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Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell "signatures," which were well conserved across data sets. We validated that the relative expression of top cell type markers are associated with proxies for cell type proportions in bulk RNA expression data from postmortem human brain samples. We further validated novel marker genes using an orthogonal ATAC-seq dataset. We performed multiscale coexpression network analysis of the single cell data sets and identified robust cell-specific gene modules. To facilitate the use of the cell type-specific genes for cell type proportion estimation and deconvolution from bulk brain gene expression data, we developed an R package, BRETIGEA. In summary, we identified a set of novel brain cell consensus signatures and robust networks from the integration of multiple datasets and therefore transcend limitations related to technical issues characteristic of each individual study.

In West Africa, weeds are major production constraints in rain-fed lowland rice systems — often located in the inland valleys. Weed management technologies have been developed and promoted in such rice systems, but adoption by farmers lags behind, probably because of insufficient considerations of the system diversity or the farm-specific characteristics during technology development or promotion. This study aimed to identify farm-type specific entry points for innovations in weed management practices of smallholders in rice-based systems in inland valleys. We conducted farm surveys in the Mono Couffo region of Benin in 66 fields in 2010 and 2011 in a range of socio-economic settings typical for smallholder farms. A combination of multivariate analyses using Principal Component Analysis and Agglomerative Hierarchical Cluster is helpful in constructing farm typologies. This categorization, in turn, enables the assessment of farm-type specific weed management strategies and consequently the identification of entry points for innovation. Specific entry points for innovations in weed management include: (i) complementing the existing range of curative options by more preventive measures, (ii) diversifying the existing range of curative measures (mainly hand weeding and herbicide application) by measures that are both non-chemical and labor-saving, and (iii) improving women farmers’ access to information and inputs by targeted training endeavors and conducive credit systems.

Context.— ABO mistransfusions are rare and potentially fatal events. Protocols are required by regulatory agencies to minimize this risk to patients, but how these are applied in the context of massive transfusion protocols (MTPs) is not specifically defined. Objective.— To evaluate the approaches used by transfusion services for switching from universally compatible to patient ABO type-specific blood components during massive hemorrhage. Design.— We added 1 supplemental multiple-choice question to address the study objective to the 2019 College of American Pathologists proficiency test J-survey (J-A 2019). We also reviewed the available literature regarding this topic. Results.— A total of 881 laboratories responded to the supplemental question. Approximately 80% (704 of 881) reported a policy for ABO-type switching during an MTP. Policies varied considerably between responding laboratories, but most (384 of 704, 55%) required 2 ABO types to match before switching from universal to recipient-specific blood components. Additional safety measures used in a minority of these protocols included reaction strength criteria (103 of 704, 15%), on-call medical director approval (41 0f 704, 5.8%), universal red cell unit number limits (12 of 704, 1.7%), or the presence of a mixed field (3 of 704, 0.4%). Conclusions.— This survey reveals that significant heterogeneity exists regarding the available approaches for ABO-type switching during an MTP. Specific expert guidance regarding this issue is very limited, and best practices have not yet been established or rigorously investigated.

O presente artigo tem como objetivo apresentar algumas reflexões sobre a concepção de “afinidades eletivas” e quais seu possível papel na sistematização do processo de racionalização na obra de Max Weber. Trata-se de compreender, em que medida o conceito de afinidades eletivas apresentaria possibilidades analíticas para o esclarecimento do tipo particular de relação, entre as orientações de condutas de vida do protestantismo acético e as formas de organização econômica capitalista, que teria caracterizado o tipo especifico de racionalidade no Ocidente. O estudo tem como foco principal os escritos de Weber sobre a sociologia das religiões, em particular na segunda versão da Die protestantische Ethik und der Geist des Kapitalismus (Ética protestante e espírito do capitalismo) – presente em Gesammelte Aufsätze zur Religionssociologie – (Ensaios reunidos de sociologia da religião) e no estudo - Die Wirtschaftsethik der Weltreligionen (Ética Econômica das religiões mundiais).

Objective This study explored vaccine exemption clustering in Michigan and examined whether vaccine exemptions clustered by exemption type (medical, religious, and philosophical). Furthermore, the study investigated whether Michigan’s nonmedical vaccine exemption policy change had an impact on type-specific vaccine exemption clusters following its implementation. Methods The study used the ArcGIS optimized hot spot analysis tool to visually examine vaccine exemption clustering by type in Michigan. The study analyzed secondary kindergarten vaccine exemption data from 2301 elementary school buildings in Michigan for years spanning 2008 to 2015 and 2016 to 2017 post policy change. Results Clustering of vaccine exemptions by type was present both before and after implementation of the policy with fewer statistically significant features and differences regarding the distribution of hot spot clusters following the policy change. Conclusion Considering the heterogeneity in vaccine exemption hot spot clustering by type can help to inform public health officials to areas/communities at high risk for vaccine preventable disease outbreaks. Such analysis can allow for the implementation of vaccine exemption interventions that are exemption type specific and tailored for a given area, thus maximizing impact and making best use of limited public health resources. This analysis was also able to showcase the impact of Michigan’s nonmedical vaccine exemption policy on vaccine exemption hot spot clusters.

This study aims at exploring gender differences in text-type-specific reading competences via readers’ gender-specific reading preferences. Women were expected to read more often for the sake of entertainment (entertainment preference), whereas men were expected to read more often to gain information (information preference). We further assumed that individuals who read for entertainment would have higher reading competence in fictional literary texts compared with non-fictional informational texts, and vice versa for individuals who read to gain information. The analysis was based on a sample of 830 adults between 19 and 71 years (M = 31.04; SD = 12.53) from a pilot study of the German National Educational Panel Study (NEPS). A structural equation model confirmed that women and men show different reading preferences during leisure time. The preference to read for entertainment was predictive for reading competence in literary texts; however, the preference to read for information had positive effects on reading competence in both informational and literary texts.

Extracting information from large biological datasets is a challenging task, due to the large data size, high-dimensionality, noise, and errors in the data. Gene expression data contains information about which gene products have been formed by a cell, thus representing which genes have been read to activate a particular biological process. Understanding which of these gene products can be related to which processes can for example give insights about how diseases evolve and might give hints about how to fight them. The Next Generation RNA-sequencing method emerged over a decade ago and is nowadays state-of-the-art in the field of gene expression analyses. However, analyzing these large, complex datasets is still a challenging task. Many of the existing methods do not take into account the underlying structure of the data. In this paper, we present a new approach for RNA-sequencing data analysis based on dictionary learning. Dictionary learning is a sparsity enforcing method that has widely been used in many fields, such as image processing, pattern classification, signal denoising and more. We show how for RNA-sequencing data, the atoms in the dictionary matrix can be interpreted as modules of genes that either capture patterns specific to different types, or else represent modules that are reused across different scenarios. We evaluate our approach on four large datasets with samples from multiple types. A Gene Ontology term analysis, which is a standard tool indicated to help understanding the functions of genes, shows that the found gene-sets are in agreement with the biological context of the sample types. Further, we find that the sparse representations of samples using the dictionary can be used to identify type-specific differences.

The molecular pathogenesis of human amyloidosis has been elucidated greatly during the last 20 years. Based on the understanding of the molecular mechanisms of amyloid fibril formation and deposition, various kinds of new drugs and therapeutics have been emerging to improve the prognosis of amyloidosis and even cure this disease. In this review article, we first summarize the pathogenesis and state-of-the-art therapeutics of representative types of systemic human amyloidosis, that is, immunoglobulin light chain-related, transthyretin-related, amyloid A-associated and β2 -microglobulin-related amyloidosis. Next, we describe the essential roles of pathological diagnosis, especially the typing diagnosis of amyloidosis to appropriately guide type-specific therapies of amyloidosis patients. Finally, we introduce the activities of the government-funded group for surveys and research of amyloidosis in Japan, especially the nation-wide pathology consultation system of amyloidosis, which started in April 2018. The nation-wide improvement of the typing diagnosis of amyloidosis is essential for the appropriate treatment and care of amyloidosis patients in Japan.

We study the effect of how types are assigned to participants in a signaling-game experiment. The sender has two actions, In and Out, and two types. In one treatment, types are i.i.d. in every period, and senders gather experience with both types. In the other, types are assigned once-and-for-all, and feedback is type specific. The theory of learning in games predicts that the non-Nash but self-confirming equilibrium where some fraction of types play Out can persist in the fixed-type treatment but not when types are i.i.d. Our results confirm that more senders do play Out in the fixed-type treatment. (JEL C92, D82, D83)

BACKGROUND The scarcity of updated data on the prevalence of cervical human papillomavirus (HPV) infection in the Gulf Cooperation Council (GCC) countries hampers the establishment of cervical cancer screening and HPV vaccination programs. The current study estimated the prevalence of cervical high-risk (HR) HPV infection among women residing in some countries of the GCC and analyzed the correlation between HR-HPV infection types and cytology results. METHODS In total, 2478 women residing in the Kingdom of Saudi Arabia, Qatar, the United Arab Emirates, and Bahrain were enrolled in this study. Cervical specimens were subjected to simultaneous liquid-based cytology and HR-HPV DNA analysis. RESULTS Of 2478 women, 520 (21%) tested positive for HR-HPV. Other non-HPV genotype 16 (HPV16)/HPV18 HR-HPV was the most frequently detected infection type, accounting for 63.7%. Non-Arab women had a significantly higher HR-HPV positivity rate compared with Arab women (31.6% vs 16.4%; P

MotivationAccurate predictions of protein-binding residues (PBRs) enhances understanding of molecular-level rules governing protein–protein interactions, helps protein–protein docking and facilitates annotation of protein functions. Recent studies show that current sequence-based predictors of PBRs severely cross-predict residues that interact with other types of protein partners (e.g. RNA and DNA) as PBRs. Moreover, these methods are relatively slow, prohibiting genome-scale use.ResultsWe propose a novel, accurate and fast sequence-based predictor of PBRs that minimizes the cross-predictions. Our SCRIBER (SeleCtive pRoteIn-Binding rEsidue pRedictor) method takes advantage of three innovations: comprehensive dataset that covers multiple types of binding residues, novel types of inputs that are relevant to the prediction of PBRs, and an architecture that is tailored to reduce the cross-predictions. The dataset includes complete protein chains and offers improved coverage of binding annotations that are transferred from multiple protein–protein complexes. We utilize innovative two-layer architecture where the first layer generates a prediction of protein-binding, RNA-binding, DNA-binding and small ligand-binding residues. The second layer re-predicts PBRs by reducing overlap between PBRs and the other types of binding residues produced in the first layer. Empirical tests on an independent test dataset reveal that SCRIBER significantly outperforms current predictors and that all three innovations contribute to its high predictive performance. SCRIBER reduces cross-predictions by between 41% and 69% and our conservative estimates show that it is at least 3 times faster. We provide putative PBRs produced by SCRIBER for the entire human proteome and use these results to hypothesize that about 14% of currently known human protein domains bind proteins.Availability and implementationSCRIBER webserver is available at http://biomine.cs.vcu.edu/servers/SCRIBER/.Supplementary informationSupplementary data are available at Bioinformatics online.

Using a mouse model of conditional and inducible in vivo fluorescent myonuclear labeling (HSA-GFP), sorting purification of nuclei, low-input reduced representation bisulfite sequencing (RRBS), and a translatable and reversible model of exercise (progressive weighted wheel running, PoWeR), we provide the first nucleus type-specific epigenetic information on skeletal muscle adaptation and detraining. Adult (>4 mo) HSA-GFP mice performed PoWeR for 8 wk then detrained for 12 wk; age-matched untrained mice were used to control for the long duration of the study. Myonuclei and interstitial nuclei from plantaris muscles were isolated for RRBS. Relative to untrained, PoWeR caused similar myonuclear CpG hypo- and hyper-methylation of promoter regions and substantial hypomethylation in interstitial nuclear promoters. Over-representation analysis of promoters revealed a larger number of hyper- versus hypo-methylated pathways in both nuclear populations after training and evidence for reciprocal regulation of methylation between nucleus types, with hypomethylation of promoter regions in Wnt signaling-related genes in myonuclei and hypermethylation in interstitial nuclei. After 12 wk of detraining, promoter CpGs in documented muscle remodeling-associated genes and pathways that were differentially methylated immediately after PoWeR were persistently differentially methylated in myonuclei, along with long-term promoter hypomethylation in interstitial nuclei. No enduring gene expression changes in muscle tissue were observed using RNA-sequencing. Upon 4 wk of retraining, mice that trained previously grew more at the whole muscle and fiber type-specific cellular level than training naïve mice, with no difference in myonuclear number. Muscle nuclei have a methylation epi-memory of prior training that may augment muscle adaptability to retraining., Graphical Abstract Graphical Abstract

Efforts to elucidate protein–DNA interactions at the molecular level rely in part on accurate predictions of DNA-binding residues in protein sequences. While there are over a dozen computational predictors of the DNA-binding residues, they are DNA-type agnostic and significantly cross-predict residues that interact with other ligands as DNA binding. We leverage a custom-designed machine learning architecture to introduce DNAgenie, first-of-its-kind predictor of residues that interact with A-DNA, B-DNA and single-stranded DNA. DNAgenie uses a comprehensive physiochemical profile extracted from an input protein sequence and implements a two-step refinement process to provide accurate predictions and to minimize the cross-predictions. Comparative tests on an independent test dataset demonstrate that DNAgenie outperforms the current methods that we adapt to predict residue-level interactions with the three DNA types. Further analysis finds that the use of the second (refinement) step leads to a substantial reduction in the cross predictions. Empirical tests show that DNAgenie’s outputs that are converted to coarse-grained protein-level predictions compare favorably against recent tools that predict which DNA-binding proteins interact with double-stranded versus single-stranded DNAs. Moreover, predictions from the sequences of the whole human proteome reveal that the results produced by DNAgenie substantially overlap with the known DNA-binding proteins while also including promising leads for several hundred previously unknown putative DNA binders. These results suggest that DNAgenie is a valuable tool for the sequence-based characterization of protein functions. The DNAgenie’s webserver is available at http://biomine.cs.vcu.edu/servers/DNAgenie/.

Due to various external influencing factors as well as different planning and operating principles of system operators, there is a multitude of distribution grid structures in the electrical energy system. This leads to a more difficult reproducibility of system analysis results, which is especially hindering in energy research. In order to improve the reproducibility of results in the future, this paper presents an overview of key indicators that can be used to classify electrical grids and describe their characteristics. This should ensure that, e.g., only grids with similar properties are compared with each other with regard to their results from grid analyses. Furthermore, it shall enable grid type specific evaluations of analysis results, e.g. if a special control algorithm performs better in one grid category than in another. Among other uses, these evaluations can also be beneficial for specific network regulation issues.

BackgroundThere are >200 protein post-translational modification (PTMs) types described in eukaryotes, having diverse species conservation levels, proteome coverage, number of high-throughput experiments and functional roles. From a clinical perspective, a number of diseases have been associated to deregulated PTM sites and missense rare variants are globally enriched in PTMs. We hypothesize that some genetic diseases may be caused by the deregulation of particular functions produced by the removal of a specific PTM type by genomic variants.ResultsWe collected >320,000 human PTMs of 59 types and cross them with >4M missense DNA variants annotated with pathogenic predictions and disease associations. We report >1.74M PTM-variant concurrences in >16,500 proteins that an enrichment analysis distributed in 217 pairwise significant associations between 18 PTM types and 150 genetic diseases. Around 23% of these associations are already described in the literature, 34% have partial evidences based on single variants, related diseases or regulatory evidences, and 43% are novel. Removal of acetylation presents the highest effect, still low studied PTM types like S-glutathionylation or S-nitrosylation show relevance. A network of PTM types and phenotypes associations is also discussed. Using pathogenicity predictions we identified potential PTM sites to produce particular diseases if genomic variants remove them.ConclusionsOur results show an important impact of PTM removal producing genetic diseases and phenotypes that is PTM type specific. We describe for the first time a general scenario of PTM types and genetic diseases direct associations, many of them novel, that provides new capacities to understand and diagnose these disorders.

Background Persistent infection with high-risk human papillomavirus (hrHPV) is a critical step in cervical carcinogenesis. We report on type-specific hrHPV persistence, clearance and incidence among screen-positive Rwandan women living with HIV (WLWH). Methods This was a nested analysis from a large cervical cancer screening study of ~ 5000 Rwandan WLWH. Women who tested positive for hrHPV and/or visual inspection with acetic acid were referred to colposcopy. For a subset of women (n = 298) who were ≥ 6 months delayed in receiving colposcopy, we tested their screening and colposcopy visit specimens using the AmpFire HPV genotyping assay that tests 14 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) individually. Results The mean, median (interquartile range [IQR]) and range of time between the screening and colposcopy visits were 644, 650 (490–820.5) and 197–1161 days, respectively. Mean, median (IQR) and range of age at the screening visit were 38, 37 (34–43) and 30–54 years, respectively. Two-hundred eighty-three (95.0%) had CD4 count (cells per mm3) data available at baseline with mean, median (IQR) and range of 592, 513 (346–717) and 0–7290, respectively. Two-hundred thirty-five WLWH were positive for at least one hrHPV type at the screening visit, of whom 50.2% had at least one HPV type-specific infection persist; 37.2% of all HPV infections detected at the screening visit persisted. Compared to all other HPV types in aggregate, HPV16 (vs. non-HPV16 types) (47.7%, p = 0.03) and HPV33 (vs. non-HPV33 types) (56.7%, p = 0.03) were significantly more likely, and HPV39 (vs. non-HPV39 types) (6.7%, p = 0.01), HPV51 (vs. non-HPV51 types) (15.6%, p p = 0.04) were significantly less likely, to persist. Lower CD4 counts were associated with having any persistent hrHPV infection (ptrend = 0.04) and multiple persistent hrHPV infections (ptrend = 0.04). Conclusion There is a significant proportion of WLWH with persistent hrHPV infection, emphasizing the need to vaccinate them against HPV prior to becoming sexually active.

Using a mouse model of conditional and inducible in vivo fluorescent myonuclear labeling (HSA-GFP), sorting purification of nuclei, low-input reduced representation bisulfite sequencing (RRBS), and a translatable and reversible model of exercise (progressive weighted wheel running, PoWeR), we provide the first nucleus type-specific epigenetic information on skeletal muscle adaptation and detraining. Adult (>4 mo) HSA-GFP mice performed PoWeR for 8 wk then detrained for 12 wk; age-matched untrained mice were used to control for the long duration of the study. Myonuclei and interstitial nuclei from plantaris muscles were isolated for RRBS. Relative to untrained, PoWeR caused similar myonuclear CpG hypo- and hyper-methylation of promoter regions and substantial hypomethylation in interstitial nuclear promoters. Over-representation analysis of promoters revealed a larger number of hyper- versus hypo-methylated pathways in both nuclear populations after training and evidence for reciprocal regulation of methylation between nucleus types, with hypomethylation of promoter regions in Wnt signaling-related genes in myonuclei and hypermethylation in interstitial nuclei. After 12 wk of detraining, promoter CpGs in documented muscle remodeling-associated genes and pathways that were differentially methylated immediately after PoWeR were persistently differentially methylated in myonuclei, along with long-term promoter hypomethylation in interstitial nuclei. No enduring gene expression changes in muscle tissue were observed using RNA-sequencing. Upon 4 wk of retraining, mice that trained previously grew more at the whole muscle and fiber type-specific cellular level than training naïve mice, with no difference in myonuclear number. Muscle nuclei have a methylation epi-memory of prior training that may augment muscle adaptability to retraining.

Current methods in comparative genomic analyses for metabolic potential prediction of proteins involved in, or associated with the Dsr (dissimilatory sulphite reductase)-dependent dissimilatory sulphur metabolism are both time-intensive and computationally challenging, especially when considering metagenomic data. We developed DiSCo, a Dsr-dependent dissimilatory sulphur metabolism classification tool, which automatically identifies and classifies the protein type from sequence data. It takes user-supplied protein sequences and lists the identified proteins and their classification in terms of protein family and predicted type. It can also extract the sequence data from user-input to serve as basis for additional downstream analyses. DiSCo provides the metabolic functional prediction of proteins involved in Dsr-dependent dissimilatory sulphur metabolism with high levels of accuracy in a fast manner. We ran DiSCo against a dataset composed of over 190 thousand (meta)genomic records and efficiently mapped Dsr-dependent dissimilatory sulphur proteins in 1798 lineages across both prokaryotic domains. This allowed the identification of new micro-organisms belonging to Thaumarchaeota and Spirochaetes lineages with the metabolic potential to use the Dsr-pathway for energy conservation. DiSCo is implemented in Perl 5 and freely available under the GNU GPLv3 at https://github.com/Genome-Evolution-and-Ecology-Group-GEEG/DiSCo.

Thioredoxins (TRXs) are ubiquitous disulfide oxidoreductases structured according to a highly conserved fold. TRXs are involved in a myriad of different processes through a common chemical mechanism. Plant thioredoxins evolved into seven types with diverse subcellular localization and distinct protein targets selectivity. Five TRX types coexist in the chloroplast, with yet scarcely described specificities. We solved the first crystal structure of a chloroplastic z-type TRX, revealing a conserved TRX fold with an original electrostatic surface potential surrounding the redox site. This recognition surface is distinct from all other known TRX types from plant and non-plant sources and is exclusively conserved in plant z-type TRXs. We show that this electronegative surface endows TRXz with a capacity to activate the photosynthetic Calvin-Benson cycle enzyme phosphoribulokinase. TRXz distinct electronegative surface thereby extends the repertoire of TRX-target recognitions.

Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF10-DEIA-LiPA25 (SPF10 method) has reduced sensitivity towards HPV-45 and -59. Therefore, anogenital samples from the PASSYON study were retrospectively analyzed with type-specific (TS) HPV-45 and -59 qPCR assays. The SPF10 method missed 51.1% of HPV-45 and 76.1% of HPV-59 infections, detected by the TS qPCR assays. Viral copy number (VCn) of SPF10 missed HPV-45 and -59 was significantly lower than SPF10 detected HPV-45 and -59 (p

MicroRNAs are used as biomarkers for classification of cancer subtypes since certain miRNAs are differentially expressed in normal and patient samples. Moreover, miRNAs target mRNAs and can heavily influence Gene Expressions. Thus, deregulation of miRNAs is linked to various disorders. Thus, miRNAs can be used for prognosis and developing personalized health solutions for patients. Given the importance of miRNAs, there has been substantial work done in the field. In this paper, recent works in the field of using miRNAs expressions of patients were considered. A total of 20 papers were surveyed which utilized feature selection ensembles, fuzzy logic as well as deep learning. 10 papers have been reported which offer insight into how miRNAs can be utilized for subtype-specific or generalized cancer diagnosis.

In context of the ongoing multi-centric HPV vaccine study in India, unvaccinated married women (N = 1484) aged 18–23 years were recruited in 2012–2015 as age-matched controls to the vaccinated women and followed up yearly. We assess type-specific prevalence, natural history and potential determinants of human papillomavirus (HPV) infection in these unvaccinated women. Cervical samples were collected yearly for at least four consecutive years. A Multiplex Type-Specific E7-Based polymerase chain reaction assay was used to detect 21 HPV types. HPV prevalence was 36.4% during 6 years. Most common HPV types were 16 (6.5%) and 31 (6.1%). Highest persistence were observed for HPV 35 (62.5%) and 52 (25%). New HPV acquisition rate was 5.6/1000 person-months of observation (PMO), highest for HPV 16 (1.1/1000 PMO). Type-specific clearance rates ranged between 2.9–5.5/100 PMO. HPV 16 and/or 18 infections were 41% (95% CI 4–63%) lower among women with 2

Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12&ndash, 16 years who were born in 1994 or later. The rate of OHPV coverage was 70&ndash, 80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We aim to investigate the change in prevalence of HPV infection after the initiation of HPV vaccination. We recruited females aged 20&ndash, 21 years attending public cervical cancer screening from 2014 to 2017 fiscal years (April 2014 to March 2018). Residual Pap test specimens were collected for HPV testing. We compared the prevalence of HPV type-specific infection between women registered in 2014 (born in 1993&ndash, 1994, including the pre-OHPV generation) and registered in 2015&ndash, 2017 (born in 1994&ndash, 1997, the OHPV generation). We collected 2379 specimens. The vaccination coverage figures were 30.7%, 86.6%, 88.4% and 93.7% (p &lt, 0.01) from 2014 to 2017, respectively. The prevalence of HPV16/18 infection significantly decreased from 1.3% in 2014 to 0% in 2017 (p = 0.02). The three most prevalent types were HPV52, 16 and 56 in 2014, and HPV52, 58 and 56 in 2015&ndash, 2017, respectively. HPV16 and 33 infection rates decreased. On the other hand, the HPV58 infection rate was obviously increased after OHPV from 0.3% to 2.1%. Our study demonstrates that the prevalence of HPV16/18 infection dramatically decreased and the profile of type-specific HPV infection was changed after OHPV.

The recently identified pathogenic Porcine circovirus type 3 (PCV3) may threaten to reduce the pig population dramatically worldwide. In our previous study, a PCV3-specific monoclonal antibody (mAb-1H11) was successfully applied in immune-histochemistry staining and ELISA, which specifically recognize PCV3 capsid protein in PCV3-positive pig tissues. In the present study, we expressed and purified the soluble sole capsid protein of PCV3. The purified capsid protein was capable of self-assembly into virus-like-particles (VLPs), which is validated by transmission electron microscopy and dynamic light scattering assays. Moreover, the epitope of mAb-1H11 was identified in the CD-loop region (a.a. 72-79) on the VLP surface, which is confirmed by PCV2-PCV3 epitope swapping assay. For the first time, we determined the cryo-EM structure of PCV3-VLP at 8.5 Å resolution that reveals the detailed structural information of PCV3-VLP. In our cryo-EM structure, PCV3-VLP is composed of 60 capsid protein subunits assembled with T = 1 icosahedral symmetry. Consistent to our bio-dot Western blot assay, the structural comparison between PCV3 and PCV2 revealed significant structural differences in the surface-exposed loops, including the CD-loop (a.a. 72-79) and the EF-loop (a.a. 109-131). Our work provides a structural framework for engineering future PCV3 vaccine and diagnosis kits development.

Magnetic nanoparticles (MNP) have been successfully used as additives for the fabrication of implants such as hernia implants or vascular grafts in order to enable their in-vivo visualization with magnetic resonance imaging (MRI). However, functionality and long term stability of such implants were not quantitatively assessed until now. Reliable assessment of functionality is related not only to the determination of MNP concentration, but also to the impact of aggregation and immobilization of MNP inside the implant material on the MRI signal. In this regard, novel models must be developed which describe the relation between proton relaxation and both MNP clustering and mobility of MNP inside the implants. In this study, we experimentally quantify the transverse relaxation dependence on MNP size and MNP clusters, confirming theoretical descriptions. We identify three MNP size ranges for which different proton relaxation trends occur: One for which relaxivity increases with size (up to approx. 75 nm), a second for which relaxivity is constant (from 75 nm to 130 nm) and a third for which relaxivity decreases (from 130 nm to 220 nm). Further, we describe the impact of gradual MNP immobilization in agarose gels on relaxivity for three MNP types representing either of the identified size ranges. For all MNP types, we observe an increase of relaxivity with agarose content up to an MNP type specific maximum value. The relative rise of relaxivity is higher for MNP with larger sizes. The highest increase of the transverse relaxivity from 240 mM-1s−1 to 1000 mM-1 s−1 is achieved for MNP clusters after immobilization in a gel with 7%(w/w) agarose. The effects of MNP clustering and immobilization on relaxivity are valuable information for the engineering of implants with different contrast properties in MRI. Further, the relation between MNP immobilization and relaxivity values may serve as a basis for future non-invasive assessment of changes in implant functionality by MRI measurements.

This study investigated the chemodiversity and unique signatures for dissolved organic matter (DOM) from different types of water using high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Eight freshwater hydrophobic DOM (HPO) share 10-17% formulas that were mainly lignin-like compounds. Unique signatures were synthesized: unique to the high-humic HPO (Suwannee River and Blavet River) were condensed aromatic and some aliphatic compounds with H/C 1.5 and O/C 0.2, which is considered as decisive of these black river water. Medium-humic isolates (Loire River, Seine River, South Platte River, and Ribou Dam) did not show explicit unique signatures. Nonetheless, enhanced chemodiversity was observed for medium-humic isolates extracted from a variety of indigenous environmental conditions. As an example, South Platte River HPO isolated in winter showed signatures similar to low-humic HPO (Colorado River), i.e., predominantly aliphatic CHO (H/C 1.0). Effluent HPO was mainly aliphatic molecules with 0.2 O/C 0.5 and enriched in S-bearing molecules, and molecules unique to glacial DOM (Pony Lake) incorporated N-bearing compounds that were inferiorly oxidized and were considered as microbial-derived. The weight-averaged double bond equivalent and elemental ratio derived from FTICR-MS were compared with SUVA

Reflective supertype information (RSI) is useful for many instrumentation-based type-specific analyses on the Java Virtual Machine (JVM). On the one hand, while such information can be obtained when performing the instrumentation within the same JVM process executing the instrumented program, in-process instrumentation severely limits the bytecode coverage of the analysis. On the other hand, performing the instrumentation in a separate process can achieve full bytecode coverage, but complete RSI is generally not available, often requiring the insertion of expensive runtime type checks in the instrumented program. In this article, we present a novel technique to accurately reify complete RSI in a separate instrumentation process. This is challenging, because the observed application may make use of custom classloaders and the loaded classes in one application execution are generally only known upon termination of the application. We implement our technique in an extension of the dynamic analysis framework DiSL. The resulting framework guarantees full bytecode coverage, while providing RSI. Evaluation results on a task profiler demonstrate that our technique can achieve speedups up to a factor of 6.24× wrt. resorting to runtime type checks in the instrumentation code for an analysis with full bytecode coverage.

Accurate and efficient computation of protein-protein binding free energy remains a grand challenge. In this study, we develop a new strategy to achieve efficient calculation for total protein-protein binding free energies with improved accuracy. The new method combines the recently developed interaction entropy method for efficient computation of entropic change together with the use of residue type-specific dielectric constants in the framework of MM/GBSA to achieve optimal result for protein-protein binding free energies. The new strategy is shown to be computationally efficient and accurate than that using standard MM/GBSA methods in which the entropic computation is performed by the normal model approach and the protein interior is represented by the standard dielectric constant (typically set to 1), both in terms of accuracy and computational efficiency. Our study using the new strategy on a set of randomly selected 20 protein-protein binding systems produced an optimal dielectric constant of 2.7 for charged residues and 1.1 for noncharged residues. Using this new strategy, the mean absolute error in computed binding free energies for these 20 selected protein-protein systems is significantly reduced by more than 3-fold while the computational cost is reduced by more than 2 orders of magnitude, compared to the result using standard MM/GBSA method with the normal mode approach. A similar improvement in accuracy is confirmed for a test set consisting of 10 protein-protein systems.

Background Comparing gene expression profiles using gene expression datasets of different types of tumors is frequently used to identify molecular mechanisms of cancer. This study aimed to find shared and type specific gene expression profiles of hepatocellular carcinoma (HCC) and B-cell chronic lymphocytic leukemia (B-CLL). Material and methods Gene expression microarrays for HCC and B-CLL and RNA-sequencing expression data for liver HCC and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) were analyzed and differentially expressed probe sets or genes for each cancer type were detected. Probe sets and genes that were shared or specifically expressed in both cancer types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms for Biological Process (BP) annotations were performed. Results According to our analysis shared upregulated genes were mainly annotated in cell cycle processes. Some of the genes that changed only in HCC were annotated in cell cycle and metabolic processes, and some of the genes, altered only in B-CLL, were annotated in immune response and hemopoiesis. Conclusion These results contribute to cancer research that aim to find the conserved gene expression profiles in different cancer types and widen the knowledge of HCC and B-CLL specific mechanisms.

Background The number of diagnostic assays for the detection of herpes simplex virus type 1 (HSV-1) antibodies has increased over the years. However, their performance characteristics could vary among global populations. Objective To investigate performance of two commercial ELISA kits, HerpeSelect® 1 ELISA and Euroimmun Anti-HSV-1 (gC1) ELISA (IgG); and two commercial immunoblot (IB)/Western blot (WB) assays, HerpeSelect® 1 and 2 Immunoblot IgG, and Euroimmun Anti-HSV-1/HSV-2 gG2 Euroline-WB (IgG/IgM); in detecting HSV-1 antibodies in a Middle East and North Africa (MENA) population. Study design Blood specimens were collected from blood donors in Doha, Qatar, June 2013–2016. Twenty specimens were randomly selected from 10 MENA nationalities (Egypt, Iran, Jordan, Lebanon, Pakistan, Palestine, Qatar, Sudan, Syria, and Yemen; total = 200), and tested for HSV-1 antibodies. Results Across all six comparisons between assays, positive percent agreement ranged between 95.7% (95% CI: 91.4–98.3%) and 100.0% (95% CI: 97.8–100.0%). Negative percent agreement ranged between 86.2% (95% CI: 68.3-96.1%) and 96.2% (95% CI: 80.4–99.9%). Overall percent agreement ranged between 95.7% (95% CI: 91.7–97.8%) and 99.4% (95% CI: 96.7–99.9%). Cohen’s kappa statistic ranged between 0.84 (95% CI: 0.73–0.95) and 0.98 (95% CI: 0.93–1.00). Compared against IB/WB, HerpeSelect® and Euroimmun had sensitivities and specificities >96% and >86%, respectively. Positive and negative predictive values were >97% and >83%, respectively. Conclusion The assays showed excellent concordance with one another, and with a high kappa statistic. The ELISA kits demonstrated robust diagnostic performance compared to the IB/WB assays. These findings support the assays’ utility in clinical diagnosis and research in MENA populations.

Background: Viruses of the Herpes viridae family infect 90% of the Earth’s population. Humans are the hosts of at least nine unique herpes viruses. Aim: This study is aimed at evaluating the seroprevalence of type specific herpes simplex virus infection and the associated risk factors in a cross-section of asymptomatic healthy women of childbearing age in Kogi state, Nigeria. Methodology: A total of 330 females of child bearing age (15 - 49 years) participated in this study. They were recruited from various local government areas of three Senatorial districts of Kogi state. Blood samples were collected from participants and analyzed for HSV-1 and HSV-2 antibodies (IgG) quantitatively with ELISA kit. Results: The overall prevalence of HSV was 76.7%. Data further show that majority (96.4%) of the population studied had HSV-1, while 77% had HSV-2 infections. Results also showed that the young adults indicated prevalence of 95.7% for HSV-1 and 74.7% for HSV-2, while in the middle aged, the prevalence were 98.6% for HSV-1, and 84.9% for HSV-2. 99.2% of the married women were positive for HSV-1, while 86.9% were positive for HSV-2. 94.5% of the unmarried women were positive for HSV-1, while 70.5% were positive for HSV-2. The risk of HVS-1 or VS-2 infections was not associated with age, age of first sexual exposure and number sex partners before marriage. Married women were at greater risk for HSV-1 (p = 0.03) and HSV-2 (p ≤ 0.001) infections compared to the unmarried women. Conclusion: The prevalence of the HSV-1 and HSV-2 infections was high among asymptomatic healthy women of childbearing age in Kogi state, Nigeria. Efforts should be made to increase the awareness of HSV infection among the child bearing populace.

SenseWear Mini Armband, an accelerometer with multiple physiological sensors, could be a practical means to estimate energy expenditure (EE) of children and adolescents, but its validity reported for these age groups has not been consistent within the literature. EE of twenty-six healthy Chinese 12-year-old adolescents was measured simultaneously using both SenseWear Mini Armband (SWMA) and metabolic chamber (MC) during a 16-hour stay in a MC. SWMA systematically underestimated the adolescents’ EE during sedentary behaviors, resting metabolic rate (RMR), basal metabolic rate (BMR), and total EE, with the absolute error rate ranging from 14.85% to 28.65%. The SWMA significantly underestimated EE compared with MC in Chinese adolescents. However, the amount of error can be reduced by applying correction equation proposed in this study. Key words: sitting, physical inactivity, accelerometer, activity monitor, whole-room calorimetry

The regionalisation of flood frequencies is a precondition for the estimation of flood statistics for ungauged basins. It is often based on either the concept of hydrological similarity of catchments or spatial proximity. Similarity is usually defined by comparing catchment attributes or distances. Here, we apply flood types in regionalisation directly to consider the type-specific aspects of similarity. The different flood types are classified according to their meteorological causes and hydrographs. Their probability distributions are modelled by type-specific distribution functions which are combined into one statistical annual mixture model afterwards. For regionalisation, we specified the parameters of each type-specific probability distribution separately with hierarchical clustering and regressions from catchment attributes. By selection of most relevant features, depending on the flood type, the specifics of flood-generating processes and meteorological causes were considered. The results demonstrate how this consideration of deterministic aspects can improve the transferability of distribution parameters to ungauged catchments. The type-specific regionalisation approach offers a higher degree of freedom for regionalisation as it describes the relationships between catchment characteristics, meteorological causes of floods and response of watersheds.

Grassland soils represent a significant potential pool for the sequestering of atmospheric CO2; however, the magnitude of this pool depends to a certain extent on the grazing management of the grassland. Whether different herbivore species and combinations (herbivore assemblage) influence the soil organic carbon (SOC) in various grasslands remains unclear. Here we have investigated the impacts of herbivore assemblages (NG, no grazing; SG, sheep grazing; CG, cattle grazing; and MG, mixed grazing of sheep and cattle) under moderate grazing intensity on a shallow layer of SOC storage across the three different grassland types (meadow steppe, typical steppe, and desert steppe) in the temperate steppes of Eastern Eurasia. We found that herbivore-species-specific effects on SOC storage depended on the grassland type. In mesic grasslands (i.e. meadow steppe and typical steppe), CG enhanced SOC storage, but there were no effects from SG. In contrast, SG in the xeric grassland (i.e. desert steppe) dramatically increased SOC storage while no effects were observed for CG. Importantly, MG of sheep and cattle consistently increased SOC storage across all grassland types. We suggest that adopting herbivore-type-specific stewardship in different grasslands could assist with the enhancement of ecosystem C functionality and services; large herbivores and small herbivores are suitable for grazing in mesic grasslands and xeric grasslands, respectively. Moreover, MG with diverse herbivores may be the optimal moderate grazing mode for soil C sequestration in most grasslands of northern China.

Summary Objectives Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. Methods We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18–64 and 65 years and above) using random-effects models. Results We identified 3411 publications and 30 met our inclusion criteria. Between 2010–11 and 2014–15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18–64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. Conclusions Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.

Highlights • Silent circulation (SC) of wild polio viruses (WPV) when oral polio vaccine (OPV) use is stopped, could threaten eradication. • We analyzed a model designed to develop theory about mechanisms and factors that lead to SC and how SC risks can be assessed using surveillance data. • Prolonged low-level SC emerges as a threshold phenomenon through a mechanism related to balancing contributions of different populations to the effective reproduction number. • Factors that promote this mechanism are many years of inadequate vaccination efforts, ongoing waning of immunity against transmission years after last OPV or WPV infection, low transmissibility of OPV, and high transmission conditions. • Analyzing acute flaccid paralysis surveillance or environmental surveillance data by themselves cannot assess the risk that an SC threshold has been passed, but new methods to analyze them jointly could do so., Waning immunity could allow transmission of polioviruses without causing poliomyelitis by promoting silent circulation (SC). Undetected SC when oral polio vaccine (OPV) use is stopped could cause difficult to control epidemics. Little is known about waning. To develop theory about what generates SC, we modeled a range of waning patterns. We varied both OPV and wild polio virus (WPV) transmissibility, the time from beginning vaccination to reaching low polio levels, and the infection to paralysis ratio (IPR). There was longer SC when waning continued over time rather than stopping after a few years, when WPV transmissibility was higher or OPV transmissibility was lower, and when the IPR was higher. These interacted in a way that makes recent emergence of prolonged SC a possibility. As the time to reach low infection levels increased, vaccine rates needed to eliminate polio increased and a threshold was passed where prolonged low-level SC emerged. These phenomena were caused by increased contributions to the force of infection from reinfections. The resulting SC occurs at low levels that would be difficult to detect using environmental surveillance. For all waning patterns, modest levels of vaccination of adults shortened SC. Previous modeling studies may have missed these phenomena because (1) they used models with no or very short duration waning and (2) they fit models to paralytic polio case counts. Our analyses show that polio case counts cannot predict SC because nearly identical polio case count patterns can be generated by a range of waning patterns that generate different patterns of SC. We conclude that the possibility of prolonged SC is real but unquantified, that vaccinating modest fractions of adults could reduce SC risk, and that joint analysis of acute flaccid paralysis and environmental surveillance data can help assess SC risks and ensure low risks before stopping OPV.

Background Stroke has become the leading cause of death in China. This study aimed to assess the age-period-cohort (APC) effects on the long-term trends of type-specific stroke morbidity and mortality in China between 1993 and 2017.Methods and Results:The data were obtained from the Global Burden of Disease 2017 (GBD 2017) and were analyzed with the age-period-cohort framework. The net drifts of mortality were below 0 (hemorrhagic stroke [HS]: males: -1.620%, females: -3.531%; ischemic stroke [IS]: males: -1.041%, females: -3.002%), and the local drift values were below 0 in all age groups and for both genders. The net drifts of HS incidence were below 0 (males: -1.412%, females: -2.688%), while those of IS were above 0 (males: 1.425%, females: 1.117%). Period effect of mortality showed similar monotonic downward patterns for both genders, with a faster decrease for females than for males. Period effect of incidence showed a declined trend of incidence for HS, but an elevated trend for IS in both genders. After controlling for age and period effects, cohort effects on incidence found a monotonic decline trend for HS, while for IS, an elevated trend was found at first to peak during the 1950-1970 s, then declined steadily afterwards. Cohort effects on mortality showed a monotonic declined trend. Conclusions By using Age-Period-Cohort (APC) analysis, a disparity between HS and IS was identified. Different prevention and control strategies should be used depending on the subtypes of stroke.

Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions.

Bluetongue (BT) is one of the important viral diseases of domestic and wild ruminants, especially small ruminants such as sheep. Out of the 29 BTV serotypes prevalent in the world, at least 24 of the serotypes are reported in India, either by virus isolation or serology. To better understand the seroprevalence of BTV, we conducted a comprehensive study in the main reservoir hosts of BTV, i.e., cattle and buffaloes of different age groups in Andhra Pradesh and Telangana states of India where the disease is majorly prevalent. A total of 321 blood samples collected from cattle and buffaloes during 2017-2018 were tested for group-specific BTV seroprevalence by c-ELISA, followed by type specific seroprevalence (against BTV-1, 2, 4, 5, 9, 12, 16, and 24) by serum neutralization test. Of the 311 BTV seropositive samples, 112, 98, 102, 127, 2, 113, 160, and 5 samples neutralized BTV-1, 2, 4, 5, 9, 12, 16, and 24, respectively. Twenty-nine samples could not neutralize any of the tested BTV serotypes. Majority of the sera neutralized more than one serotype, up to a maximum of six serotypes. Major finding of the study is detection of BTV serotypes not included in the commercial pentavalent inactivated vaccine. Regular surveillance of circulating serotypes, especially in sentinel reservoir hosts throughout the country can help in designing better multivalent vaccines with suitable vaccine strains, for specific geographic regions.

Disaster management urgently requires mechanisms for achieving situation awareness (SA) in a timely manner, allowing authorities to react in an appropriate way to reduce the impact on affected people and infrastructure. In such situations, no matter if they are human-induced like shootings or natural ones like earthquakes or floods, social media such as Twitter are frequently used communication channels, making them a highly valuable additional data source for enhancing SA. The challenge is, however, to identify out of the tremendous mass of irrelevant and non informative social media data those messages being really “informative”, i.e., contributing to SA in a certain disaster situation. Existing approaches on machine-learning driven informativeness classification most often focus on specific disaster types, such as shootings or floods, thus lacking general applicability and falling short in classification of new disaster events. Therefore, this article puts forward the following three contributions: First, in order to better understand the underlying social media data source, an in-depth analysis of existing Twitter data on 26 different disaster events is provided along temporal, spatial, linguistic, and source dimensions. Second, based thereupon, a cross-domain informativeness classifier is proposed being not focused on specific disaster types but rather allowing for classifications across different types. Third, the applicability of this cross-domain classifier is demonstrated, showing its accuracy compared to other disaster type specific approaches.

Influenza incidence forecasting is used to facilitate better health system planning and could potentially be used to allow at-risk individuals to modify their behavior. For example, the US Centers for Disease Control and Prevention (CDC) runs an annual competition to forecast influenza-like illness (ILI) at the regional and national levels in the US, based on a standard discretized incidence scale. Here, we use a suite of forecasting models to analyze type-specific incidence at the smaller spatial scale of clusters of nearby counties. We used data from point-of-care (POC) diagnostic machines over three seasons, in 10 clusters, capturing: 57 counties; 1,061,891 total specimens; and 173,909 specimens positive for Influenza A. Total specimens were closely correlated with comparable CDC ILI data. Mechanistic models were substantially more accurate when forecasting influenza A positive POC data than total specimen POC data, especially at longer lead times. Also, models that fit individual counties separately were better able to forecast clusters than were models that directly fit to aggregated cluster data. Public health authorities may wish to consider developing forecasting pipelines for type-specific POC data in addition to ILI data. Simple mechanistic models will likely improve forecast accuracy when applied at small spatial scales to pathogen-specific data before being scaled to larger geographical units and broader syndromic data. Highly local forecasts may enable new public health messaging to encourage at-risk individuals to temporarily reduce their social mixing.

Presynaptic homeostatic plasticity (PHP) is an evolutionarily conserved form of adaptive neuromodulation, observed at both central and peripheral synapses. We make several fundamental advances, interrogating the synapse-specificity of presynaptic homeostatic plasticity. We define how PHP remains robust to acute versus long-term neurotransmitter receptor perturbation. We describe a general property of PHP, which includes global induction and synapse-specific expression mechanisms. Finally, we detail a novel synapse-specific expression mechanism for PHP that enables the conversion from short to long-term PHP expression. If our data can be extended to other systems, including the mammalian central nervous system, it suggests that PHP can be broadly induced and expressed to sustain the function of complex neural circuitry.

Objectives Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent. Methods We used nine seasons of comprehensive nationwide surveillance data from Greece (2010–2011 to 2018–2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. Results For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38–2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54–4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons (≥65 vs. 40–64 years, RR for intensive care 5.42, 95% CI 3.45–8.65, and RR for death 6.19, 95%CI 4.05–9.38). Within the 40–64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B. Discussion Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.