Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches-firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes-and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P-values and f3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f-statistic estimations.
- Klíčová slova
- f-statistics, aDNA, admixture, ancient DNA, archaeogenetics, paleogenomics, qpAdm,
- MeSH
- demografie MeSH
- genomika * metody MeSH
- modely genetické MeSH
- paleontologie * metody MeSH
- software MeSH
- správnost dat MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
- Klíčová slova
- epidemiology, granulomatosis with polyangiitis, quality indicators, health care, systemic vasculitis,
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie epidemiologie komplikace MeSH
- granulomatóza s polyangiitidou * farmakoterapie epidemiologie komplikace MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie epidemiologie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- registrace MeSH
- správnost dat MeSH
- ukládání a vyhledávání informací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Názvy látek
- protilátky proti cytoplazmě neutrofilů MeSH
In recent years, several international urological societies have published guidelines on the diagnosis, treatment, and follow-up of urethral strictures, but a guideline for the German-speaking region has not been available to date. This summary provides a detailed comparison of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA) and the Société Internationale d'Urologie (SIU) with regard to the treatment of anterior urethral strictures, i.e. from the bulbar urethra to the meatus. In the following work, differences and specific recommendations in the guidelines are highlighted. In particular, the three guidelines largely agree with regard to diagnostic workup and follow-up. However, divergences exist in the management of anterior urethral strictures, particularly with regard to the use of endoscopic therapeutic approaches and the use of urethral stents. In addition, the EAU provides more comprehensive and detailed recommendations on urethroplasty techniques and specific patient follow-up. The EAU guidelines are the most current and were the first to include instructions for urethral strictures in women and individuals with gender incongruence after genital approximation surgery. Reconstructive urology is a rapidly evolving specialty and, thus, the clinical approach has been changing accordingly. Although guideline recommendations have become more inclusive and comprehensive, more high-quality data are needed to further improve the level of evidence.
In den letzten Jahren haben verschiedene internationale urologische Fachgesellschaften Leitlinien zur Diagnostik, Behandlung und Nachsorge von Harnröhrenstrikturen veröffentlicht, eine Leitlinie für den deutschsprachigen Raum ist jedoch bis dato nicht verfügbar. Diese Zusammenfassung bietet einen detaillierten Vergleich der Leitlinien der European Association of Urology (EAU), American Urological Association (AUA) und der Société Internationale d’Urologie (SIU) im Hinblick auf die Behandlung anteriorer Harnröhrenstrikturen, also von der bulbären Harnröhre bis zum Meatus urethrae. In der folgenden Arbeit werden Unterschiede und exklusive Empfehlungen in den Leitlinien besonders herausgestellt. Insbesondere in Bezug auf die diagnostische Abklärung und Nachsorge stimmen die drei Leitlinien größtenteils überein. Divergenzen bestehen jedoch beim eigentlichen Management der anterioren Harnröhrenstrikturen, insbesondere in Bezug auf den Einsatz endoskopischer Therapieansätze und die Verwendung von Harnröhren-Stents. Darüber hinaus bietet die EAU umfassendere und detailliertere Empfehlungen zu Urethroplastiktechniken und der spezifischen Nachsorge der Patienten. Die EAU-Leitlinien sind die aktuellsten und die ersten, die Anweisungen für Harnröhrenstrikturen bei Frauen und Personen mit Geschlechtsinkongruenz nach genitalangleichender Operation beinhalten. Die rekonstruktive Urologie ist ein sich rasch weiterentwickelndes Fachgebiet und die klinische Vorgehensweise verändert sich dementsprechend dynamisch. Obwohl die Leitlinienempfehlungen inklusiver und umfassender geworden sind, sind weitere qualitativ hochwertige Daten erforderlich, um das Evidenzniveau weiter zu verbessern.
- Klíčová slova
- Endoscopy, Evidence-based medicine, Hypospadias, Patient-reported outcome measures, Urethroplasty,
- MeSH
- lidé MeSH
- správnost dat MeSH
- striktura uretry * diagnóza MeSH
- uretra chirurgie MeSH
- urologie * MeSH
- zákroky plastické chirurgie * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Spojené státy americké MeSH
Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.
- Klíčová slova
- COVID-19, ensemble forecast, forecasting, model evaluation,
- MeSH
- COVID-19 * mortalita MeSH
- lidé MeSH
- pandemie MeSH
- pravděpodobnost MeSH
- předpověď MeSH
- správnost dat MeSH
- veřejné zdravotnictví trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké epidemiologie MeSH
Ig gene (IG) clonality analysis has an important role in the distinction of benign and malignant B-cell lymphoid proliferations and is mostly performed with the conventional EuroClonality/BIOMED-2 multiplex PCR protocol and GeneScan fragment size analysis. Recently, the EuroClonality-NGS Working Group developed a method for next-generation sequencing (NGS)-based IG clonality analysis. Herein, we report the results of an international multicenter biological validation of this novel method compared with the gold standard EuroClonality/BIOMED-2 protocol, based on 209 specimens of reactive and neoplastic lymphoproliferations. NGS-based IG clonality analysis showed a high interlaboratory concordance (99%) and high concordance with conventional clonality analysis (98%) for the molecular conclusion. Detailed analysis of the individual IG heavy chain and kappa light chain targets showed that NGS-based clonality analysis was more often able to detect a clonal rearrangement or yield an interpretable result. NGS-based and conventional clonality analysis detected a clone in 96% and 95% of B-cell neoplasms, respectively, and all but one of the reactive cases were scored polyclonal. We conclude that NGS-based IG clonality analysis performs comparable to conventional clonality analysis. We provide critical parameters for interpretation and discuss a first step toward a quantitative scoring approach for NGS clonality results. Considering the advantages of NGS-based clonality analysis, including its high sensitivity and possibilities for accurate clonal comparison, this supports implementation in diagnostic practice.
- MeSH
- B-buněčný lymfom genetika MeSH
- B-lymfocyty imunologie MeSH
- buněčné klony imunologie MeSH
- fenotyp MeSH
- folikulární lymfom genetika MeSH
- genová přestavba * MeSH
- geny pro imunoglobuliny * MeSH
- imunoglobuliny - kappa-řetězce genetika MeSH
- lidé MeSH
- multiplexová polymerázová řetězová reakce metody MeSH
- senzitivita a specificita MeSH
- správnost dat MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
- Názvy látek
- imunoglobuliny - kappa-řetězce MeSH
- těžké řetězce imunoglobulinů MeSH
Honey consumption is attributed to potentially advantageous effects on human health due to its antioxidant capacity as well as anti-inflammatory and antimicrobial activity, which are mainly related to phenolic compound content. Phenolic compounds are secondary metabolites of plants, and their content in honey is primarily affected by the botanical and geographical origin. In this study, a high-resolution mass spectrometry (HRMS) method was applied to determine the phenolic profile of various honey matrices and investigate authenticity markers. A fruitful sample set was collected, including honey from 10 different botanical sources (n = 51) originating from Greece and Poland. Generic liquid-liquid extraction using ethyl acetate as the extractant was used to apply targeted and non-targeted workflows simultaneously. The method was fully validated according to the Eurachem guidelines, and it demonstrated high accuracy, precision, and sensitivity resulting in the detection of 11 target analytes in the samples. Suspect screening identified 16 bioactive compounds in at least one sample, with abscisic acid isomers being the most abundant in arbutus honey. Importantly, 10 markers related to honey geographical origin were revealed through non-targeted screening and the application of advanced chemometric tools. In conclusion, authenticity markers and discrimination patterns were emerged using targeted and non-targeted workflows, indicating the impact of this study on food authenticity and metabolomic fields.
- Klíčová slova
- UPLC–QToF-MS, authenticity, geographical origin, honey, metabolomics, origin discrimination, phenolic compounds,
- MeSH
- antioxidancia analýza izolace a purifikace MeSH
- benzaldehydy analýza izolace a purifikace MeSH
- cinnamáty analýza izolace a purifikace MeSH
- flavonoidy analýza izolace a purifikace MeSH
- hmotnostní spektrometrie metody MeSH
- hydroxybenzoáty analýza izolace a purifikace MeSH
- lidé MeSH
- med analýza MeSH
- metabolom * MeSH
- metabolomika metody MeSH
- senzitivita a specificita MeSH
- správnost dat MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
- Geografické názvy
- Polsko MeSH
- Řecko MeSH
- Názvy látek
- antioxidancia MeSH
- benzaldehydy MeSH
- cinnamáty MeSH
- flavonoidy MeSH
- hydroxybenzoáty MeSH
- vanillin MeSH Prohlížeč
The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.
- MeSH
- databáze proteinů * MeSH
- konformace proteinů MeSH
- shluková analýza MeSH
- software * MeSH
- správnost dat MeSH
- uživatelské rozhraní počítače MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.
- Klíčová slova
- B-lymphoblastoid cell lines, Human leukocyte antigen, International HLA and Immunogenetics Workshop, Multiple-laboratory testing, Next-generation sequencing,
- MeSH
- alely MeSH
- B-lymfocyty virologie MeSH
- exony genetika MeSH
- genetická variace MeSH
- genetické lokusy MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- histokompatibilita MeSH
- HLA antigeny genetika MeSH
- homozygot MeSH
- jednoduchá slepá metoda MeSH
- lidé MeSH
- MHC antigeny I. třídy genetika MeSH
- MHC antigeny II. třídy genetika MeSH
- sekvenční analýza DNA metody MeSH
- správnost dat MeSH
- testování histokompatibility metody MeSH
- transformované buněčné linie MeSH
- virová transformace buněk MeSH
- virus Epsteinův-Barrové imunologie MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- HLA antigeny MeSH
- MHC antigeny I. třídy MeSH
- MHC antigeny II. třídy MeSH
Amniotes possess variability in sex determination, from environmental sex determination (ESD), where no sex chromosomes are present, to genotypic sex determination (GSD) with highly differentiated sex chromosomes. Some evolutionary scenarios postulate high stability of differentiated sex chromosomes and rare transitions from GSD to ESD. However, sex chromosome turnovers and two independent transitions from highly differentiated ZZ/ZW sex chromosomes to ESD were previously reported in the lacertid lizards. Here, we examined the homology of sex chromosomes in the wide phylogenetic spectrum of lacertids and their outgroups by comparing gene copy numbers between sexes in genes previously found to be Z-specific in some lacertids. Our current sampling covers 45 species from 26 genera including lineages supposed to possess a derived sex determining systems. We found that all tested lacertids share homologous differentiated ZZ/ZW sex chromosomes, which were present already in their common ancestor living around 85 million years ago. These differentiated sex chromosomes are not present in amphisbaenians and teiid lizards, the close relatives of lacertids. Our study demonstrates how inaccuracies in data can influence the outcome of phylogenetic reconstructions of evolution of sex determination, in this case they overestimated the number of shifts from GSD to ESD and the rate in turnovers of sex chromosomes.
- MeSH
- cytogenetika statistika a číselné údaje MeSH
- fylogeneze MeSH
- genotyp * MeSH
- genová dávka MeSH
- ještěři fyziologie MeSH
- molekulární evoluce MeSH
- pohlavní chromozomy genetika MeSH
- procesy určující pohlaví fyziologie MeSH
- sekvenční homologie nukleových kyselin MeSH
- správnost dat MeSH
- vystavení vlivu životního prostředí * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Large-scale untargeted lipidomics experiments involve the measurement of hundreds to thousands of samples. Such data sets are usually acquired on one instrument over days or weeks of analysis time. Such extensive data acquisition processes introduce a variety of systematic errors, including batch differences, longitudinal drifts, or even instrument-to-instrument variation. Technical data variance can obscure the true biological signal and hinder biological discoveries. To combat this issue, we present a novel normalization approach based on using quality control pool samples (QC). This method is called systematic error removal using random forest (SERRF) for eliminating the unwanted systematic variations in large sample sets. We compared SERRF with 15 other commonly used normalization methods using six lipidomics data sets from three large cohort studies (832, 1162, and 2696 samples). SERRF reduced the average technical errors for these data sets to 5% relative standard deviation. We conclude that SERRF outperforms other existing methods and can significantly reduce the unwanted systematic variation, revealing biological variance of interest.
