Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization of the sleep‐related neural systems in the brain of the harbour porpoise (Phocoena phocoena)

The present study provides the first systematic immunohistochemical neuroanatomical investigation of the systems involved in the control and regulation of sleep in an odontocete cetacean, the harbor porpoise (Phocoena phocoena). The odontocete cetaceans show an unusual form of mammalian sleep, with unihemispheric slow waves, suppressed REM sleep, and continuous bodily movement. All the neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals were present in the harbor porpoise, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity of nuclear organization relates to the cholinergic, noradrenergic, serotonergic, and orexinergic systems and is extended to the γ‐aminobutyric acid (GABA)ergic elements involved with these nuclei. Quantitative analysis of the cholinergic and noradrenergic nuclei of the pontine region revealed that in comparison with other mammals, the numbers of pontine cholinergic (126,776) and noradrenergic (122,878) neurons are markedly higher than in other large‐brained bihemispheric sleeping mammals. The diminutive telencephalic commissures (anterior commissure, corpus callosum, and hippocampal commissure) along with an enlarged posterior commissure and supernumerary pontine cholinergic and noradrenergic neurons indicate that the control of unihemispheric slow‐wave sleep is likely to be a function of interpontine competition, facilitated through the posterior commissure, in response to unilateral telencephalic input related to the drive for sleep. In addition, an expanded peripheral division of the dorsal raphe nuclear complex appears likely to play a role in the suppression of REM sleep in odontocete cetaceans. Thus, the current study provides several clues to the understanding of the neural control of the unusual sleep phenomenology present in odontocete cetaceans. J. Comp. Neurol. 524:1999–2017, 2016. © 2016 Wiley Periodicals, Inc.
Comparison of Different Antibody Clones for Immunohistochemistry Detection of Programmed Cell Death Ligand 1 (PD-L1) on Non–Small Cell Lung Carcinoma

Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues. Eight commercial available PD-L1 clones were tested and compared with a noncommercial PD-L1 antibody clone 5H1. Western blot and IHC using cell lines and human tissues were used to validate these clones. From all PD-L1 antibodies, only the clones E1L3N, E1J2J, SP142, 28-8, 22C3, and SP263 passed the Western blot and IHC validation, providing similar pattern than the clone 5H1 and then they were tested in 259 non–small cell lung cancer cases placed in 9 tissue microarrays. Among all cases, only those with ≥2 cores were included (185 cases). Positive and significant correlation was found between the median PD-L1 H-score in tumor and stroma compartments, for all selected antibodies. Overall, 56 of 185 cases were detected as positive cases in malignant cells expressing membranous PD-L1 by all the clones. However, the clone SP263 identified more PD-L1-positive cases compared with the other clones. Our results show that clones E1L3N, E1J2J, SP142, 28-8, 22C3, and SP263 provide positive membrane staining pattern comparable with clone 5H1. These commercial clones are comparable, but a careful evaluation by the pathologist is necessary to minimize error of positive misinterpretations.
Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial

Abstract Background. Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. Methods. We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6–35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). Results. Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6–17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64–2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82–2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59–2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79–2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. Conclusions. Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.
A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology

Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements. Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays. Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%). Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost.
Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

Introduction Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. Materials and Methods Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. Conclusion The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone.
How Spatial Heterogeneity of Cover Affects Patterns of Shrub Encroachment into Mesic Grasslands

We used a multi-method approach to analyze the spatial patterns of shrubs and cover types (plant species, litter or bare soil) in grassland-shrubland ecotones. This approach allows us to assess how fine-scale spatial heterogeneity of cover types affects the patterns of Cytisus balansae shrub encroachment into mesic mountain grasslands (Catalan Pyrenees, Spain). Spatial patterns and the spatial associations between juvenile shrubs and different cover types were assessed in mesic grasslands dominated by species with different palatabilities (palatable grass Festuca nigrescens and unpalatable grass Festuca eskia). A new index, called RISES (“Relative Index of Shrub Encroachment Susceptibility”), was proposed to calculate the chances of shrub encroachment into a given grassland, combining the magnitude of the spatial associations and the surface area for each cover type. Overall, juveniles showed positive associations with palatable F. nigrescens and negative associations with unpalatable F. eskia, although these associations shifted with shrub development stage. In F. eskia grasslands, bare soil showed a low scale of pattern and positive associations with juveniles. Although the highest RISES values were found in F. nigrescens plots, the number of juvenile Cytisus was similar in both types of grasslands. However, F. nigrescens grasslands showed the greatest number of juveniles in early development stage (i.e. height<10 cm) whereas F. eskia grasslands showed the greatest number of juveniles in late development stages (i.e. height>30 cm). We concluded that in F. eskia grasslands, where establishment may be constrained by the dominant cover type, the low scale of pattern on bare soil may result in higher chances of shrub establishment and survival. In contrast, although grasslands dominated by the palatable F. nigrescens may be more susceptible to shrub establishment; current grazing rates may reduce juvenile survival.
Efficiency of Some Organic Fertilizers as Safe Resources on the Performance of Valencia Orange Trees Grown in Newly Reclaimed Soils

This study was conducted during 2011and 2012 seasons on Valencia orange trees grown in newly reclaimed soil. Uniform trees at 12 years old budded on Volkamer lemon rootstock were selected and treated with three organic compost sorts i.e. Farmyard Manure (FM), Town Refuse (TR) and Sewage Sludge (SS) at 20 or 30% and/or natural extract of seaweed fungi (SW) at 25 or 50g/tree. Concerning the effect of compost sorts, results showed that sole application of farmyard manure followed in descending order by sewage sludge at 30% had improved leaf mineral contents, chlorophyll content, relative water content, fruit quality as well as total yield followed by Sewage Sludge. Using either farmyard or sewage sludge at 30%+25g seaweed extract revealed higher chemical constituents and yield values during both seasons. The best results were significantly obtained as seaweed extract at 50g/tree was combined with FM treatment followed by SS + 50g SW extract as compared with the other treatments. In addition, using composts at 20 or 30% in combinations with seaweed extract at 50g/tree gave higher values with non significant differences between them for every compost sort. The highest values were obtained as FM at 20 or 30% was used. Applying 20 or 30% compost + 50g seaweed recorded highest results with non differences between them. This means that using 50g seaweed extract + FM or SS compost sort at 20% /tree was sufficient for improving tree nutritional status, leaf chlorophyll content, fruit quality and total yield as well as useful in saving compost cost and reducing pollutions of chemical fertilizers.
Fault-tolerant operation of nine-level hybrid symmetric cascaded multilevel converter

Cascaded H-bridge multilevel converters are well-established solution for high power medium voltage industrial applications. However, the reliability of these converters is affected by the use of large number of power semiconductor devices. Fault-tolerant strategies improve reliability as well as availability of these converters by ensuring its operation even under device fault conditions. In this paper, the fault-tolerant operation of nine-level hybrid symmetric cascaded multilevel converter is explored for open- and short-circuit fault conditions. The converter operation is first analysed for the open-circuit fault condition. The converter reconfiguration and converter operations are then explained for short-circuit fault condition using neutral-shift and rebalancing fault tolerant strategies. The effectiveness of these techniques are then validated through simulation and experimental results.
Poor Hand Hygiene Procedure Compliance among Polish Medical Students and Physicians—The Result of an Ineffective Education Basis or the Impact of Organizational Culture?

Objective: The objective of the study was to examine the knowledge of Polish physicians and medical students about the role of hand hygiene (HH) in healthcare-associated infection (HAI) prevention. Study design: A survey was conducted using an author-prepared questionnaire, which was filled out on the first day of hospital work (or internship) by newly admitted physicians who had worked in other hospitals and students of different medical schools in Poland. Methods: 100 respondents participated in the study: 28 students, 18 medical interns and 54 physicians. Results: As many as 3/4 of physicians and students did not use the HH techniques correctly. The respondents declared that they perform HH in the following situations: 74.4% of respondents before an aseptic task; 60.8% before patient contact; 57.0% after patient contact; 11.5% after body fluid exposure risk, and only two respondents (1.1%) after contact with patient surroundings. 64% of respondents declared that their supervisor checked their knowledge of the HH technique when they were touching patients, but their supervisors checked the five instances for HH only in the case of 27 respondents (27%). Students experienced any control of HH in the workplace less often. Interns and physicians mentioned that the most important preventive action in HAI is HH, but for students it is the use of gloves. Conclusions: The level of knowledge and skills of physicians and students in the field of HH is insufficient. Deficiencies in skills and knowledge of HH were identified as early as at the level of the first internship.
Translation of HLA–HIV Associations to the Cellular Level: HIV Adapts To Inflate CD8 T Cell Responses against Nef and HLA-Adapted Variant Epitopes

Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA–HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA–HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design.
Genetic classifiers for remotely sensed images: Comparison with standard methods

In this article the effectiveness of some recently developed genetic algorithm-based pattern classifiers was investigated in the domain of satellite imagery which usually have complex and overlapping class boundaries. Landsat data, SPOT image and IRS image are considered as input. The superiority of these classifiers over k-NN rule, Bayes' maximum likelihood classifier and multilayer perceptron (MLP) for partitioning different landcover types is established. Results based on producer's accuracy (percentage recognition score), user's accuracy and kappa values are provided. Incorporation of the concept of variable length chromosomes and chromosome discrimination led to superior performance in terms of automatic evolution of the number of hyperplanes for modelling the class boundaries, and the convergence time. This non-parametric classifier requires very little a priori information, unlike k-NN rule and MLP (where the performance depends heavily on the value of k and the architecture, respectively), and Bayes' maximum likelihood classifier (where assumptions regarding the class distribution functions need to be made).
Genetic structure of Scomber japonicus (Perciformes: Scombridae) along the coast of China revealed by complete mitochondrial cytochrome b sequences

Abstract The phylogeography history and contemporary agents of selection for many marine fisheries, characterized by widespread species distributions in the face of significant harvest, remains poorly understood. Chub mackerel (Scomber japonicus) are a widespread species in the Indo-Pacific and represent one of the top five commercially fished species in the world, yet their phylogeographic history remains unknown. We characterized the genetic diversity, structure and demographic history of S. japonicus throughout adjacent Chinese seas (from the Yellow Sea to the South China Sea). Using 220 individuals from 11 sites, we inferred 55 distinct haplotypes from complete mitochondrial cytochrome b gene sequences. Haplotype diversity ranged from 0.505 to 0.967 and nucleotide diversity ranged from 0.00056 to 0.01042. Genetic differentiation (Fst) statistics suggested that the highest level of differentiation existed between the SanYa and SanSha localities (Fst = 0.86977), while the lowest levels of differentiation occurred between the DongGang and ShiDao localities (Fst ∼ 0). Kimura’s genetic distances ranged from 0.001 to 0.011 within and from 0.001 to 0.018 between populations. Hierarchical analysis of molecular variance, Neighbor-joining and median-joining network analyses identified significant phylogeographic structure with two localities (SanYa, Hainan of the South China Sea and LianYunGang, Jiangsu of the East China Sea) explaining most of the genetic variation observed, while the remaining populations were poorly differentiated.
Control of septin filament flexibility and bundling by subunit composition and nucleotide interactions

Septins self-assemble into heteromeric rods and filaments to act as scaffolds and modulate membrane properties. How cells tune the biophysical properties of septin filaments to control filament flexibility and length, and in turn the size, shape, and position of higher-order septin structures, is not well understood. We examined how rod composition and nucleotide availability influence physical properties of septins such as annealing, fragmentation, bundling, and bending. We found that septin complexes have symmetric termini, even when both Shs1 and Cdc11 are coexpressed. The relative proportion of Cdc11/Shs1 septin complexes controls the biophysical properties of filaments and influences the rate of annealing, fragmentation, and filament flexibility. Additionally, the presence and apparent exchange of guanine nucleotide also alters filament length and bundling. An Shs1 mutant that is predicted to alter nucleotide hydrolysis has altered filament length and dynamics in cells and impacts cell morphogenesis. These data show that modulating filament properties through rod composition and nucleotide binding can control formation of septin assemblies that have distinct physical properties and functions.