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Context.--Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS). Objective.--To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with [p16.sup.+] oropharyngeal squamous cell carcinoma (OPSCC). Design.--We identified 38 resected [p16.sup.+] OPSCCs for which paired PTs and LMs were available. PD-L1 immunohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement. Results.--Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens ([kappa] = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial ([kappa] = 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution ([kappa] = 0.84). Conclusions.--Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of [p16.sup.+] OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy. doi: 10.5858/arpa.2021-0464-OA, Over the last several years, immune checkpoint inhibitors targeting the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway have had a profound impact on the field of oncology. Immune checkpoint [...]

Hot on the heels of the November 2014 launch of the Nature Index, we are pleased to present a supplement dedicated to results from China, currently the country with the [...]

This first edition of the Nature Index 2014 Global supplement provides a snapshot of results from the new Nature Index. In this supplement, we turn a spotlight on the countries [...]

Highlights: [•] We observed several types of laughs in a natural speech corpus, and two predominant types of laughter (social vs. sincere) were categorized from a data manual examination of the data. [•] Global prosodic and laughter-specific acoustic features were extracted for the two types of laughter. These parameters were analysed by Principal Component Analysis and Classification Trees to reduce the number of parameters. [•] A Support Vector Machine was trained and tested using seven important features, and total classification accuracy was confirmed to be at least over 84 with unseen test material. [Copyright &y& Elsevier]

The principal polyunsaturated fatty acid acids found in brain, arachidonic acid (AA) and docosahexaenoic acid (DHA), preferentially accumulate in synaptic membranes. Although neurochemical studies have found that dietary-induced deficits in rat brain DHA composition significantly alter mesocorticolimbic dopamine (DA) neurotransmission, its impact on DA-mediated behavior remains poorly understood. In the present study, we determined the effects of dietary-induced deficits in brain DHA composition on amphetamine (AMPH)-induced locomotor activity and sensitization in DBA/2J mice, an inbred strain previously found to be hyporesponsive to AMPH, as well as monoamine concentrations in the PFC and ventral striatum following the AMPH challenge. Chronic dietary ω-3 fatty acid deficiency significantly decreased PFC (−25%) and ventral striatum (−20%) DHA composition, increased PFC (+7%) and ventral striatum (+6%) AA composition, and increased the AA:DHA ratio in PFC (+30%) and ventral striatum (+24%). The development and expression of AMPH-induced sensitization was significantly increased in DHA-deficient mice, whereas novelty- and acute AMPH-induced locomotor activity were not altered. DHA-deficient mice exhibited significantly greater ventral striatum, but not PFC, DA and DA metabolite concentrations following the AMPH challenge, whereas serotonin and noradrenalin concentrations were not altered. Ventral striatum AA composition and the AA:DHA ratio were both positively correlated with DA concentrations, and both ventral striatum AA composition and DA concentrations were positively correlated with locomotor activity during the preceding AMPH challenge. These results demonstrate that dietary-induced brain DHA deficiency, and associated elevation in the AA:DHA ratio, augment AMPH-induced sensitization in DBA/2J mice, and that this augmented response is associated with selective alterations in the mesolimbic DA pathway. Synapse 62:725-735, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This paper reports progress in the synthesis of conversational speech, from the viewpoint of work carried out on the analysis of a very large corpus of expressive speech in normal everyday situations. With recent developments in concatenative techniques, speech synthesis has overcome the barrier of realistically portraying extra-linguistic information by using the actual voice of a recognizable person as a source for units, combined with minimal use of signal processing. However, the technology still faces the problem of expressing paralinguistic information, i.e., the variety in the types of speech and laughter that a person might use in everyday social interactions. Paralinguistic modification of an utterance portrays the speaker's affective states and shows his or her relationships with the speaker through variations in the manner of speaking, by means of prosody and voice quality. These inflections are carried on the propositional content of an utterance, and can perhaps be modeled by rule, but they are also expresssed through nonverbal utterances, the complexity of which may be beyond the capabilities of many current synthesis methods. We suggest that this problem may be solved by the use of phrase-sized utterance units taken intact from a large corpus. [ABSTRACT FROM AUTHOR]

Idiosyncratic markers are features of genes and genomes that are so unusual that it is unlikely that they evolved more than once in a lineage of organisms. Here we explore further the potential of idiosyncratic markers and changes to typically conserved tRNA sequences for phylogenetic inference. Hard ticks were chosen as the model group because their phylogeny has been studied extensively. Fifty-eight candidate markers from hard ticks (family Ixodidae) and 22 markers from the subfamily Rhipicephalinae sensu lato were mapped onto phylogenies of these groups. Two of the most interesting markers, features of the secondary structure of two different tRNAs, gave strong support to the hypothesis that species of the Prostriata (Ixodes spp.) are monophyletic. Previous analyses of genes and morphology did not strongly support this relationship, instead suggesting that the Prostriata is paraphyletic with respect to the Metastriata (the rest of the hard ticks). Parallel or convergent evolution was not found in the arrangements of mitochondrial genes in ticks nor were there any reversals to the ancestral arthropod character state. Many of the markers identified were phylogenetically informative, whereas others should be informative with study of additional taxa. Idiosyncratic markers and changes to typically conserved nucleotides in tRNAs that are phylogenetically informative were common in this data set, and thus these types of markers might be found in other organisms. [ABSTRACT FROM AUTHOR]

The number of repeats in repetitive DNA like micro- and minisatellites is often determined by polymerase chain reaction (PCR). When we counted repeats in an array of mitochondrial repeats in the cattle tick ( Boophilus microplus) we found that the number of repeats increased during PCR. Multiplication of the repeats was independent of the primers used to amplify the region, the PCR annealing temperature and the length of the PCR product. The use of PCR to determine the number of repeats in arrays needs to be reassessed. For long repeats, a subset of samples should always be analysed by Southern blot hybridization to confirm the PCR results. [ABSTRACT FROM AUTHOR]

The complete arrangement of genes in the mitochondrial (mt) genome is known for 12 species of insects, and part of the gene arrangement in the mt genome is known for over 300 other species of insects. The arrangement of genes in the mt genome is very conserved in insects studied, since all of the protein-coding and rRNA genes and most of the tRNA genes are arranged in the same way. We sequenced the entire mt genome of the wallaby louse, Heterodoxus macropus, which is 14,670 bp long and has the 37 genes typical of animals and some noncoding regions. The largest noncoding region is 73 bp long (93% A+T), and the second largest is 47 bp long (92% A+T). Both of these noncoding regions seem to be able to form stem-loop structures. The arrangement of genes in the mt genome of this louse is unlike that of any other animal studied. All tRNA genes have moved and/or inverted relative to the ancestral gene arrangement of insects, which is present in the fruit fly Drosophila yakuba. At least nine protein-coding genes (atp6, atp8, cox2, cob, nad1–nad3, nad5, and nad6) have moved; moreover, four of these genes (atp6, atp8, nad1, and nad3) have inverted. The large number of gene rearrangements in the mt genome of H. macropus is unprecedented for an arthropod. [ABSTRACT FROM PUBLISHER]

The article discusses various reports published within the issue, including one on a method to transform neutral speech to expressive styles and another on the special needs of speech synthesis in conversational applications and the use of nonverbal utterances.

Discusses research being done on the pathway of double-strand break (DSB) rejoining dependent upon ataxia telangiectasia mutation, Artemis and proteins locating to ϒ-H2AX foci. Reference to a study by E. Riballo et al., published in the 2004 issue of "Molecular Cell"; Information on ataxia telangiectasia; Comparison between DSB formation and repair in ataxia telangiectasia mutation and artemis-defective cells.

Presents information on independent studies of Trypanosoma cruzi and Rafflesiaceae, which showed that there have been horizontal gene transfers between these parasites. Hypothesis made concerning the frequent integration of T. cruzi DNA into the host genome; Use of the rapid amplification of cDNA ends; Factor indicative of having kinetoplast minicircles integrations.

Investigates the influence of LINE-1 (L1) elements of DNA on transcription of endogenous genes. Abundance of L1 in mammalian genomes; Effect of open reading frames 2 sequence on gene expression; Comparison of the amount of L1 sequence in the genes with the highest and lowest levels of expression in humans.

Comments on the research paper "Major Events in the Genome Evolution of Vertebrates: Paranome Age and Size Differ Considerably Between Ray-Finned Fishes and Land Vertebrates," by Klaas Vandepoele, Wouter De Vos and their colleagues. Significance of the sequencing of the Fugu genome; Results of the analyses performed by the authors; Findings of the research.

Comments on the study "Extensive Gene Traffic on the Mammalian X Chromosome," by J. J. Emerson and colleagues. Findings of the authors' analysis of the human and mouse genomes; Effect of the inactivation of X-linked genes during meiosis; Possible reason for genes' move out of the X chromosome.

Reports on the discovery of a suite of genes from a coral. Number of expressed sequence tags (EST) that are lifted from a cDNA library of Acropora millepora; Percentage of the lifted EST clusters that matched with human genes; Implications of the discovery for genome research.

Deals with a study which analyzed the physiological role of Wnt/β-catenin signalling pathway in zebrafish. Analysis of the mechanisms of the tumor suppressor gene adenomatous polyposis coli (apc); Heart malformations associated with apc; Role of Wnt signalling in heart-valve precursors formation.

Discusses research being done on the comparative analyses of multi-species sequences From targeted genomic regions. Reference to a study by J. W. Thomas et al, published in the 2003 issue of the journal "Nature"; Characteristics of the genomic region; Similarities of the genes of the vertebrates; Analyses of multi-species conserved sequences; Differences genome sequences in mammals.

An introduction is presented in which the editor discusses various reports within the issue on topics including research, scientific literature and demographics.

Context.--Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS). Objective.--To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with p16þ oropharyngeal squamous cell carcinoma (OPSCC). Design.--We identified 38 resected p16+ OPSCCs for which paired PTs and LMs were available. PD-L1 immunohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement. Results.--Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens (Κ = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (Κ = 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution (Κ = 0.84). Conclusions.--Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of p16þ OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy. [ABSTRACT FROM AUTHOR]

Discusses two studies about the evolution of sex and how it maintains itself. Reference to a study by R. B. R. Azevedo and colleagues published in "Nature" and to a study by S. Paland and M. Lynch published in "Science"; Contrast between the sexual and asexual forms of the water flea Daphnia pulex; Modelling approach which tested whether negative epistasis evolves as a result of sexual reproduction.

The article focuses on a new study which indicates that inhibiting mutation in the genomes of pathogenic bacteria might be a viable strategy for dealing with the growing problem of antibiotic resistance. The researchers have used resistance to ciprofloxacin in Escherichia coli as their model system. Ciprofloxacin interferes with the action of topoisomerases, so mutations in topoisomerase-encoding genes confer ciprofloxacin resistance in bacteria.

Discusses research being done on the link of variation in a gene that underlies a winged versus wingless polymorphism in male aphids to plasticity of the same trait in females. Reference to a study by Christian Braendle and colleagues in the March 30, 2005 issue of "Proceedings of the Royal Society of London Series B"; Importance of phenotypic plasticity; Analysis of parthenogenetic female clones of the pea aphid, Acrythosiphon pisum; Inverse relationship of the female polyphenism and the male polymorphism.

Discusses research being done on a computational and experimental approach to validating gene predictions in the Drosophila melanogaster genome. Reference to a study by Mark Yandell, Adina Bailey, Sima Misra et al, published in a 2002 issue of the "Proceedings of the National Academy of Sciences USA"; Analysis of the gene transcripts of the genome.

Discusses research being done on the clustering of Hox genes throughout the genome of the tunicate Oikopleura dioica. Reference to study by H.-C. Seo and colleagues, published in the 2004 issue of the journal "Nature"; Significance of Hox genes for specifying differential development in bilaterally symmetrical animals; Analysis of full-length complementary DNA in the species.

Deals with the creation of a standard molecular timetable of gene-expression profiles to address the lack of clinically applicable methods of body time detection. Advantage that the timetable will allegedly bring to drug administration; Role played by a best-fitted cosine curve in the effort taken; Way to detect circadian rhythmicity.

Features LegislativeDatabase, a web-based searchable database for U.S. genetics-related policy and legislative documents, from the National Human Genome Research Institute. Purpose of creating the database; Contents; Value-added feature that the database incorporates.

Assesses the capability of DNA microarray technology in the detection of stable gene-expression differences in individuals. Variation in the expression of peripheral blood leukocytes; Identification of individual-specific genes; Representation of interferon-inducible genes in the pattern of individual-specific genes.

Examines the expression patterns of key developmental genes in anemone. Assessment of body axes in bilateral cnidarians; Patterns of expression during N. vectensis development; Similarities of Hox-like genes in expression patterns.

Reports on a proposal of Sir John Sulston, Nobel-prize winning leader of the Human Genome Project, to introduce laws that will prevent genetic discrimination. Effort of professor Sulston and his co-authors Professors John Harris ad Simona Giordana from Manchester University in Great Britain, to circulate their proposal to the Human Genetics Commission; Focus of the effort on providing equal treatment for people regardless of their genetic make-up; Concern of Sulston on a possible misuse of information acquired from genetic tests.

Discusses a research on developmental biology, which focused on genes that controls hair and bristle development. Role of large frizzled (Fz) family of genes, first identified in Drosophila melanogaster, on hair patterning among mammals; Characterization of mammalian Fz genes; Identification of the role of Fz6 in mammalian tissue polarity.