Predicting the next round of drugs for Medicare price negotiation.

There is uncertainty regarding which brand-name prescription drugs will have their prices negotiated by Medicare in 2025. This Viewpoint analyzes the process that will be used to select the next 15 drugs for price negotiation.

Improved inference of population histories by integrating genomic and epigenomic data.

With the availability of high-quality full genome polymorphism (SNPs) data, it becomes feasible to study the past demographic and selective history of populations in exquisite detail. However, such inferences still suffer from a lack of statistical resolution for recent, for example bottlenecks, events, and/or for populations with small nucleotide diversity. Additional heritable (epi)genetic markers, such as indels, transposable elements, microsatellites, or cytosine methylation, may provide further, yet untapped, information on the recent past population history.

Inference of Host-Pathogen Interaction Matrices from Genome-Wide Polymorphism Data.

Host-pathogen coevolution is defined as the reciprocal evolutionary changes in both species due to genotype × genotype (G×G) interactions at the genetic level determining the outcome and severity of infection. While co-analyses of hosts and pathogen genomes (co-genome-wide association studies) allow us to pinpoint the interacting genes, these do not reveal which host genotype(s) is/are resistant to which pathogen genotype(s). The knowledge of this so-called infection matrix is important for agriculture and medicine.

Neutral genetic structuring of pathogen populations during rapid adaptation.

Pathogen species are experiencing strong joint demographic and selective events, especially when they adapt to a new host, for example through overcoming plant resistance. Stochasticity in the founding event and the associated demographic variations hinder our understanding of the expected evolutionary trajectories and the genetic structure emerging at both neutral and selected loci. What would be the typical genetic signatures of such a rapid adaptation event is not elucidated.

Weak seed banks influence the signature and detectability of selective sweeps.

Seed banking (or dormancy) is a widespread bet-hedging strategy, generating a form of population overlap, which decreases the magnitude of genetic drift. The methodological complexity of integrating this trait implies it is ignored when developing tools to detect selective sweeps. But, as dormancy lengthens the ancestral recombination graph (ARG), increasing times to fixation, it can change the genomic signatures of selection.

Determinants of rapid adaptation in species with large variance in offspring production.

The speed of population adaptation to changing biotic and abiotic environments is determined by the interaction between genetic drift, positive selection and linkage effects. Many marine species (fish, crustaceans), invertebrates and pathogens of humans and crops, exhibit sweepstakes reproduction characterized by the production of a very large amount of offspring (fecundity phase) from which only a small fraction may survive to the next generation (viability phase). Using stochastic simulations, we investigate whether the occurrence of sweepstakes reproduction affects the efficiency of a positively selected unlinked locus, and thus, the speed of adaptation since fecundity and/or viability have distinguishable consequences on mutation rate, probability and fixation time of advantageous alleles.

Joint inference of evolutionary transitions to self-fertilization and demographic history using whole-genome sequences.

The evolution from outcrossing to selfing occurred recently across the eukaryote tree of life in plants, animals, fungi, and algae. Despite short-term advantages, selfing is hypothetically an evolutionary dead-end reproductive strategy. The tippy distribution on phylogenies suggests that most selfing species are of recent origin.

Approximate Bayesian Computation applied to time series of population genetic data disentangles rapid genetic changes and demographic variations in a pathogen population.

Adaptation can occur at remarkably short timescales in natural populations, leading to drastic changes in phenotypes and genotype frequencies over a few generations only. The inference of demographic parameters can allow understanding how evolutionary forces interact and shape the genetic trajectories of populations during rapid adaptation. Here we propose a new Approximate Bayesian Computation (ABC) framework that couples a forward and individual-based model with temporal genetic data to disentangle genetic changes and demographic variations in a case of rapid adaptation.

Genome-wide characterization of the gene family in tomato () and their relatedness to disease resistance.

Nucleotide-binding leucine-rich-repeat receptors (NLR), the largest group of genes associated with plant disease resistance (R), have attracted attention due to their crucial role in protecting plants from pathogens. Genome-wide studies of NLRs have revealed conserved domains in the annotated tomato genome. The 321 genes identified in the tomato genome have been randomly mapped to 12 chromosomes.

Selective sweeps linked to the colonization of novel habitats and climatic changes in a wild tomato species.

Positive selection is the driving force underpinning local adaptation and leaves footprints of selective sweeps on the underlying major genes. Quantifying the timing of selection and revealing the genetic bases of adaptation in plant species occurring in steep and varying environmental gradients are crucial to predict a species' ability to colonize new niches. We use whole-genome sequence data from six populations across three different habitats of the wild tomato species Solanum chilense to infer the past demographic history and search for genes under strong positive selection.

Echo chambers and opinion dynamics explain the occurrence of vaccination hesitancy.

Vaccination hesitancy is a major obstacle to achieving and maintaining herd immunity. Therefore, public health authorities need to understand the dynamics of an anti-vaccine opinion in the population. We introduce a spatially structured mathematical model of opinion dynamics with reinforcement.

Circularly polarized luminescence from Tb(III) interacting with chiral polyether macrocycles.

A straightforward two-step synthesis protocol affords a series of chiral amide-based bis-pyridine substituted polyether macrocycles. One ligand is particularly able to complex terbium(III) ions spontaneously. Upon complexation, interesting chiroptical properties are observed both in absorbance (ECD) and in fluorescence (CPL).

Life-History traits and the replicator equation.

Due to the relevance for conservation biology, there is an increasing interest to extend evolutionary genomics models to plant, animal or microbial species. However, this requires to understand the effect of life-history traits absent in humans on genomic evolution. In this context, it is fundamentally of interest to generalize the replicator equation, which is at the heart of most population genomics models.

Approximate Bayesian Computation Untangles Signatures of Contemporary and Historical Hybridization between Two Endangered Species.

Contemporary gene flow, when resumed after a period of isolation, can have crucial consequences for endangered species, as it can both increase the supply of adaptive alleles and erode local adaptation. Determining the history of gene flow and thus the importance of contemporary hybridization, however, is notoriously difficult. Here, we focus on two endangered plant species, Arabis nemorensis and A.

Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort.

Purpose: To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution.

Methods And Materials: NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures.

High silver concentrations in biological samples following different exposures: Two case reports.

Background: Silver is used in various industrial applications, but also in confectioneries and for therapeutic use due to its antibiotic properties. Its toxicity is not well documented and most often only in the context of professional exposure.

Aim: Here we report two cases of high silver concentrations in biological samples in two women: the first patient presented grey marks around her cuticles, probably due to her consumption of silvered sweets and the second patient presented agranulocytosis and thrombocytopenia occurring within 24 h after the topical application of a cream containing sulfadiazine and silver to burns over a large surface area.

Limits and convergence properties of the sequentially Markovian coalescent.

Several methods based on the sequentially Markovian coalescent (SMC) make use of full genome sequence data from samples to infer population demographic history including past changes in population size, admixture, migration events and population structure. More recently, the original theoretical framework has been extended to allow the simultaneous estimation of population size changes along with other life history traits such as selfing or seed banking. The latter developments enhance the applicability of SMC methods to nonmodel species.

Correction: Inference of past demography, dormancy and self-fertilization rates from whole genome sequence data.

[This corrects the article DOI: 10.1371/journal.pgen.

High-Grade Gliomas Located in the Right Hemisphere Are Associated With Worse Quality of Life.

Background: The impact of glioma location on quality of life (QOL) has not been conclusively studied, possibly due to the prohibitively high sample size that standard statistical analyses would require and the inherent heterogeneity of this disease. By using a novel algorithm, we investigated the impact of tumor location on QOL in a limited set of 53 consecutive patients.

Methods: The glial tumors of 53 consecutive patients were segmented and registered to a standardized atlas.

Synthesis, Characterization, and Reactivity of a Hypervalent-Iodine-Based Nitrooxylating Reagent.

Herein, the synthesis and characterization of a hypervalent-iodine-based reagent that enables a direct and selective nitrooxylation of enolizable C-H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy-to-handle, and delivers the nitrooxy (-ONO ) group under mild reaction conditions. Activation of the reagent by Brønsted and Lewis acids was demonstrated in the synthesis of nitrooxylated β-keto esters, 1,3-diketones, and malonates, while its activity under photoredox catalysis was shown in the synthesis of nitrooxylated oxindoles.