed individuals aged 15-64 (N = 4096). We examined 12 chronic conditions and 57 dyads. The Human Capital Approach was used by multiplying the reported number of days absent by the average wage per person per day, utilizing stratified gross wages from the Belgian Statistical Office. Approximately one-third of the study population reported multimorbidity. For individuals with zero to four+ chronic conditions, mean days of absence were 5.5 (95% CI: 2.3-8.8), 6.8 (95% CI: 2.9-10.7), 14.8 (95% CI: 10-19.6), 24 (95% CI: 17.8-30.2), and 36.2 (95% CI: 30.4-42), respectively. Depression (€3089; 95% CI: 2129-4049), diabetes (€2315; 95% CI: 962-3668), arthropathies (€1972; 95% CI: 1101-2844), and cancer (€1848; 95% CI: 598-3099), as standalone conditions, were associated with the greatest productivity losses. The effects were amplified up to seven times with the co-occurrence of multiple chronic conditions. We estimated 34.2 million days absent or €7.5 billion in lost productivity due to health-related work absenteeism among working-age employed individuals with multimorbidity in 2018. At the population level, the coexistence of two musculoskeletal disorders was linked to the highest aggregated productivity loss. At the individual level, the coexistence of a mental health condition and a somatic condition was associated with the highest average productivity loss per capita. The indirect cost due to health-related absence from work for individuals with multimorbidity in Belgium is high, and in many cases, exceeds the direct cost of treatment.

Most cells produce latent transforming growth factor-beta 1 (TGF-β1), but only very few activate the cytokine via cell type-specific mechanisms. TGF-β1 favors cancer progression by suppressing anti-tumor T cell responses. Which cells produce this immunosuppressive TGF-β1 in human tumors is unknown. Putative sources include cells expressing the glycoprotein A repetitions predominant (GARP) protein, comprising mostly activated regulatory T cells (Tregs) (GARP+FOXP3+ cells) and blood endothelial cells (BECs). We performed multiplexed immunohistofluorescence and computerized image analyses on 186 tumor samples from 5 cancer types (colorectal, urothelial, lung and breast primary carcinomas and melanoma metastases), compared to patient-matched adjacent non-cancerous tissues. GARP+ Tregs were present in 29–75% of the various types of tumor samples. Their proportion was higher in tumors than non-cancerous tissues but unexpectedly it did not correlate with that of tumor-infiltrating T lymphocytes (TILs). The density of blood vessels was similar across samples, with more than half expressing GARP. The proportion of cells undergoing TGF-β1 signaling, which express the phosphorylated form of mothers against decapentaplegic homolog 2 (pSMAD2), was approximately twice as high in tumors compared to non-cancerous tissues. In most tumor types, pSMAD2+ TILs were twice closer to the nearest FOXP3+ cell than after random repositioning, at a distance (~ 70 µm) consistent with short-range paracrine TGF-β1 signaling. In contrast, pSMAD2+ non-T cells and pSMAD2− TILs were not closer to FOXP3+ cells, neither were pSMAD2+ cells (TILs and others) to BECs. We conclude that, in human tumors, GARP-expressing Tregs rather than BECs appear to represent a source of TGF-β1 suppressing nearby TILs. This local immunosuppression could be blocked with anti-GARP:TGF-β1 antibodies, particularly to treat patients with tumors heavily infiltrated by GARP-expressing Tregs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04157-2.

Abstract Innovation is a driver in accelerating the transition to sustainable, healthy and inclusive food systems, from primary production to consumption. While it can contribute to developing solutions and overcoming barriers, it can also introduce potential emerging issues or risks related to new food or feed materials or new processing technologies. EFSA launched in 2021 a project to ensure preparedness for the assessment of safety of new food/feed sources and production technologies with the collaboration of the Joint Research Centre (JRC). The aim of this project was to evaluate whether signals of emerging technologies (‘weak signals’) in the field of new food/feed sources and innovative production technologies can be identified, combining the expertise and IT systems of JRC (TIM project) to detect weak signals with EFSA's expert knowledge to validate these signals. JRC's TIM Technology is a software dedicated to data analytics on innovation‐related data, which includes text‐mining features for documents and keywords analysis allowing for the detection of active topics and issues in sets of documents. A structured future‐thinking approach on weak signals in the area of new food/feed sources and production technologies can provide a better understanding of various challenges and potential emerging issues or risks in an extremely quickly evolving global context.