• MeSH
• epidermální růstový faktor fyziologie   MeSH
• keratinocyty fyziologie   účinky léků   MeSH
• obojživelníci MeSH
• pohyb buněk fyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

ncreased numbers of rosettes of podosomes were observed in overgrown rat Rous sarcoma RsK4 cells. A possible role of these structures in nutrient uptake in tumour cell survival was investigated by exposure to acute starvation. A single cell suspension of RsK4 cells in Hanks balanced salt solution was allowed to interact with either clean uncoated or serum-coated for bait coverglasses. Confocal microscopy revealed contrasting 3D cell morphologies that were associated with conspicuous patterns of podosomal structures, which on the coated coverglasses resembled the sealing zones of osteoclasts, while on the uncoated coverglasses they resembled the marginal podosomes of migrating monocyte-derived cells. Thus, the arising podosomal structures, the involvement of which in an uptake of nutrients appeared feasible morphologically, were associated with the emerging 3D cell shapes guided by the microenvironment. Such phenotypic plasticity of neoplastic RsK4 cells in response to microenvironmental challenge suggested that uniqueness in cellular attributes within the neoplastic cell population could be crucial for the malignant potential.

• MeSH
• aktiny metabolismus   MeSH
• buněčné výběžky fyziologie   metabolismus   MeSH
• financování organizované MeSH
• konfokální mikroskopie MeSH
• krysa rodu rattus MeSH
• kultivační média MeSH
• pohyb buněk fyziologie   MeSH
• potkani inbrední LEW MeSH
• ptačí sarkom metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

PURPOSE: Prostate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of "MRI-only" screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs. METHODS: This narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening. RESULTS: Several prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the "MRI-only" approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5-20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning). CONCLUSION: Although promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed.

• MeSH
• časná detekce nádoru metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory prostaty * diagnostické zobrazování   patologie   MeSH
• prospektivní studie MeSH
• prostatický specifický antigen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In many taxa, the most common form of sex-biased migration timing is protandry-the earlier arrival of males at breeding areas. Here we test this concept across the annual cycle of long-distance migratory birds. Using more than 350 migration tracks of small-bodied trans-Saharan migrants, we quantify differences in male and female migration schedules and test for proximate determinants of sex-specific timing. In autumn, males started migration about 2 days earlier, but this difference did not carry over to arrival at the non-breeding sites. In spring, males on average departed from the African non-breeding sites about 3 days earlier and reached breeding sites ca 4 days ahead of females. A cross-species comparison revealed large variation in the level of protandry and protogyny across the annual cycle. While we found tight links between individual timing of departure and arrival within each migration season, only for males the timing of spring migration was linked to the timing of previous autumn migration. In conclusion, our results demonstrate that protandry is not exclusively a reproductive strategy but rather occurs year-round and the two main proximate determinants for the magnitude of sex-biased arrival times in autumn and spring are sex-specific differences in departure timing and migration duration.

• MeSH
• migrace zvířat * MeSH
• ptáci fyziologie   MeSH
• roční období MeSH
• rozmnožování MeSH
• sexuální faktory MeSH
• zpěvní ptáci fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• severní Afrika MeSH

• Publikační typ
• abstrakt z konference MeSH

Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .

• MeSH
• dospělí MeSH
• emoce MeSH
• lidé MeSH
• mínění MeSH
• mladiství MeSH
• mladý dospělý MeSH
• psychologické modely MeSH
• sociální percepce etnologie   psychologie   MeSH
• srovnání kultur MeSH
• výraz obličeje MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

• MeSH
• adalimumab terapeutické užití   MeSH
• autoimunitní nemoci farmakoterapie   genetika   MeSH
• biologická terapie metody   MeSH
• biologické přípravky imunologie   terapeutické užití   MeSH
• celogenomová asociační studie metody   MeSH
• Crohnova nemoc farmakoterapie   genetika   MeSH
• dospělí MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• interferon beta 1a terapeutické užití   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• revmatoidní artritida farmakoterapie   genetika   MeSH
• rituximab terapeutické užití   MeSH
• roztroušená skleróza farmakoterapie   genetika   MeSH
• ulcerózní kolitida farmakoterapie   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• časové faktory MeSH
• chronická myeloidní leukemie farmakoterapie   patologie   MeSH
• imatinib mesylát terapeutické užití   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   patologie   MeSH
• míra přežití MeSH
• následné studie MeSH
• nenasazení léčby statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Currently, the deployment of tracking devices is one of the most frequently used approaches to study movement ecology of birds. Recent miniaturization of light-level geolocators enabled studying small bird species whose migratory patterns were widely unknown. However, geolocators may reduce vital rates in tagged birds and may bias obtained movement data. There is a need for a thorough assessment of the potential tag effects on small birds, as previous meta-analyses did not evaluate unpublished data and impact of multiple life-history traits, focused mainly on large species and the number of published studies tagging small birds has increased substantially. We quantitatively reviewed 549 records extracted from 74 published and 48 unpublished studies on over 7,800 tagged and 17,800 control individuals to examine the effects of geolocator tagging on small bird species (body mass <100 g). We calculated the effect of tagging on apparent survival, condition, phenology and breeding performance and identified the most important predictors of the magnitude of effect sizes. Even though the effects were not statistically significant in phylogenetically controlled models, we found a weak negative impact of geolocators on apparent survival. The negative effect on apparent survival was stronger with increasing relative load of the device and with geolocators attached using elastic harnesses. Moreover, tagging effects were stronger in smaller species. In conclusion, we found a weak effect on apparent survival of tagged birds and managed to pinpoint key aspects and drivers of tagging effects. We provide recommendations for establishing matched control group for proper effect size assessment in future studies and outline various aspects of tagging that need further investigation. Finally, our results encourage further use of geolocators on small bird species but the ethical aspects and scientific benefits should always be considered.

• MeSH
• fylogeneze MeSH
• migrace zvířat * MeSH
• ptáci * MeSH
• publikační zkreslení MeSH
• roční období MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH

BACKGROUND: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. METHODS: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. RESULTS: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18

• MeSH
• bipolární porucha * patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mánie MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• multicentrické studie jako téma MeSH
• neurozobrazování MeSH
• ztenčování mozkové kůry MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH