Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxytocin Receptors Are Expressed by Glutamatergic Prefrontal Cortical Neurons That Selectively Modulate Social Recognition

Social recognition, the ability to recognize individuals that were previously encountered, requires complex integration of sensory inputs with previous experience. Here, we use a variety of approaches to discern how oxytocin-sensitive neurons in the PFC exert descending control over a circuit mediating social recognition in mice. Using male mice with Cre-recombinase directed to the oxytocin receptor gene (Oxtr), we revealed that oxytocin receptors (OXTRs) are expressed on glutamatergic neurons in the PFC, optogenetic stimulation of which elicited activation of neurons residing in several mesolimbic brain structures. Optogenetic stimulation of axons in the BLA arising from OXTR-expressing neurons in the PFC eliminated the ability to distinguish novel from familiar conspecifics, but remarkably, distinguishing between novel and familiar objects was unaffected. These results suggest that an oxytocin-sensitive PFC to BLA circuit is required for social recognition. The implication is that impaired social memory may manifest from dysregulation of this circuit. SIGNIFICANCE STATEMENT Using mice, we demonstrate that optogenetic activation of the neurons in the PFC that express the oxytocin receptor gene (Oxtr) impairs the ability to distinguish between novel and familiar conspecifics, but the ability to distinguish between novel and familiar objects remains intact. Subjects with autism spectrum disorders (ASDs) have difficulty identifying a person based on remembering facial features; however, ASDs and typical subjects perform similarly when remembering objects. In subjects with ASD, viewing the same face increases neural activity in the PFC, which may be analogous to the optogenetic excitation of oxytocin receptor (OXTR) expressing neurons in the PFC that impairs social recognition in mice. The implication is that overactivation of OXTR-expressing neurons in the PFC may contribute to ASD symptomology.
Does Orbital Volume Change Using the Mirror Technique Have a Correlation With Posttraumatic Enophthalmos?

An increase in orbital volume (OV) is an important factor in posttraumatic enophthalmos. The aim of this study was to evaluate the correlation of OV change using the mirror technique with posttraumatic enophthalmos.In this cross-sectional study, a 3-dimensional (3D) semi-automated volumetric method, using a 3D volume rendering tool, was applied to measure OV. The total orbital volume difference (TOVD), posterior orbital volume difference (POVD), and anterior orbital volume difference (AOVD) were measured as predictive factors in traumatic and intact orbits. Enophthalmos was also examined as the outcome, using a Hertel exophthalmometer.A total of 27 patients were examined in this study. The mean TOVD was 4.48 ± 1.82 mm, the mean POVD was 1.91 ± 0.31 mm, and the mean AOVD was 2.57 ± 1.71 mm; also, the mean enophthalmos was 2.89 ± 1.12 mm. Pearson's correlation test demonstrated a positive correlation between enophthalmos and TOVD, POVD, and AOVD (P <0.05). Based on the linear regression model, TOVD had a predictive power of 61.7% for enophthalmos. For every 1-mm volume change, a 0.38-mm enophthalmos was expected (R, 0.617; B, 0.38; P = 0.001). TOVD, POVD, and AOVD showed strong correlations with enophthalmos. However, it seems that POVD has the greatest effects on the occurrence of posttraumatic enophthalmos.
Factors Affecting Tamoxifen Metabolism in Patients With Breast Cancer: Preliminary Results of the French PHACS Study

In addition to the effect of cytochrome P450 (CYP) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)‐pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast cancer included in a prospective multicenter study. Plasma concentrations of tamoxifen and six major metabolites, the genotype for 63 single‐nucleotide polymorphisms, and comedications were obtained 6 months after treatment initiation. Plasma concentrations of endoxifen were significantly associated with CYP2D6 diplotype (P < 0.0001), CYP3A4*22 genotype (P = 0.0003), and concomitant intake of potent CYP2D6 inhibitors (P < 0.001). Comparison of endoxifen levels showed that the CYP2D6 phenotype classification could be improved by grouping intermediate metabolizer (IM)/IM and IM/poor metabolizer diplotype into IM phenotype for future use in tamoxifen therapy optimization. Finally, the multivariable regression analysis showed that formation of tamoxifen metabolites was independently impacted by CYP2D6 diplotype and CYP3A4*22, CYP2C19*2, and CYP2B6*6 genetic polymorphisms.
The Strength of Alpha–Beta Oscillatory Coupling Predicts Motor Timing Precision

Precise timing makes the difference between harmony and cacophony, but how the brain achieves precision during timing is unknown. In this study, human participants (7 females, 5 males) generated a time interval while being recorded with magnetoencephalography. Building on the proposal that the coupling of neural oscillations provides a temporal code for information processing in the brain, we tested whether the strength of oscillatory coupling was sensitive to self-generated temporal precision. On a per individual basis, we show the presence of alpha–beta phase–amplitude coupling whose strength was associated with the temporal precision of self-generated time intervals, not with their absolute duration. Our results provide evidence that active oscillatory coupling engages α oscillations in maintaining the precision of an endogenous temporal motor goal encoded in β power; the when of self-timed actions. We propose that oscillatory coupling indexes the variance of neuronal computations, which translates into the precision of an individual's behavioral performance. SIGNIFICANCE STATEMENT Which neural mechanisms enable precise volitional timing in the brain is unknown, yet accurate and precise timing is essential in every realm of life. In this study, we build on the hypothesis that neural oscillations, and their coupling across time scales, are essential for the coding and for the transmission of information in the brain. We show the presence of alpha–beta phase–amplitude coupling (α–β PAC) whose strength was associated with the temporal precision of self-generated time intervals, not with their absolute duration. α–β PAC indexes the temporal precision with which information is represented in an individual's brain. Our results link large-scale neuronal variability on the one hand, and individuals' timing precision, on the other.
Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13

The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the United States in 2010. Using a large paediatric carriage sample collected from shortly after the introduction of PCV-7 to several years after the introduction of PCV-13, we investigate alterations in the composition of the pneumococcal population following the introduction of PCV-13, evaluating the extent to which the post-vaccination non-vaccine type (NVT) population mirrors that from prior to vaccine introduction and the effect of PCV-13 on vaccine type lineages. Draft genome assemblies from 736 newly sequenced and 616 previously published pneumococcal carriage isolates from children in Massachusetts between 2001 and 2014 were analysed. Isolates were classified into one of 22 sequence clusters (SCs) on the basis of their core genome sequence. We calculated the SC diversity for each sampling period as the probability that any two randomly drawn isolates from that period belong to different SCs. The sampling period immediately after the introduction of PCV-13 (2011) was found to have higher diversity than preceding (2007) or subsequent (2014) sampling periods {Simpson’s D 2007: 0.915 [95 % confidence interval (CI) 0.901, 0.929]; 2011: 0.935 [0.927, 0.942]; 2014 : 0.912 [0.901, 0.923]}. Amongst NVT isolates, we found the distribution of SCs in 2011 to be significantly different from that in 2007 or 2014 (Fisher’s exact test P=0.018, 0.0078), but did not find a difference comparing 2007 to 2014 (Fisher’s exact test P=0.24), indicating greater similarity between samples separated by a longer time period than between samples from closer time periods. We also found changes in the accessory gene content of the NVT population between 2007 and 2011 to have been reduced by 2014. Amongst the new serotypes targeted by PCV-13, four were present in our sample. The proportion of our sample composed of PCV-13-only vaccine serotypes 19A, 6C and 7F decreased between 2007 and 2014, but no such reduction was seen for serotype 3. We did, however, observe differences in the genetic composition of the pre- and post-PCV-13 serotype 3 population. Our isolates were collected during discrete sampling periods from a small geographical area, which may limit the generalizability of our findings. Pneumococcal diversity increased immediately following the introduction of PCV-13, but subsequently returned to pre-vaccination levels. This is reflected in the distribution of NVT lineages, and, to a lesser extent, their accessory gene frequencies. As such, there may be a period during which the population is particularly disrupted by vaccination before returning to a more stable distribution. The persistence and shifting genetic composition of serotype 3 is a concern and warrants further investigation.
Age‐dependent DNA methylation patterns on the Y chromosome in elderly males

The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging‐related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood‐based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome‐wide epigenetic association analysis to detect Y‐linked CpGs differentially methylated over age and cross‐validated the significant CpGs in the four cohorts. We identified 40–219 significant CpG sites (false discovery rate <0.05) with >82% of them hypermethylated with increasing age, which is in strong contrast to the patterns reported on the autosomal chromosomes. Comparing the rate of change in the Y‐linked DNA methylation across cohorts that represent different age intervals revealed a trend of acceleration in DNA methylation with increasing age. The age‐dependent DNA methylation patterns on the Y chromosome were further examined for their association with all‐cause mortality with results suggesting that the predominant pattern of age‐related hypermethylation on the Y chromosome is associated with reduced risk of death.
Antifungal, Antibacterial, and Antioxidant Activities of Acacia Saligna (Labill.) H. L. Wendl. Flower Extract: HPLC Analysis of Phenolic and Flavonoid Compounds

In this study, for the environmental development, the antifungal, antibacterial, and antioxidant activities of a water extract of flowers from Acacia saligna (Labill.) H. L. Wendl. were evaluated. The extract concentrations were prepared by dissolving them in 10% DMSO. Wood samples of Melia azedarach were treated with water extract, and the antifungal activity was examined at concentrations of 0%, 1%, 2%, and 3% against three mold fungi; Fusarium culmorum MH352452, Rhizoctonia solani MH352450, and Penicillium chrysogenum MH352451 that cause root rot, cankers, and green fruit rot, respectively, isolated from infected Citrus sinensis L. Antibacterial evaluation of the extract was assayed against four phytopathogenic bacteria, including Agrobacterium tumefaciens, Enterobacter cloacae, Erwinia amylovora, and Pectobacterium carotovorum subsp. carotovorum, using the micro-dilution method to determine the minimum inhibitory concentrations (MICs). Further, the antioxidant capacity of the water extract was measured via 2,2′-diphenylpicrylhydrazyl (DPPH). Phenolic and flavonoid compounds in the water extract were analyzed using HPLC: benzoic acid, caffeine, and o-coumaric acid were the most abundant phenolic compounds; while the flavonoid compounds naringenin, quercetin, and kaempferol were identified compared with the standard flavonoid compounds. The antioxidant activity of the water extract in terms of IC50 was considered weak (463.71 μg/mL) compared to the standard used, butylated hydroxytoluene (BHT) (6.26 μg/mL). The MIC values were 200, 300, 300, and 100 µg/mL against the growth of A. tumefaciens, E. cloacae, E. amylovora, and P. carotovorum subsp. carotovorum, respectively, which were lower than the positive control used (Tobramycin 10 μg/disc). By increasing the extract concentration, the percentage inhibition of fungal mycelial was significantly increased compared to the control treatment, especially against P. chrysogenum, suggesting that the use of A. saligna flower extract as an environmentally friendly wood bio-preservative inhibited the growth of molds that cause discoloration of wood and wood products.
Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain

ABSTRACT In the adult rodent brain, neural stem cells (NSCs) persist in the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ), which are specialized niches in which young neurons for the olfactory bulb (OB) and hippocampus, respectively, are generated. Recent studies have significantly modified earlier views on the mechanisms of NSC self-renewal and neurogenesis in the adult brain. Here, we discuss the molecular control, heterogeneity, regional specification and cell division modes of V-SVZ NSCs, and draw comparisons with NSCs in the SGZ. We highlight how V-SVZ NSCs are regulated by local signals from their immediate neighbors, as well as by neurotransmitters and factors that are secreted by distant neurons, the choroid plexus and vasculature. We also review recent advances in single cell RNA analyses that reveal the complexity of adult neurogenesis. These findings set the stage for a better understanding of adult neurogenesis, a process that one day may inspire new approaches to brain repair. Summary: This Review discusses the identification, regulation and heterogeneity of neural stem cells and examines recent insights into their transcriptomic properties and mechanism of persistence into adulthood.
Improving the management of musculoskeletal conditions: can an alternative approach to referral management underpinned by quality improvement and behavioural change theories offer a solution and a better patient experience? A mixed-methods study

Objectives To assess whether a quality improvement-based approach to referral management can result in better musculoskeletal care within general practice. Design Prospective cohort study using mixed methodology including random-effects meta-analysis and interrupted time series. Setting and participants 36 general practices in East London. Intervention Informed by the results of a Cochrane review on educational interventions to improve general practitioners’ (GPs) musculoskeletal care, we developed a multifaceted intervention, underpinned by quality improvement and behavioural change theories. It combined locally agreed clinical pathways, feedback on referral rates, clinical audit and peer review. Main outcome measures Referral letter content, pathway adherence, referral rates, inter-practice variability and patient experience were evaluated before and after the intervention. Results Referral letter content on suspected diagnosis and prior management improved from a pooled preintervention proportion of 59% (95% CI 53% to 65%) and 67% (95% CI 61% to 73%), respectively, to 77% (95% CI 70% to 84%) and 81% (95% CI 74% to 88%). Pathway adherence improved from a pooled preintervention percentage of 42% (95% CI 35% to 48%) to 66% (95% CI 57% to 76%). The effect was greater across all quality outcomes for practices with baseline performance below or equal to the pooled baseline performance. There were reductions in the variability and rates of orthopaedic referrals at 6, 12 and 18 months (referral rate relative effect 32% (95% CI 14% to 48%), 30% (95% CI 7% to 53%) and 30% (95% CI 0% to 59%), respectively). Patient rating of how well GPs explained the musculoskeletal condition improved by 29% (95% CI 14% to 43%) and patient perception on the usefulness of the GP appointment improved by 24% (95% CI 9% to 38%). Conclusions A quality improvement-based approach to referral management which values GPs’ professionalism can result in improvements across a range of outcomes including referral quality, patient experience, referral rates and variability.
Towards a systematic understanding of structure–function relationship of dimethylsulfoniopropionate‐catabolizing enzymes

Each year, several million tons of dimethylsulfoniopropionate (DMSP) are produced by marine phytoplankton and bacteria as an important osmolyte to regulate their cellular osmosis. Microbial breakdown of DMSP to the volatile gas dimethylsulfide (DMS) plays an important role in global biogeochemical cycles of the sulphur element between land and the sea. Understanding the enzymes involved in the transformation of DMSP and DMS holds the key to a better understanding of oceanic DMSP cycles. Recent work by Shao et al. (2019) has resolved the crystal structure of two important enzymes, DmdB and DmdC, involved in DMSP transformation through the demethylation pathway. Their work represents an important step towards a systematic understanding of the structure–function relationships of DMSP‐catabolizing enzymes in marine microbes.
Nutritional properties of organic and conventional beef meat at retail.

BACKGROUND Consumers perceive that organic meat has superior nutritional properties compared to conventional meat, although the available evidence from commercial samples is very scarce. The present study compared the nutritional composition of organic and conventional beef meat sold at retail, including, for the first time, the bioactive compounds coenzyme Q10 , carnosine, anserine, creatine and taurine. Sampling comprised two muscles: longissimus thoracis and supraspinatus. RESULTS Organic beef had 17% less cholesterol, 32% less fat, 16% less fatty acids, 24% less monounsaturated fatty acids, 170% more α-linolenic acid, 24% more α-tocopherol, 53% more β-carotene, 34% more coenzyme Q10 and 72% more taurine than conventional beef. Differences between organic and conventional samples were clearly dependent on the muscle because longissimus thoracis and supraspinatus showed different patterns of compound accumulation. CONCLUSION To our knowledge, a higher amount of bioactive compounds in organic beef meat is reported for the first time in the present study. Retail organic beef had a higher nutritional value than retail conventional beef, which resulted from better-balanced lipid and bioactive compound contents. © 2019 Society of Chemical Industry.
Direct and bystander effects in human blood lymphocytes exposed to 241Am alpha particles and the relative biological effectiveness using chromosomal aberration and micronucleus assay

Abstract Purpose: It is important to understand the significance of alpha (α) radiation-induced bystander effects (RIBE) and its relative biological effectiveness (RBE); this is because the phenomenon is not universal and the mechanism is unclear and because the RBE is widely varying and projected to be very high. Materials and methods: Isolated lymphocytes from healthy volunteers (n = 10) were exposed to either low fluence α-particles (241Am), γ-rays (60Co), or X-rays (225 kVp and 6 MV). Co-culture methodology was employed to investigate bystander effects (BEs). Chromosomal aberrations (CA) and micronucleus (MN) formation were used to study the BE and calculated RBE. Results: Lymphocytes directly exposed to the types of radiation used showed a dose-dependent increase in the frequency of CA and MN; dose independent increases in the frequency of these chromosomal damages in co-cultured bystander cells, implies that all three types of radiation-induced a BE. The calculated RBE at the level of 5% induced aberrations varied between 9 and 20. Conclusion: The magnitude of low fluence α-particle induced RIBE is higher than in low LET (linear energy transfer) radiation. The RBE also varies depending upon the endpoints used and adds up to targeted effects. Since the endpoint of CA is considered as an important and early marker of risk prediction, the RIBE and RBE using CA as a marker are relevant for radiation protection purposes.
Histone Modification Marks Strongly Regulate CDH1 Promoter in Prostospheres as A Model of Prostate Cancer Stem Like Cells

Objective Cadherin-1 (CDH1) plays an important role in the metastasis, while expression of this protein is under control of epigenetic changes on its gene promoter. Therefore we evaluated both DNA methylation (DNAmet) and histone modification marks of CDH1 in prostate cancer stem like cells (PCSLCs). Materials and Methods In this experimental study, we isolated PCSLCs using cell surface marker and prostaspheroid formation, respectively. The cells isolated from both methods were characterized and then the levels of H3K4me2, H3K27me3, H3K9me2/3 and H3K9ac as well as DNAmet were assessed in CDH1 promoter of the isolated cells. Results The CD44+ CD49hi cells were not validated as PCSLCs. However, prostaspheres overexpressed stemness related genes and had higher ability of invasion potential, associated with reduction in CDH1 expression. Epigenetic status analysis showed that CDH1 promoter was hypo-methylated. Histone modifications of H3K9ac and H3K4me3 were significantly reduced, in parallel with an increased level of H3K27me3. Conclusion Our results suggest that slight decrease of DNAmet of the CpG island in CDH1 promoter does not significantly contribute to the change of CDH1 expression. Therefore, histone modifications are responsible in repressing CDH1 in PCSLCs.
Treatment of fractures of the distal radius and ulna in toy breed dogs with circular external skeletal fixation: a retrospective study

Summary Objective: To evaluate the effectiveness of circular external skeletal fixation (CESF) in treating fractures of the distal radius and ulna in toy breed dogs, and to document the type and frequency of complications associated with this technique. Methods: The medical records of small breed dogs with fractures of the distal radius and ulna admitted to the University of Turin and to the Clinica Ferretti between 2002 and 2009 were retrospectively reviewed. The criteria for inclusion of cases in the study were: body weight of 5 kg or less, transverse or short oblique fracture of the distal third of the radius and ulna, no previous repair attempts, and treatment with CESF as the sole method of fixation. Results: Twenty fractures in 16 dogs satisfied the criteria for inclusion into this study. No signs of infection or failure of fixation were detected in any case. Mean frontal plane alignment was 4.7° ± 2.7° and mean sagittal plane alignment was 12.7° ± 7.2°. Postoperative complications occurred in one patient. All fractures achieved union. Mean time until radiographic evidence of a bridging callus and subsequent implant removal was 71 days (range: 30–120). Conclusions: The results of this study support the use of CESF for treatment of fractures of the distal radius and ulna in toy breed dogs as an alternative to other methods of fracture fixation. However, this technique requires a series of follow-up examinations to evaluate the stability of the apparatus, the soundness of the wires and to determine the appropriate time for implant removal.