41 research outputs found
Important steps towards a big change for lung health: a joint approach by the European Respiratory Society, the European Society of Radiology and their partners to facilitate implementation of the European Union's new recommendations on lung cancer screening.
Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening. https://bit.ly/3J4O0Jb
Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat
Nádory tlustého střeva a konečníku patří mezi nejčastější onkologické diagnózy. V České republice je každoročně nově diagnostikováno téměř 8 500 pacientů s kolorektálním karcinomem a přibližně 3 900 osob tomuto onemocnění každým rokem podlehne. Celková prevalence přesáhne v roce 2012 hranici 55 000 osob. Společenské, etické i ekonomické důsledky vyplývající z takto vysoké zátěže jsou zřejmé. Publikace „Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat“ přináší ucelený přehled epidemiologické a léčebné zátěže české populace touto chorobou a věnuje se krátkodobým a dlouhodobým predikcím dalšího vývoje. Situace je rovněž hodnocena v mezinárodním srovnání, neboť v hodnotách incidence a mortality kolorektálního karcinomu obsazuje ČR přední příčky evropských i světových statistik. Z mezinárodních studií však také vyplývá pozitivní poznatek, že většině nádorů tlustého střeva a konečníku lze předejít účinnou prevencí. Kromě primární prevence je zde hlavním nástrojem organizovaný populační screening, který je založen na testech krvácení do stolice a na kolonoskopii. Otázkám prevence a výsledkům screeningu kolorektálního karcinomu jsou v publikaci věnovány zvláštní kapitoly. Ačkoli nejnovější data dokládají rostoucí výkonnost českého screeningu, celkově dosažené pokrytí populace bohužel stále není dostatečné. To platí pro včasný záchyt kolorektálního karcinomu obecně, neboť v ČR je setrvale téměř 50 % nových onemocnění diagnostikováno v pokročilých klinických stadiích, a tedy s výrazně sníženou šancí na vyléčení nebo dlouhodobé přežití pacienta. Publikace rovněž hodnotí přežití dosahované u českých pacientů jakožto zásadní ukazatel výsledků léčebné péče, u kterého v posledních 15 letech zaznamenáváme statisticky významné zlepšení. Pravděpodobnost 5letého relativního přežití je u včasně diagnostikovaného kolorektálního karcinomu v klinickém stadiu i vyšší než 88%. Tato čísla opět potvrzují nutnost účinné prevence a posílení screeningu tohoto preventabilního onemocnění. V tomto směru má publikace ambici informovat odbornou i laickou veřejnost, a proto věnuje značný prostor přehledu dostupných informačních zdrojů.The book aims to inform expert and general public about epidemiology of colorectal carcinoma in the Czech Republic and priorities resulting from high population burden for prevention, diagnostics, and treatment of this severe disease. A number of invited experts assess selected information sources that representatively describe performance and quality of preventive programmes and results of CRC treatment in the Czech Republic
Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
Understanding protein structure is of crucial importance in science, medicine
and biotechnology. For about two decades, knowledge based potentials based on
pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been
center stage in the prediction and design of protein structure and the
simulation of protein folding. However, the validity, scope and limitations of
these potentials are still vigorously debated and disputed, and the optimal
choice of the reference state -- a necessary component of these potentials --
is an unsolved problem. PMFs are loosely justified by analogy to the reversible
work theorem in statistical physics, or by a statistical argument based on a
likelihood function. Both justifications are insightful but leave many
questions unanswered. Here, we show for the first time that PMFs can be seen as
approximations to quantities that do have a rigorous probabilistic
justification: they naturally arise when probability distributions over
different features of proteins need to be combined. We call these quantities
reference ratio distributions deriving from the application of the reference
ratio method. This new view is not only of theoretical relevance, but leads to
many insights that are of direct practical use: the reference state is uniquely
defined and does not require external physical insights; the approach can be
generalized beyond pairwise distances to arbitrary features of protein
structure; and it becomes clear for which purposes the use of these quantities
is justified. We illustrate these insights with two applications, involving the
radius of gyration and hydrogen bonding. In the latter case, we also show how
the reference ratio method can be iteratively applied to sculpt an energy
funnel. Our results considerably increase the understanding and scope of energy
functions derived from known biomolecular structures
Estimating the number of colorectal cancer patients treated with anti-tumour therapy in 2015: the analysis of the Czech National Cancer Registry
<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) represents a serious health care problem in the Czech Republic, introducing a need for a prospective modelling of the incidence and prevalence rates. The prevalence of patients requiring anti-tumour therapy is also of great importance, as it is directly associated with planning of health care resources.</p> <p>Methods</p> <p>This work proposes a population-based model for the estimation of stage-specific prevalence of CRC patients who will require active anti-tumour therapy in a given year. Its applicability is documented on records of the Czech National Cancer Registry (CNCR), which is used to estimate the number of patients potentially treated with anti-tumour therapy in the Czech Republic in 2015.</p> <p>Results</p> <p>Several scenarios are adopted to cover the plausible development of the incidence and survival rates, and the probability of an anti-tumour therapy initiation. Based on the scenarios, the model predicts an increase in CRC prevalence from 13% to 30% in comparison with the situation in 2008. Moreover, the model predicts that 10,074 to 11,440 CRC patients will be indicated for anti-tumour therapy in the Czech Republic in 2015. Considering all patients with terminal cancer recurrence and all patients primarily diagnosed in stage IV, it is predicted that 3,485 to 4,469 CRC patients will be treated for the metastatic disease in 2015, which accounts for more than one third (34-40%) of all CRC patients treated this year.</p> <p>Conclusions</p> <p>A new model for the estimation of the number of CRC patients requiring active anti-tumour therapy is proposed in this paper. The model respects the clinical stage as the primary stratification factor and utilizes solely the population-based cancer registry data. Thus, no specific hospital data records are needed in the proposed approach. Regarding the short-term prediction of the CRC burden in the Czech Republic, the model confirms a continuous increase in the burden that must be accounted for in the future planning of health care in the Czech Republic.</p
Allosteric Transitions of Supramolecular Systems Explored by Network Models: Application to Chaperonin GroEL
Identification of pathways involved in the structural transitions of biomolecular
systems is often complicated by the transient nature of the conformations
visited across energy barriers and the multiplicity of paths accessible in the
multidimensional energy landscape. This task becomes even more challenging in
exploring molecular systems on the order of megadaltons. Coarse-grained models
that lend themselves to analytical solutions appear to be the only possible
means of approaching such cases. Motivated by the utility of elastic network
models for describing the collective dynamics of biomolecular systems and by the
growing theoretical and experimental evidence in support of the intrinsic
accessibility of functional substates, we introduce a new method,
adaptive anisotropic network model (aANM),
for exploring functional transitions. Application to bacterial chaperonin GroEL
and comparisons with experimental data, results from action minimization
algorithm, and previous simulations support the utility of aANM
as a computationally efficient, yet physically plausible, tool for unraveling
potential transition pathways sampled by large complexes/assemblies. An
important outcome is the assessment of the critical inter-residue interactions
formed/broken near the transition state(s), most of which involve conserved
residues
Extensive morphological and behavioural diversity among fourteen new and seven described species in Phytophthora Clade 10 and its evolutionary implications
During extensive surveys of global Phytophthora diversity 14 new species detected in natural ecosystems in Chile, Indonesia, USA (Louisiana), Sweden, Ukraine and Vietnam were assigned to Phytophthora major Clade 10 based on a multigene phylogeny of nine nuclear and three mitochondrial gene regions. Clade 10 now comprises three subclades. Subclades 10a and 10b contain species with nonpapillate sporangia, a range of breeding systems and a mainly soil- and waterborne lifestyle. These include the previously described P. afrocarpa, P. gallica and P. intercalaris and eight of the new species: P. ludoviciana, P. procera, P. pseudogallica, P. scandinavica, P. subarctica, P. tenuimura, P. tonkinensis and P. ukrainensis. In contrast, all species in Subclade 10c have papillate sporangia and are self-fertile (or homothallic) with an aerial lifestyle including the known P. boehmeriae, P. gondwanensis, P. kernoviae and P. morindae and the new species P. celebensis, P. chilensis, P. javanensis, P. multiglobulosa, P. pseudochilensis and P. pseudokernoviae. All new Phytophthora species differed from each other and from related species by their unique combinations of morphological characters, breeding systems, cardinal temperatures and growth rates. The biogeography and evolutionary history of Clade 10 are discussed. We propose that the three subclades originated via the early divergence of pre-Gondwanan ancestors > 175 Mya into water- and soilborne and aerially dispersed lineages and subsequently underwent multiple allopatric and sympatric radiations during their global spread
Genera of Phytopathogenic Fungi: GOPHY 4
This paper is the fourth contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions and information about the pathology, distribution, hosts and disease symptoms, as well as DNA barcodes for the taxa covered. Moreover, 12 whole-genome sequences for the type or new species in the treated genera are provided. The fourth paper in the GOPHY series covers 19 genera of phytopathogenic fungi and their relatives, including Ascochyta, Cadophora, Celoporthe, Cercospora, Coleophoma, Cytospora, Dendrostoma, Didymella, Endothia, Heterophaeomoniella, Leptosphaerulina, Melampsora, Nigrospora, Pezicula, Phaeomoniella, Pseudocercospora, Pteridopassalora, Zymoseptoria, and one genus of oomycetes, Phytophthora. This study includes two new genera, 30 new species, five new combinations, and 43 typifications of older names.The study of Ascochyta, Didymella and Leptosphaerulina
were supported by the National Natural Science Foundation of China
(31750001) and the National Science and Technology Fundamental
Resources Investigation Program of China (MOST: 2021FY100900).
The study of the genus Phytophthora was supported by the Project
Phytophthora Research Centre Reg. No. CZ.02.1.01/0.0/0.0/15_003/000
0453 cofinanced by the European Regional Development Fund. ShuaiFei
Chen acknowledges the National Key R&D Program of China (ChinaSouth Africa Forestry Joint Research Centre Project; 2018YFE0120900)
for financial support. Mounes Bakhshi and Rasoul Zare gratefully
acknowledge the Iran National Science Foundation (INSF), and Research
Deputy of the Iranian Research Institute of Plant Protection, Agricultural
Research, Education and Extension Organization (AREEO), for financial
support. The study of the genera Pseudocercospora and Pteridopassalora
were partially supported by JSPS KAKENHI Grant Numbers JP20K06146
to Chiharu Nakashima
Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity
Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF- B-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF- B signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity
The time is now: Achieving FH paediatric screening across Europe – The Prague Declaration
ReviewFamilial Hypercholesterolaemia (FH) is severely under-recognized, under-diagnosed and under-treated in Europe, leading to a significantly higher risk of premature cardiovascular diseases in those affected. FH stands for inherited, very high cholesterol and affects 1:300 individuals regardless of their age, race, sex, and lifestyle, making it the most common inherited metabolic disorder and a non-modifiable cardiovascular disease risk factor in the world..info:eu-repo/semantics/publishedVersio
Increasing Incidence of Geomyces destructans Fungus in Bats from the Czech Republic and Slovakia
BACKGROUND: White-nose syndrome is a disease of hibernating insectivorous bats associated with the fungus Geomyces destructans. It first appeared in North America in 2006, where over a million bats died since then. In Europe, G. destructans was first identified in France in 2009. Its distribution, infection dynamics, and effects on hibernating bats in Europe are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We screened hibernacula in the Czech Republic and Slovakia for the presence of the fungus during the winter seasons of 2008/2009 and 2009/2010. In winter 2009/2010, we found infected bats in 76 out of 98 surveyed sites, in which the majority had been previously negative. A photographic record of over 6000 hibernating bats, taken since 1994, revealed bats with fungal growths since 1995; however, the incidence of such bats increased in Myotis myotis from 2% in 2007 to 14% by 2010. Microscopic, cultivation and molecular genetic evaluations confirmed the identity of the recently sampled fungus as G. destructans, and demonstrated its continuous distribution in the studied area. At the end of the hibernation season we recorded pathologic changes in the skin of the affected bats, from which the fungus was isolated. We registered no mass mortality caused by the fungus, and the recorded population decline in the last two years of the most affected species, M. myotis, is within the population trend prediction interval. CONCLUSIONS/SIGNIFICANCE: G. destructans was found to be widespread in the Czech Republic and Slovakia, with an epizootic incidence in bats during the most recent years. Further development of the situation urgently requires a detailed pan-European monitoring scheme