Miracle-dz/UniFAR-FTUs huggingface dataset:
IL2/Anti-IL2 Complex Combined with CTLA-4, But Not PD-1, Blockade Rescues Antitumor NK Cell Function by Regulatory T-cell Modulation

Combination of IL2/anti-IL2 complexes (IL2Cx) with PD-1 or CTLA-4 pathway blockade controls tumor growth and acts differentially on CD8+, NK cells, and Treg cells. Only the IL2Cx/anti–CTLA-4 combination is dependent upon NK cells. High-dose IL2 immunotherapy can induce long-lasting cancer regression but is toxic and insufficiently efficacious. Improvements are obtained with IL2/anti-IL2 complexes (IL2Cx), which redirect IL2 action to CD8+ T and natural killer (NK) cells. Here, we evaluated the efficacy of combining IL2Cx with blockade of inhibitory immune pathways. In an autochthonous lung adenocarcinoma model, we show that the IL2Cx/anti–PD-1 combination increases CD8+ T-cell infiltration of the lung and controls tumor growth. In the B16-OVA model, which is resistant to checkpoint inhibition, combination of IL2Cx with PD-1 or CTLA-4 pathway blockade reverses that resistance. Both combinations work by reinvigorating exhausted intratumoral CD8+ T cells and by increasing the breadth of tumor-specific T-cell responses. However, only the IL2Cx/anti–CTLA-4 combination is able to rescue NK cell antitumor function by modulating intratumoral regulatory T cells. Overall, association of IL2Cx with PD-1 or CTLA-4 pathway blockade acts by different cellular mechanisms, paving the way for the rational design of combinatorial antitumor therapies.
Terpenes and lignans from the roots of Solanum melongena L.

Abstract Phytochemical investigation of the roots of Solanum melongena L. resulted in the isolation of ten terpenes and sixteen lignans, including a new triterpene saponin, officinoterpenoside E (1) and twenty-five known compounds (2-26). All compounds were firstly isolated from S. melongena except 2, 13, 21, 22. The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with high-resolution mass spectrometric analysis. All compounds were evaluated for the cytotoxicity against three cancer cell lines (HepG2, Hela, and MCF-7) in vitro. The results showed that compounds 1, 6, 20, 25 and 26 exhibited moderate cytotoxicity against HepG2, Hela and MCF-7 cells with IC50 values in the range of 16.8 ± 1.7 to 29.1 ± 1.9 μM. Therefore, these terpenoids and lignans may have potential biological activity, and also seemed to be of great chemotaxonomic value for S. melongena. Graphical Abstract
Saccadic Eye Movements Smear Spatial Working Memory

Why do saccades interfere with spatial working memory? One possibility is that attention and saccades are tightly coupled, and performing a saccade momentarily removes attention from spatial working memory, degrading the memory representation. This cannot be the entire explanation, because saccades cause greater interference than do covert attentional shifts (Lawrence, Myerson, & Abrams, 2004). In addition, this saccadic degradation is limited to spatial but not object, configural, or verbal representations. We propose that saccadic remapping is partially responsible for this increased interference. To test this, we used a spatial change detection task, and during the retention interval, participants either performed a central task, a peripheral task without an eye movement, or a peripheral task that required a saccade. Using the method of constant stimuli allowed us to fit psychophysical functions in which we derived measures of spatial memory precision, guessing, and response bias. It is important that we found a directionally specific loss of memory precision, such that memory representations were less precise along the axis of the saccade. This was beyond the general loss of precision we found for covert shifts, suggesting that part of the effect is because of remapping. Saccades also increased guessing, but unlike the loss of precision, the effect was nondirectional.
Polymerizable Ionic Liquids for Solid-State Polymer Electrolytes

Eight new polymerizable ammonium-TFSI ionic liquids were synthesized and characterized with respect to an application in energy storage devices. The ionic liquids feature methacrylate or acrylate termination as polymerizable groups. The preparation was optimized to obtain the precursors and ionic liquids in high yield. All products were characterized by NMR and IR spectroscopy. Phase transition temperatures were obtained by DSC analysis. Density, viscosity and ionic conductivity of the ionic liquids were compared and discussed. The results reveal that the length of attached alkyl groups as well as the methyl group at the polymerizable function have significant influences on the ionic liquids physicochemical properties. Ionic conductivity values vary between 0.264 mS cm−1 for [C2NA,22]TFSI and 0.080 mS cm−1 for [C8NMA,22]TFSI at 25 °C. Viscosity values are within a range of 0.762 Pa s for [C2NA,22]TFSI and 1.522 Pa s for [C6NMA,22]TFSI at 25 °C.
Highly Resolved Phylogenetic Relationships within Order Acipenseriformes According to Novel Nuclear Markers

Order Acipenseriformes contains 27 extant species distributed across the northern hemisphere, including so-called “living fossil” species of garfish and sturgeons. Previous studies have focused on their mitochondrial genetics and have rarely used nuclear genetic data, leaving questions as to their phylogenetic relationships. This study aimed to utilize a bioinformatics approach to screen for candidate single-copy nuclear genes, using transcriptomic data from sturgeon species and genomic data from the spotted gar, Lepisosteus oculatus. We utilized nested polymerase chain reaction (PCR) and degenerate primers to identify nuclear protein-coding (NPC) gene markers to determine phylogenetic relationships among the Acipenseriformes. We identified 193 nuclear single-copy genes, selected from 1850 candidate genes with at least one exon larger than 700 bp. Forty-three of these genes were used for primer design and development of 30 NPC markers, which were sequenced for at least 14 Acipenseriformes species. Twenty-seven NPC markers were found completely in 16 species. Gene trees according to Bayesian inference (BI) and maximum likelihood (ML) were calculated based on the 30 NPC markers (20,946 bp total). Both gene and species trees produced very similar topologies. A molecular clock model estimated the divergence time between sturgeon and paddlefish at 204.1 Mya, approximately 10% later than previous estimates based on cytochrome b data (184.4 Mya). The successful development and application of NPC markers provides a new perspective and insight for the phylogenetic relationships of Acipenseriformes. Furthermore, the newly developed nuclear markers may be useful in further studies on the conservation, evolution, and genomic biology of this group.
The Prostate Cancer Rehabilitation Clinic: a biopsychosocial clinic for sexual dysfunction after radical prostatectomy.

Purpose The most prevalent intervention for localized prostate cancer (pca) is radical prostatectomy (rp), which has a 10-year relative survival rate of more than 90%. The improved survival rate has led to a focus on reducing the burden of treatment-related morbidity and improving the patient and partner survivorship experience. Post-rp sexual dysfunction (sdf) has received significant attention, given its substantial effect on patient and partner health-related quality of life. Accordingly, there is a need for sdf treatment to be a fundamental component of pca survivorship programming. Methods Most research about the treatment of post-rp sdf involves biomedical interventions for erectile dysfunction (ed). Although findings support the effectiveness of pro-erectile agents and devices, most patients discontinue use of such aids within 1 year after their rp. Because side effects of pro-erectile treatment have proved to be inadequate in explaining the gap between efficacy and ongoing use, current research focuses on a biopsychosocial perspective of ed. Unfortunately, there is a dearth of literature describing the components of a biopsychosocial program designed for the post-rp population and their partners. Results In this paper, we detail the development of the Prostate Cancer Rehabilitation Clinic (pcrc), which emphasizes multidisciplinary intervention teams, active participation by the partner, and a broad-spectrum medical, psychological, and interpersonal approach. Conclusions The goal of the pcrc is to help patients and their partners achieve optimal sexual health and couple intimacy after rp, and to help design cost-effective and beneficial rehabilitation programs.
Preference for emotionally meaningful activity in Alzheimer’s disease

Abstract Objectives: Socioemotional selectivity theory (SST) contends that future time perspective is the central determinant of healthy older adults’ prioritization of emotional gratification. We have shown elsewhere that individuals with Alzheimer’s disease (AD) are disoriented to future time perspective. This study examined whether these same participants would prioritize emotional gratification despite having distorted time perspective. Method: Performance of individuals with Alzheimer’s disease (AD) was compared against young, young-old, and old-old adults on a social activity preference card-sort task. We examined whether activity preferences differentially related to subjective wellbeing. Results: Multidimensional scaling revealed common dimensions along which groups considered social activities. The importance of these dimensions varied across healthy participant groups in ways predicted by SST. Dimensions related to knowledge acquisition were more important in youth than older age; emotional dimensions were more important to the older age groups. Despite AD, these individuals also prioritzed emotional gratification, suggesting that cognitive impairment is not a barrier to socioemotional selectivity. Preference for emotionally meaningful activities was positively associated with subjective wellbeing. Conclusion: Persons with AD are motivated towards emotionally meaningful ends and retain high levels of wellbeing. These findings have implications in the caregiving context for shaping social programs to better match goals and preferences.
Transient Knock-Down of Prefrontal DISC1 in Immune-Challenged Mice Causes Abnormal Long-Range Coupling and Cognitive Dysfunction throughout Development

Compromised brain development has been hypothesized to account for mental illness. This concept was underpinned by the function of the molecule disrupted-in-schizophrenia 1 (DISC1), which represents an intracellular hub of developmental processes and has been related to cognitive dysfunction in psychiatric disorders. Mice with whole-brain DISC1 knock-down show impaired prefrontal–hippocampal function and cognitive abilities throughout development and at adulthood, especially when combined with early environmental stressors, such as maternal immune activation (MIA). However, the contribution of abnormal DISC1-driven maturation of either prefrontal cortex (PFC) or hippocampus (HP) to these deficits is still unknown. Here, we use in utero electroporation to restrict the DISC1 knock-down to prefrontal layer II/III pyramidal neurons during perinatal development and expose these mice to MIA as an environmental stressor (dual-hit GPFCE mice, both sexes). Combining in vivo electrophysiology and neuroanatomy with behavioral testing, we show that GPFCE mice at neonatal age have abnormal patterns of oscillatory activity and firing in PFC, but not HP. Abnormal firing rates in PFC of GPFCE mice relate to sparser dendritic arborization and lower spine density. Moreover, the long-range coupling within prefrontal–hippocampal networks is decreased at this age. The transient prefrontal DISC1 knock-down was sufficient to permanently perturb the prefrontal–hippocampal communication and caused poorer recognition memory performance at pre-juvenile age. Thus, developmental dysfunction of prefrontal circuitry causes long-lasting disturbances related to mental illness. SIGNIFICANCE STATEMENT Hypofrontality is considered a main cause of cognitive deficits in mental disorders, yet the underlying mechanisms are still largely unknown. During development, long before the emergence of disease symptoms, the functional coupling within the prefrontal–hippocampal network, which is the core brain circuit involved in cognitive processing, is reduced. To assess to which extent impaired prefrontal development contributes to the early dysfunction, immune-challenged mice with transient DISC1 knock-down confined to PFC were investigated in their prefrontal–hippocampal communication throughout development by in vivo electrophysiology and behavioral testing. We show that perturbing developmental processes of prefrontal layer II/III pyramidal neurons is sufficient to diminish prefrontal–hippocampal coupling and decrease the cognitive performance throughout development.
The Big Five Inventory–2: Replication of Psychometric Properties in a Dutch Adaptation and First Evidence for the Discriminant Predictive Validity of the Facet Scales

Abstract This series of studies investigated whether the good psychometric properties of the English version of the Big Five Inventory–2 (BFI–2) could be replicated using its Dutch adaptation. Second, it aimed to further examine the predictive validity of both the Big Five domain and the more specific facet scales of the BFI–2 in a large and representative sample. Results indicated that the structure found in the English version was replicated in the Dutch adaptation. The 60-item BFI–2 was reliable at the level of both domains and facets, as were the abbreviated versions. In terms of validity, the domain scales predicted a broad range of criteria. Examination of preregistered hypotheses regarding the discriminant validity of the facets indicated that experts were able to predict which facets would be most strongly associated with specific criteria. Overall, results confirm the strong psychometric properties of the BFI–2 Big Five domain scales and indicate that theoretically identified facets can be more valid predictors of criteria than other facets of the same domain.
Reduced willingness to approach genuine smilers in social anxiety explained by potential for social evaluation, not misperception of smile authenticity

ABSTRACT We investigate perception of, and responses to, facial expression authenticity for the first time in social anxiety, testing genuine and polite smiles. Experiment 1 (N = 141) found perception of smile authenticity was unaffected, but that approach ratings, which are known to be reduced in social anxiety for happy faces, are more strongly reduced for genuine than polite smiles. Moreover, we found an independent contribution of social anxiety to approach ratings, over and above general negative affect (state/trait anxiety, depression), only for genuine smiles, and not for polite ones. We argue this pattern of results can be explained by genuine smilers signalling greater potential for interaction – and thus greater potential for the scrutiny that is feared in social anxiety – than polite smiles. Experiment 2 established that, relative to polite smilers, genuine smilers are indeed perceived as friendlier and likely to want to talk for longer if approached. Critically, the degree to which individual face items were perceived as wanting to interact correlated strongly with the amount that social anxiety reduced willingness to approach in Experiment 1. We conclude it is the potential for social evaluation and scrutiny signalled by happy expressions, rather than their positive valence, that is important in social anxiety.
Living on the edge: biofilms developing in oscillating environmental conditions

Abstract For the first time, the densities and diversity of microorganisms developed on ocean gliders were investigated using flow cytometry and Illumina MiSeq sequencing of 16S and 18S rRNA genes. Ocean gliders are autonomous buoyancy-driven underwater vehicles, equipped with sensors continuously recording physical, chemical, and biological parameters. Microbial biofilms were investigated on unprotected parts of the glider and surfaces coated with base, biocidal and chitosan paints. Biofilms on the glider were exposed to periodical oscillations of salinity, oxygen, temperature, pressure, depth and light, due to periodic ascending and descending of the vehicle. Among the unprotected surfaces, the highest microbial abundance was observed on the bottom of the glider’s body, while the lowest density was recorded on the glider’s nose. Antifouling paints had the lowest densities of microorganisms. Multidimensional analysis showed that the microbial communities formed on unprotected parts of the glider were significantly different from those on biocidal paint and in seawater.
Health and related indicators : indicators

This chapter presents a selection of the best available data on the functioning and performance of the South African health system. It also questions whether the data provide evidence of a system that is truly based on Primary Health Care principles. Accordingly, it draws attention to data on the social determinants of health, which received particular attention at Alma Ata and have been highlighted once again with the release of the World Health Organization's World Health Report this year. The available evidence reflects enormous variability in the quality of information in the different health information systems as well as variability in the risk factors and determinants of health, health care delivery, as well as health outcomes. Overall the information available suggests that while progress has been made with policy formulation and some inputs (e.g. financing) and processes (e.g. immunisation), inadequate provision and maldistribution of human resources linked with incomplete implementation of policies has resulted in ongoing inequities. Some outcome and impact indicators, measured in terms of morbidity and mortality, show either little improvement or even deterioration over time. The implementation of both health care delivery and information systems do not accommodate the interdepartmental and interdisciplinary responses that are required to adequately address the social determinants of poor health and achieve comprehensive Primary Health Care. This challenge has to be faced in relation not only to infectious diseases, but also in relation to the increasing burden of chronic non-communicable diseases. The sections for which data are included are given in the table of contents following.
Picture quality measures in image compression systems

A major problem in evaluating picture quality in image compression systems is the extreme difficulty in describing the type and amount of degradation in reconstructed image. Because of the inherent drawbacks associated with the subjective measures of picture quality, there has been a great deal of interest in developing an objective measure that can be used as a substitute. The aim of this paper is to examine a set of objective picture quality measures for application in still image compression systems and to highlight the correlation of these measures with subjective picture quality measures. Picture quality is measured using nine different objective picture quality measures and subjectively using mean opinion score (MOS) as a measure of perceived picture quality. The correlation between each objective measure and MOS is found. The effects of different image compression ratios are assessed and the best objective measures are proposed. Our results show that some objective measures correlate well with the perceived picture quality for a given compression algorithm but they are not reliable for an evaluation across different algorithms. So, we compared objective picture quality measures across different algorithms and we found measures, which serve well in all tested image compression systems.
Predicting EGFR mutation status in lung adenocarcinoma on computed tomography image using deep learning

Epidermal growth factor receptor (EGFR) genotyping is critical for treatment guidelines such as the use of tyrosine kinase inhibitors in lung adenocarcinoma. Conventional identification of EGFR genotype requires biopsy and sequence testing which is invasive and may suffer from the difficulty of accessing tissue samples. Here, we propose a deep learning model to predict EGFR mutation status in lung adenocarcinoma using non-invasive computed tomography (CT). We retrospectively collected data from 844 lung adenocarcinoma patients with pre-operative CT images, EGFR mutation and clinical information from two hospitals. An end-to-end deep learning model was proposed to predict the EGFR mutation status by CT scanning. By training in 14 926 CT images, the deep learning model achieved encouraging predictive performance in both the primary cohort (n=603; AUC 0.85, 95% CI 0.83–0.88) and the independent validation cohort (n=241; AUC 0.81, 95% CI 0.79–0.83), which showed significant improvement over previous studies using hand-crafted CT features or clinical characteristics (p<0.001). The deep learning score demonstrated significant differences in EGFR-mutant and EGFR-wild type tumours (p<0.001). Since CT is routinely used in lung cancer diagnosis, the deep learning model provides a non-invasive and easy-to-use method for EGFR mutation status prediction. Deep learning provides a noninvasive method for EGFR mutation prediction (AUC 0.81) in lung adenocarcinoma, which shows significant improvement over using hand-crafted CT features or clinical characteristics http://ow.ly/LtDJ30nhc5Q
Endothelial Cell–Targeted Deletion of PPARγ Blocks Rosiglitazone-Induced Plasma Volume Expansion and Vascular Remodeling in Adipose Tissue

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor γ (PPARγ) agonists that represent an effective class of insulin-sensitizing agents; however, clinical use is associated with weight gain and peripheral edema. To elucidate the role of PPARγ expression in endothelial cells (ECs) in these side effects, EC-targeted PPARγ knockout (PpargΔEC) mice were placed on a high-fat diet to promote PPARγ agonist–induced plasma volume expansion, and then treated with the TZD rosiglitazone. Compared with Pparg-floxed wild-type control (Ppargf/f) mice, PpargΔEC treated with rosiglitazone are resistant to an increase in extracellular fluid, water content in epididymal and inguinal white adipose tissue, and plasma volume expansion. Interestingly, histologic assessment confirmed significant rosiglitazone-mediated capillary dilation within white adipose tissue of Ppargf/f mice, but not PpargΔEC mice. Analysis of ECs isolated from untreated mice in both strains suggested the involvement of changes in endothelial junction formation. Specifically, compared with cells from Ppargf/f mice, PpargΔEC cells had a 15-fold increase in focal adhesion kinase, critically important in EC focal adhesions, and >3-fold significant increase in vascular endothelial cadherin, the main component of focal adhesions. Together, these results indicate that rosiglitazone has direct effects on the endothelium via PPARγ activation and point toward a critical role for PPARγ in ECs during rosiglitazone-mediated plasma volume expansion.