On natural metalinguistic abilities in aphasia: a preliminary study

Natural metalinguistic abilities, which are put into play without explicit instructions, constitute the cognitive basis for a 'reflexive' use of language, a particular manifestation of the executive function when applied to language and verbal behaviour. This reflexive use entails a specific attentional activity by speakers and hearers with regard to linguistic outputs, and an intentional experience-based control over the language use. Putting into play natural metalinguistic abilities can be considered a significant factor for explaining different kinds of adaptive processes. Our results permit us to conclude that an impairment of metalinguistic abilities is involved in aphasia to different degrees. Moreover, the examination of preserved metalinguistic abilities provides an alternative way for assessing the degree of severity of impaired communicative behaviour by people with aphasia. Our procedure, presumably, will also be useful for suggesting new factors when designing therapeutic programmes

Towards actionable knowledge: A systematic analysis of mobile patient portal use

As the aging population grows, chronic illness increases, and our healthcare costs sharply increase, patient portals are positioned as a central component of patient engagement through the potential to change the physician-patient relationship and enable chronic disease self-management. A patient’s engagement in their healthcare contributes to improving health outcomes, and information technologies can support health engagement. In this chapter, we extend the existing literature by discovering design gaps for patient portals from a systematic analysis of negative users’ feedback from the actual use of patient portals. Specifically, we adopt a topic modeling approach, latent Dirichlet allocation (LDA) algorithm, to discover design gaps from online low rating user reviews of a common mobile patient portal, EPIC’s mychart. To validate the extracted gaps, we compared the results of LDA analysis with that of human analysis. Overall, the results revealed opportunities to improve collaboration and to enhance the design of portals intended for patient-centered care. Incorporating these changes may enable the technologies to have stronger position to influence health improvement and wellness

DNA Replication Fading As Proliferating Cells Advance in Their Commitment to Terminal Differentiation

Terminal differentiation is the process by which cycling cells stop proliferating to start new specific functions. It involves dramatic changes in chromatin organization as well as gene expression. In the present report we used cell flow cytometry and genome wide DNA combing to investigate DNA replication during murine erythroleukemia-induced terminal cell differentiation. The results obtained indicated that the rate of replication fork movement slows down and the inter-origin distance becomes shorter during the precommitment and commitment periods before cells stop proliferating and accumulate in G1. We propose this is a general feature caused by the progressive heterochromatinization that characterizes terminal cell differentiation

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

BACKGROUND: In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. RESULTS: A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION: Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS

Genomic and biological characterization of chiltepin yellow mosaic virus, a new tymovirus infecting Capsicum annuum var. aviculare in Mexico.

The characterization of viruses infecting wild plants is a key step towards understanding the ecology of plant viruses. In this work, the complete genomic nucleotide sequence of a new tymovirus species infecting chiltepin, the wild ancestor of Capsicum annuum pepper crops, in Mexico was determined, and its host range has been explored. The genome of 6,517 nucleotides has the three open reading frames described for tymoviruses, putatively encoding an RNA-dependent RNA polymerase, a movement protein and a coat protein. The 5′ and 3′ untranslated regions have structures with typical signatures of the tymoviruses. Phylogenetic analyses revealed that this new virus is closely related to the other tymoviruses isolated from solanaceous plants. Its host range is mainly limited to solanaceous species, which notably include cultivated Capsicum species. In the latter, infection resulted in a severe reduction of growth, indicating the potential of this virus to be a significant crop pathogen. The name of chiltepin yellow mosaic virus (ChiYMV) is proposed for this new tymovirus

The Relationship of Within-Host Multiplication and Virulence in a Plant-Virus System

Background. Virulence does not represent any obvious advantage to parasites. Most models of virulence evolution assume that virulence is an unavoidable consequence of within-host multiplication of parasites, resulting in trade-offs between within-host multiplication and between-host transmission fitness components. Experimental support for the central assumption of this hypothesis, i.e., for a positive correlation between within-host multiplication rates and virulence, is limited for plant-parasite systems. Methodology/Principal Findings. We have addressed this issue in the system Arabidopsis thaliana-Cucumber mosaic virus (CMV). Virus multiplication and the effect of infection on plant growth and on viable seed production were quantified for 21 Arabidopsis wild genotypes infected by 3 CMV isolates. The effect of infection on plant growth and seed production depended of plant architecture and length of postembryonic life cycle, two genetically-determined traits, as well as on the time of infection in the plant's life cycle. A relationship between virus multiplication and virulence was not a general feature of this host-parasite system. This could be explained by tolerance mechanisms determined by the host genotype and operating differently on two components of plant fitness, biomass production and resource allocation to seeds. However, a positive relationship between virus multiplication and virulence was detected for some accessions with short life cycle and high seed weight to biomass ratio, which show lower levels of tolerance to infection. Conclusions/Significance. These results show that genotype-specific tolerance mechanisms may lead to the absence of a clear relationship between parasite multiplication and virulence. Furthermore, a positive correlation between parasite multiplication and virulence may occur only in some genotypes and/or environmental conditions for a given host-parasite system. Thus, our results challenge the general validity of the trade-off hypothesis for virulence evolution, and stress the need of considering the effect of both the host and parasite genotypes in analyses of host-parasite interactions. © 2007 Pagán et al.Ministerio de Educación y Ciencia, Spain.Peer Reviewe

The Relationship of Within-Host Multiplication and Virulence in a Plant-Virus System

Background. Virulence does not represent any obvious advantage to parasites. Most models of virulence evolution assume that virulence is an unavoidable consequence of within-host multiplication of parasites, resulting in trade-offs between within-host multiplication and between-host transmission fitness components. Experimental support for the central assumption of this hypothesis, i.e., for a positive correlation between within-host multiplication rates and virulence, is limited for plant-parasite systems. Methodology/Principal Findings. We have addressed this issue in the system Arabidopsis thaliana-Cucumber mosaic virus (CMV). Virus multiplication and the effect of infection on plant growth and on viable seed production were quantified for 21 Arabidopsis wild genotypes infected by 3 CMV isolates. The effect of infection on plant growth and seed production depended of plant architecture and length of postembryonic life cycle, two genetically-determined traits, as well as on the time of infection in the plant's life cycle. A relationship between virus multiplication and virulence was not a general feature of this host-parasite system. This could be explained by tolerance mechanisms determined by the host genotype and operating differently on two components of plant fitness, biomass production and resource allocation to seeds. However, a positive relationship between virus multiplication and virulence was detected for some accessions with short life cycle and high seed weight to biomass ratio, which show lower levels of tolerance to infection. Conclusions/Significance. These results show that genotype-specific tolerance mechanisms may lead to the absence of a clear relationship between parasite multiplication and virulence. Furthermore, a positive correlation between parasite multiplication and virulence may occur only in some genotypes and/or environmental conditions for a given host-parasite system. Thus, our results challenge the general validity of the trade-off hypothesis for virulence evolution, and stress the need of considering the effect of both the host and parasite genotypes in analyses of host-parasite interactions. © 2007 Pagán et al.Ministerio de Educación y Ciencia, Spain.Peer Reviewe

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Quasispecies Spatial Models for RNA Viruses with Different Replication Modes and Infection Strategies

Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along time