BACKGROUND: Person-centred care (PCC) is a fundamental principle in general practice, emphasising practices tailored to individual patient preferences, needs, and values. Despite the importance of PCC, general practitioners (GPs) face obstacles in effectively implementing it, with associated factors remaining unclear. OBJECTIVES: The PACE GP/FP study aims to explore GPs' attitudes towards PCC and the factors facilitating or hindering its implementation in daily practice across European countries. This paper outlines the PACE GP/FP study protocol. METHODS: The cross-sectional design with data collection via an online survey distribution to GPs in 24 European countries. Study instruments include two validated questionnaires (Perceived Stress Scale (PSS) and Patient Physician Orientation Scale (PPOS)) and additional items covering general information about the doctor and their practice, as well as facilitators and barriers to PCC. These additional items were specifically developed for the study, translated using the forward-backward method, evaluated through cognitive debriefing, and integrated into the REDCap platform to create language and country-specific survey links. The STROBE checklist guides the reporting of the manuscript. CONCLUSION: The PACE GP/FP study will provide a comprehensive exploration of GPs' attitudes towards PCC and the factors shaping its practice in Europe. The findings from the PACE GP/FP study will provide evidence for designing future implementation strategies and guide targeted interventions to promote PCC in primary care across Europe.
- Klíčová slova
- Primary health care, general practice, person-centred care,
- MeSH
- lidé MeSH
- péče orientovaná na pacienta * organizace a řízení MeSH
- postoj zdravotnického personálu * MeSH
- praktické lékařství * MeSH
- praktičtí lékaři * psychologie MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND AND OBJECTIVE: Cholangiocarcinoma (CCA) is a heterogeneous neoplasm of the biliary epithelium that easily infiltrates, metastasises and recurs. Magnesium disbalance is a hallmark of CCA, with the magnesium transporter cyclin M4 (CNNM4) being a key driver of various hepatic diseases. This study aims to unravel the role of CNNM4 in the initiation and progression of CCA. DESIGN: CNNM4 protein and gene expression were assessed in vitro, in vivo and in patients with CCA. Silencing of CNNM4 was effectively achieved by using small interfering RNA (siRNA) or short hairpin RNA in CCA cell lines and GalNAc-conjugated siRNA in a transposon-based CCA mice model. The impact of CNNM4 on tumour cell proliferation, migration and invasion to the lungs was evaluated using the chicken chorioallantoic membrane model. Proteomic analysis was employed to elucidate the underlying molecular mechanisms. RESULTS: CNNM4 was upregulated in CCA samples from humans, mice and cell lines. Functional studies demonstrated that CNNM4 deficiency attenuates cell growth, chemoresistance, migration, invasion, cancer stem cell properties and Warburg effect in vitro and in vivo. Proteomic analysis identified nuclear protein 1 as an upstream regulator of CNNM4-induced ferroptosis in CCA, ultimately leading to cell death. The iron chelator deferiprone could reverse the decreased proliferation induced by CNNM4 silencing, while inhibition of the heme oxygenase-1 by zinc protoporphyrin IX affected only the growth of cells with no targeted CNNM4 inhibition, highlighting the specificity of ferroptosis in CNNM4-associated effects. CONCLUSION: This study reveals that increased CNNM4 expression drives CCA progression and malignancy and that its inhibition may be an effective therapeutic strategy to limit proliferation and metastasis in patients with CCA.
- Klíčová slova
- CHOLANGIOCARCINOMA, GENE THERAPY, IRON METABOLISM, REACTIVE OXYGEN SPECIES,
- Publikační typ
- časopisecké články MeSH
Higher-order interactions underlie complex phenomena in systems such as biological and artificial neural networks, but their study is challenging due to the scarcity of tractable models. By leveraging a generalisation of the maximum entropy principle, we introduce curved neural networks as a class of models with a limited number of parameters that are particularly well-suited for studying higher-order phenomena. Through exact mean-field descriptions, we show that these curved neural networks implement a self-regulating annealing process that can accelerate memory retrieval, leading to explosive order-disorder phase transitions with multi-stability and hysteresis effects. Moreover, by analytically exploring their memory-retrieval capacity using the replica trick, we demonstrate that these networks can enhance memory capacity and robustness of retrieval over classical associative-memory networks. Overall, the proposed framework provides parsimonious models amenable to analytical study, revealing higher-order phenomena in complex networks.
- Publikační typ
- časopisecké články MeSH
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with underlying inflammatory bowel disease (IBD). This study investigates how PSC predisposes individuals to altered inflammatory immune responses compared with IBD alone. A case-control study was conducted with a cohort of 75 patients, including 16 with PSC (14 with concomitant IBD), 39 with IBD alone, and 20 controls. Serum bile acid profile, proteomic analysis, and immune-related gene expression in the colon tissue were examined. Colonic tissue from PSC patients exhibited up-regulation of immune regulation and inflammatory signaling mRNA markers, including LGR5, IL-8, CCL2, COX2, TWIST1, and SNAIL. Additionally, PSC patients displayed a distinct proinflammatory serum proteomic signature and moderate elevation of some bile acids, such as glycochenodeoxycholic acid (GCDCA). Co-incubation of human-derived monocytes with GCDCA partially replicated the inflammatory profile observed in PSC. These findings suggest that circulating bile acids modulate the peripheral immune system proinflammatory response, contributing to the unique PSC phenotype.
- Klíčová slova
- GCDCA, IBD, PSC, bile acids, immune response,
- MeSH
- dospělí MeSH
- idiopatické střevní záněty * imunologie komplikace krev genetika MeSH
- kolon metabolismus imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monocyty imunologie metabolismus MeSH
- proteomika metody MeSH
- sklerozující cholangitida * imunologie krev komplikace genetika MeSH
- studie případů a kontrol MeSH
- žlučové kyseliny a soli * krev imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- žlučové kyseliny a soli * MeSH
Soil biota is essential for forest ecosystems' functioning as it plays a key role in litter decomposition, nutrient recycling, and soil carbon sequestration. Since forest disturbances can have major impacts on soil biota and associated ecosystem services, there is an urgent need to provide evidence on its ecological responses to such disturbances. To this end, we established an experimental site to study the impacts of disturbance on soil biota abundance and properties resulting from tree-felling interventions of different intensity as well as from post-disturbance treatments (adding slash or not to the soil) in a Quercus faginea Lam. forest located in northern Spain. The experimental design consisted of a randomized block design that included five treatments: control, 50% canopy disturbance with and without slash, and 100% canopy disturbance with and without slash. Comprehensive inventories of soil biota, including microbes, microfauna, mesofauna, and macrofauna, were carried out after one, nine, and 21 months following the disturbance. Our results showed how body size determined the response of the soil community to canopy disturbance intensity and time since disturbance. Generally, the effects of the disturbance treatments were more severe as the size of the organisms increased and as the disturbance intensity increased. We conclude that while forests may show a certain capacity to absorb disturbances, assisting soils with slash addition after disturbances helps maintain habitats and the soil microclimatic conditions to conserve soil biota and functions. Moreover, organism body size emerges as a potential integrative functional trait indicative of responses to disturbance. Our results, derived from a quite unique multi-taxon study, have important implications not only for biodiversity conservation but also for forest managers and policymakers.
- Klíčová slova
- body‐size, forest disturbance, microorganisms, post‐disturbance, slash, soil fauna, soil microclimate,
- MeSH
- biodiverzita MeSH
- dub (rod) * fyziologie MeSH
- lesnictví * metody MeSH
- lesy * MeSH
- půda * chemie MeSH
- půdní mikrobiologie * MeSH
- společenstvo * MeSH
- stromy * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Španělsko MeSH
- Názvy látek
- půda * MeSH
Effective population size (Ne) is one of the most important parameters in evolutionary biology, as it is linked to the long-term survival capability of species. Therefore, Ne greatly interests conservation geneticists, but it is also very relevant to policymakers, managers, and conservation practitioners. Molecular methods to estimate Ne rely on various assumptions, including no immigration, panmixia, random sampling, absence of spatial genetic structure, and/or mutation-drift equilibrium. Species are, however, often characterized by fragmented populations under changing environmental conditions and anthropogenic pressure. Therefore, the estimation methods' assumptions are seldom addressed and rarely met, possibly leading to biased and inaccurate Ne estimates. To address the challenges associated with estimating Ne for conservation purposes, the COST Action 18134, Genomic Biodiversity Knowledge for Resilient Ecosystems (G-BiKE), organized an international workshop that met in August 2022 in Brașov, Romania. The overarching goal was to operationalize the current knowledge of Ne estimation methods for conservation practitioners and decision-makers. We set out to identify datasets to evaluate the sensitivity of Ne estimation methods to violations of underlying assumptions and to develop data analysis strategies that addressed pressing issues in biodiversity monitoring and conservation. Referring to a comprehensive body of scientific work on Ne, this meeting report is not intended to be exhaustive but rather to present approaches, workshop findings, and a collection of papers that serve as fruits of those efforts. We aimed to provide insights and opportunities to help bridge the gap between scientific research and conservation practice.
The scanning tunneling microscope (STM) provides access to atomic-scale properties of a conductive sample. While single-molecule tip functionalization has become a standard procedure, fluorescent molecular probes remained absent from the available tool set. Here, the plasmonic tip of an STM is functionalized with a single fluorescent molecule and is scanned on a plasmonic substrate. The tunneling current flowing through the tip-molecule-substrate junction generates a narrow-line emission of light corresponding to the fluorescence of the negatively charged molecule suspended at the apex of the tip, i.e., the emission of the excited molecular anion. The fluorescence of this molecular probe is recorded for tip-substrate nanocavities featuring different plasmonic resonances, for different tip-substrate distances and applied bias voltages, and on different substrates. We demonstrate that the width of the emission peak can be used as a probe of the exciton-plasmon coupling strength and that the energy of the emitted photons is governed by the molecule interactions with its environment. Additionally, we theoretically elucidate why the direct contact of the suspended molecule with the metallic tip does not totally quench the radiative emission of the molecule.
- Publikační typ
- časopisecké články MeSH
Twist engineering has emerged as a powerful approach for modulating electronic properties in van der Waals heterostructures. While theoretical works have predicted the modulation of spin texture in graphene-based heterostructures by twist angle, experimental studies are lacking. Here, by performing spin precession experiments, we demonstrate tunability of the spin texture and associated spin-charge interconversion with twist angle in WSe2/graphene heterostructures. For specific twist angles, we detect a spin component radial with the electron's momentum, in addition to the standard orthogonal component. Our results show that the helicity of the spin texture can be reversed by twist angle, highlighting the critical role of the twist angle in the spin-orbit properties of WSe2/graphene heterostructures and paving the way for the development of spin-twistronic devices.
- Publikační typ
- časopisecké články MeSH
Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. However, genetic diversity has been largely neglected in biodiversity monitoring, and when addressed, it is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. We report an accounting of efforts to monitor population genetic diversity in Europe (genetic monitoring effort, GME), the evaluation of which can help guide future capacity building and collaboration towards areas most in need of expanded monitoring. Overlaying GME with areas where the ranges of selected species of conservation interest approach current and future climate niche limits helps identify whether GME coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area, financial resources and conservation policy influence GME, high values of which only partially match species' joint patterns of limits to suitable climatic conditions. Populations at trailing climatic niche margins probably hold genetic diversity that is important for adaptation to changing climate. Our results illuminate the need in Europe for expanded investment in genetic monitoring across climate gradients occupied by focal species, a need arguably greatest in southeastern European countries. This need could be met in part by expanding the European Union's Birds and Habitats Directives to fully address the conservation and monitoring of genetic diversity.
- MeSH
- ekosystém MeSH
- genetická variace MeSH
- klimatické změny * MeSH
- zachování přírodních zdrojů * metody MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
