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The European Commission has identified the role of Living Labs and Citizen Science as needed tools for the process of citizen-centric knowledge valorisation. Backed by the Memorandum of Understanding (MoU) between the European Citizen Science Association (ECSA) and the European Network of Living Labs (ENoLL) signed in 2023, this workshop seeked to bridge these two worlds for mutual benefit and increased societal impact. During the workshop, we (1) introduced the features of Living Labs; (2) co-created practical examples on how Citizen Science and Living Labs can provide joint contributions in support of green, social and digital transitions; and (3) started to identify action items where the ECSA and ENoLL communities join forces to empower citizens to become true change makers. Although providing important first insights, the workshop revealed a need to develop a better understanding of the relationships and possible mutual benefits between Citizen Science and Living Labs. Next steps include a follow up mirror workshop at Open Living Lab Days conference 2024.

Background and objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. Methods: We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. Key findings and limitations: We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63–75) and median PSA was 16 ng/ml (IQR 7.5–64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA

Abstract Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient’s treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer.

Abstract Climate warming is one of the facets of anthropogenic global change predicted to increase in the future, its magnitude depending on present-day decisions. The north Atlantic and Arctic Oceans are already undergoing community changes, with warmer-water species expanding northwards, and colder-water species retracting. However, the future extent and implications of these shifts remain unclear. Here, we fitted a joint species distribution model to occurrence data of 107, and biomass data of 61 marine fish species from 16,345 fishery independent trawls sampled between 2004 and 2022 in the northeast Atlantic Ocean, including the Barents Sea. We project overall increases in richness and declines in relative dominance in the community, and generalised increases in species’ ranges and biomass across three different future scenarios in 2050 and 2100. The projected decline of capelin and the practical extirpation of polar cod from the system, the two most abundant species in the Barents Sea, drove an overall reduction in fish biomass at Arctic latitudes that is not replaced by expanding species. Furthermore, our projections suggest that Arctic demersal fish will be at high risk of extinction by the end of the century if no climate refugia is available at eastern latitudes.

Resumen: El reto de encajar el perfil de los profesionales médicos con las necesidades de la sociedad se mantiene a lo largo de todo el período de formación de un médico. En el entorno actual, la sociedad presenta una evolución más rápida que los programas formativos. El presente artículo revisa los diferentes periodos de la formación de un médico, desde su acceso a la universidad hasta su salida al mercado laboral como médico especialista, reflexionando sobre hitos clave en este largo recorrido. Abstract: The challenge of matching the profile of medical professionals with the needs of society remains throughout the entire training period of a doctor. In the current environment, society is evolving faster than training programs. This article reviews the different periods of a doctor's training, from entering university to entering the labor market as a medical specialist, reflecting on key milestones in this long journey.

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Parenting is a key factor for the development of children with intellectual and developmental disabilities. Therefore, early intervention programs should target parenting behaviors to improve children's developmental outcomes. The present study analyzed the effect of parental behaviors and other family factors on the cognitive and linguistic development of children with an intellectual disability (ID). Participants (n = 87, aged between 20 and 47 months) were recruited from several Spanish Early Intervention Centers. The children's development was assessed with the Bayley Scales of Infant Development (BSID-III) on two occasions. Besides questionnaires including family factors, 10-min mother-child and father-child interactions during free play were auto-recorded at home. Intensive statistical modeling on the two measurement occasions was used to select relevant predictors as well as their interactions. Child cognitive development models, including predictors such as mother's responsiveness and affection and father's teaching, had a predictive capacity between 22 and 26%. The language development models, including the mother's responsiveness and father's teaching scores amongst other predictors, yielded adjusted-R[superscript 2]s between 26 and 28%. This study's findings evidence that parental behaviors during adult-child interaction affect the development of children with intellectual disabilities. The study also provides data that can be used to guide early intervention.

Background: Giant cell arteritis (GCA) is a heterogeneous disease with diverse clinical presentations and varying degrees of severity. This study aimed to assess the incidence of 3 clinical subsets in GCA and analyze associated severe complications and survival rates. By identifying distinct clinical patterns, the goal is to customize treatment approaches and minimize severe complications during follow-up. Methods: This retrospective study classified clinical manifestations of GCA into 3 major phenotypes based on the reason for consultation: i) cranial, ii) extracranial, and iii) occult GCA. These groups were analyzed and compared for acute complications, including severe ischemic complications, “true” occlusive disease, and late complications such as aortic aneurysm. Survival data were also collected during follow-up. Results: Visual disturbances were more common in the cranial GCA group compared to other subsets (P < .001). Blindness and stroke showed a clinically relevant trend, although statistical differences were not significant between the cranial GCA groups. Limb claudication was significantly more prevalent in the extracranial subset compared to the cranial or occult GCA subsets (12% vs. 2.6% vs. 0% respectively). Severe ischemic complications and true occlusive disease were more frequent in the cranial GCA groups (60%, P=.005 and 40%, P=1.64 respectively). Regarding mortality, there were no statistically significant differences in survival among the different clinical subsets. However, the occult GCA subset showed a trend towards a higher prevalence of deaths, both overall and specifically due to GCA. Conclusion: Clinical subsets in GCA present distinct complications and survival outcomes, with the cranial subset showing a higher incidence of severe ischemic events and the occult subset associated with delayed diagnosis and increased mortality. Recognizing these subsets is crucial for tailored treatment approaches and improving patient prognosis. Further prospective studies are needed to refine diagnostic and therapeutic strategies.

AbstractBackground Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing.Objectives To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD).Methods The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings.Results Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors.Conclusion Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.

Summary: The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) ‘Intellectual Disability, Autosomal Dominant 57’ (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a heterozygous TLK1 variant (c.1435C>G, p.Q479E), as well as a mutation in MDM1 (c.1197dupT, p.K400∗). Cells expressing TLK1 p.Q479E exhibited reduced cytokine responses and elevated DNA damage, but not increased radiation sensitivity or DNA repair defects. The TLK1 p.Q479E variant impaired kinase activity but not proximal protein interactions. Our study provides the first functional characterization of NDD-associated TLK1 variants and suggests that, such as TLK2, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.

iquaflow is a framework that provides a set of tools to assess image quality. The user can add custom metrics that can be easily integrated and a set of unsupervised methods is offered by default. Furthermore, iquaflow measures quality by using the performance of AI models trained on the images as a proxy. This also helps to easily make studies of performance degradation of several modifications of the original dataset, for instance, with images reconstructed after different levels of lossy compression; satellite images would be a use case example, since they are commonly compressed before downloading to the ground. In this situation, the optimization problem involves finding images that, while being compressed to their smallest possible file size, still maintain sufficient quality to meet the required performance of the deep learning algorithms. Thus, a study with iquaflow is suitable for such case. All this development is wrapped in Mlflow: an interactive tool used to visualize and summarize the results. This document describes different use cases and provides links to their respective repositories. To ease the creation of new studies, we include a cookiecutter repository. The source code, issue tracker and aforementioned repositories are all hosted on GitHub.

Abstract Objective To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real‐world setting. Methods The study is prospective and observational based on real‐world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and high‐risk non‐metastatic castration‐resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022. Results Of 227 patients treated with apalutamide, 10% had ECOG‐PS 2, and 41% were diagnosed with new‐generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment‐related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal‐therapies. Conclusions The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.

Histone H1 is involved in the regulation of chromatin structure. Human somatic cells express up to seven subtypes. The variability in the proportions of somatic H1s (H1 complement) is one piece of evidence supporting their functional specificity. Alterations in the protein levels of different H1 subtypes have been observed in cancer, suggesting their potential as biomarkers and that they might play a role in disease development. We have developed a mass spectrometry-based (MS) parallel reaction monitoring (PRM) assay suitable for the quantification of H1 subtypes. Our PRM method is based on the quantification of unique peptides for each subtype, providing high specificity. Evaluation of the PRM performance on three human cell lines, HeLa, K562, and T47D, showed high reproducibility and sensitivity. Quantification values agreed with the electrophoretic and Western blot data, indicating the accuracy of the method. We used PRM to quantify the H1 complement in peripheral blood samples of healthy individuals and chronic myeloid leukemia (CML) patients. In CML, the first line of therapy is a tyrosine kinase inhibitor, imatinib. Our preliminary data revealed differences in the H1 complement in CML patients between imatinib responders and non-responders. These results support further research to determine if the H1 content or subtype composition could help predict imatinib response.

Cerebrospinal fluid (CSF) is a fluid critical to brain development, function, and health. It is actively secreted by the choroid plexus, and it emanates from brain tissue due to osmolar exchange and the constant contribution of brain metabolism and astroglial fluid output to interstitial fluid into the ventricles of the brain. CSF acts as a growth medium for the developing cerebral cortex and a source of nutrients and signalling throughout life. Together with perivascular glymphatic and interstitial fluid movement through the brain and into CSF, it also acts to remove toxins and maintain metabolic balance. In this study, we focused on cerebral folate status, measuring CSF concentrations of folate receptor alpha (FOLR1); aldehyde dehydrogenase 1L1, also known as 10-formyl tetrahydrofolate dehydrogenase (ALDH1L1 and FDH); and total folate. These demonstrate the transport of folate from blood across the blood–CSF barrier and into CSF (FOLR1 + folate), and the transport of folate through the primary FDH pathway from CSF into brain FDH + ve astrocytes. Based on our hypothesis that CSF flow, drainage issues, or osmotic forces, resulting in fluid accumulation, would have an associated cerebral folate imbalance, we investigated folate status in CSF from neurological conditions that have a severity association with enlarged ventricles. We found that all the conditions we examined had a folate imbalance, but these folate imbalances were not all the same. Given that folate is essential for key cellular processes, including DNA/RNA synthesis, methylation, nitric oxide, and neurotransmitter synthesis, we conclude that ageing or some form of trauma in life can lead to CSF accumulation and ventricular enlargement and result in a specific folate imbalance/deficiency associated with the specific neurological condition. We believe that addressing cerebral folate imbalance may therefore alleviate many of the underlying deficits and symptoms in these conditions.

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.