Miracle-dz/UniFAR-FTUs huggingface dataset:
Solid Lipid Nanoparticles for Dibucaine Sustained Release

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72–89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.
Glucose variability during delirium in diabetic and non-diabetic intensive care unit patients: A prospective cohort study

Purpose To determine whether glucose variability is altered during delirium days compared to non-delirious days in critically ill patients with and without diabetes in the intensive care unit (ICU). Materials and methods Critically ill patients with delirious and non-delirious days during ICU stay were included from a prospective cohort study which was conducted from January 2011- June 2013. Glucose variability was measured each observation day using various definitions (change in mean glucose, standard deviation, mean absolute glucose, daily delta and occurrence of hypo- and hyperglycemia). Mixed-effects models and generalized mixed-effects models with logit link function were performed to study the association between delirium and glucose variability, adjusting for potential confounders. Results With the exception of the risk of hypoglycemia, delirium was not linked to higher glucose variability using the various definitions of this estimate. For hypoglycemia, we did find an association with delirium in diabetic patients (OR adj.: 2.78; 95% CI: 1.71–6.32, p = 0.005), but not in non-diabetic patients (OR adj.: 1.16; 95% CI: 0.58–2.28, p = 0.689). Conclusions Despite the positive association between delirium and hypoglycemia in critically ill patients with diabetes, delirium was not associated with more pronounced glucose variability. Our findings suggest that glucose levels should be monitored more closely in diabetic patients during delirium at the ICU to prevent hypoglycemia.
Unraveling the Role of Vegetables in Spreading Antimicrobial-Resistant Bacteria: A Need for Quantitative Risk Assessment

Abstract In recent years, vegetables gain consumer attraction due to their reputation of being healthy in combination with low energy density. However, since fresh produce is often eaten raw, it may also be a source for foodborne illness. The presence of antibiotic-resistant bacteria might pose a particular risk to the consumer. Therefore, this review aims to present the current state of knowledge concerning the exposure of humans to antibiotic-resistant bacteria via food of plant origin for quantitative risk assessment purposes. The review provides a critical overview of available information on hazard identification and characterization, exposure assessment, and risk prevention with special respect to potential sources of contamination and infection chains. Several comprehensive studies are accessible regarding major antimicrobial-resistant foodborne pathogens (e.g., Salmonella spp., Listeria spp., Bacillus cereus, Campylobacter spp., Escherichia coli) and other bacteria (e.g., further Enterobacteriaceae, Pseudomonas spp., Gram-positive cocci). These studies revealed vegetables to be a potential—although rare—vector for extended-spectrum beta-lactamase-producing Enterobacteriaceae, mcr1-positive E. coli, colistin- and carbapenem-resistant Pseudomonas aeruginosa, linezolid-resistant enterococci and staphylococci, and vancomycin-resistant enterococci. Even if this provides first clues for assessing the risk related to vegetable-borne antimicrobial-resistant bacteria, the literature research reveals important knowledge gaps affecting almost every part of risk assessment and management. Especially, the need for (comparable) quantitative data as well as data on possible contamination sources other than irrigation water, organic fertilizer, and soil becomes obvious. Most crucially, dose–response studies would be needed to convert a theoretical “risk” (e.g., related to antimicrobial-resistant commensals and opportunistic pathogens) into a quantitative risk estimate.
Work-disability in low back pain patients with or without surgery, and the role of social insurance regulation changes in Sweden.

BACKGROUND The aims were to study the differences in work-disability in patients with low back pain (LBP) in relation to (i) treatment provided (non-surgical or lumber spine surgery (decompression or fusion), and (ii) two time points, i.e. before and after the social insurance regulation changes in the in 2008. METHODS All non-pensioned individuals, aged 19-60 years, living in Sweden, diagnosed with LBP in 2004-06 or 2008-10 were included (n = 153739). Hazard ratios (HRs) with 95% confidence intervals for long-term sickness absence (>90 days, LTSA) and disability pension (DP) for LBP-patients (non-surgical, decompression, fusion, both surgeries) were estimated by Cox regression compared with the matched references from the general population without LBP (n = 566008). RESULTS LBP-patients had a higher risk of subsequent work-disability compared with the references before and after insurance regulation changes. LBP-patients receiving decompression surgery had similar risk for later work-disability as those treated non-surgically. However, following regulation changes, LBP-patients undergoing fusion surgery had higher risk estimates of both LTSA (HR: 3.3) and DP (HR: 4.8) than patients treated non-surgically (HR: LTSA 2.1; DP 2.5) or with decompression (HR: LTSA 2.6; DP 2.1). In the adjusted models, risk estimates mainly attenuated after controlling for previous sickness absence. CONCLUSION Risk for subsequent work-disability among LBP-patients was higher compared with people without LBP and lumbar spine surgery. Discrepancies in risk were explained by the treatment provided previous sickness absence and changes in the social insurance regulations, specifically LBP-patients treated with fusion surgery had an increased risk of subsequent work-disability after changes in regulations.
A problem in the structure assignment of acremolin C, which is most probably identical with acremolin B

Abstract With the help of chemical shifts computed with density functional theory (DFT), it is demonstrated that the reported experimental 13C NMR data of acremolin C are incompatible with the claimed structure of an N2,3-ethenoguanine with an isopropyl group at C-1'. An alternative structure, which is in agreement with both experimental and computed data, presents an isopropyl group at the C-2' position of an N2,3-ethenoguanine and leads to the conclusion that acremolin C is identical with acremolin B. Graphical Abstract
Membrane insertion and intercellular transfer of glycosylphosphatidylinositol-anchored proteins: potential therapeutic applications

Abstract Anchorage of a subset of cell surface proteins in eukaryotic cells is mediated by a glycosylphosphatidylinositol (GPI) moiety covalently attached to the carboxy-terminus of the protein moiety. Experimental evidence for the potential of GPI-anchored proteins (GPI-AP) of being released from cells into the extracellular environment has been accumulating, which involves either the loss or retention of the GPI anchor. Release of GPI-AP from donor cells may occur spontaneously or in response to endogenous or environmental signals. The experimental evidence for direct insertion of exogenous GPI-AP equipped with the complete anchor structure into the outer plasma membrane bilayer leaflets of acceptor cells is reviewed as well as the potential underlying molecular mechanisms. Furthermore, promiscuous transfer of certain GPI-AP between plasma membranes of different cells in vivo under certain (patho)physiological conditions has been reported. Engineering of target cell surfaces using chimeric GPI-AP with complete GPI anchor may be useful for therapeutic applications.
Rapid and Efficient Production of Human Functional Mast Cells through a Three-Dimensional Culture of Adipose Tissue–Derived Stromal Vascular Cells

Mast cells (MC) are innate immune cells involved in many physiological and pathological processes. However, studies of MC function and biology are hampered by the difficulties to obtain human primary MC. To solve this problem, we established a new method to produce easily and rapidly high numbers of MC for in vitro studies using human adipose tissue, which is an abundant and easy access tissue. Stromal vascular fraction of adipose tissue, obtained from human abdominal dermolipectomy, was cultured as spheroids in serum free medium supplemented in stem cell factor. Using this method, we generated, within 3 wk, a highly pure population of connective tissue–type MC expressing MC typical peptidases (tryptase, chymase, and carboxypeptidase-A3) with a yield increasing over time. Stem cell factor was required for this culture, but unlike MC derived from CD34+ cells, this culture did not depend on IL-3 and -6. MC obtained with this method degranulated following FcεRI cross-linking or stimulation by C5a, compound 48/80, and substance P. Interestingly, activation by anti-IgE of both white adipose tissue–MC and MC obtained from peripheral blood–derived CD34+ pluripotent progenitor cells induced the production of PGs as well as proinflammatory cytokines (TNF-α, Il-6, and GM-CSF). In conclusion, we developed a new time saving and reproducible method to produce highly pure and functional human MC in 3 wk from human adipose tissue.
Strengthening Teachers in Disadvantaged Schools: Evidence from an Intervention in Sweden's Poorest City Districts

ABSTRACT Children growing up in disadvantaged neighborhoods perform much worse in school compared to children growing up under more favorable circumstances. We examine a program (“Coaching for Teaching”) targeted at ten lower secondary schools in Sweden's most disadvantaged city districts. The program's aim was to enhance student performance by strengthening the teachers’ professional development. Using a difference-in-differences design we estimate effects on several outcomes. We find a positive and statistically significant impact on student performance on standardized tests in English. Estimates for several other outcomes are also positive, but not statistically significant. For test scores in Swedish there is no improvement. An analysis of a survey among pupils supports the idea that the intervention enhanced the teaching and the classroom climate.
Hyperglycemia Affects miRNAs Expression Pattern during Adipogenesis of Human Visceral Adipocytes—Is Memorization Involved?

microRNAs are increasingly analyzed in adipogenesis, whose deregulation, especially visceral, contributes to the development of diabetes. Hyperglycemia is known to affect cells while occurring acutely and chronically. Therefore, we aimed to evaluate the effect of hyperglycemia on human visceral pre/adipocytes from the perspective of microRNAs. The relative expression of 78 microRNAs was determined by TaqMan Low Density Arrays at three stages of HPA-v adipogenesis conducted under normoglycemia, chronic, and intermittent hyperglycemia (30 mM). Hierarchical clustering/Pearson correlation revealed the relationship between various microRNAs’ expression profiles, while functional analysis identified the genes and signaling pathways regulated by differentially expressed microRNAs. Hyperglycemia affected microRNAs’ expression patterns during adipogenesis, and at the stage of pre-adipocytes, differentiated and mature adipocytes compared to normoglycemia. Interestingly, the changes that were evoked upon hyperglycemic exposure during one adipogenesis stage resembled those observed upon chronic hyperglycemia. At least 15 microRNAs were modulated during normoglycemic and/or hyperglycemic adipogenesis and/or upon intermittent/chronic hyperglycemia. Bioinformatics analysis revealed the involvement of these microRNAs in cell cycle, lipid metabolism, ECM–receptor interaction, oxidative stress, signaling of insulin, MAPK, TGF-β, p53, and more. The obtained data suggests that visceral pre/adipocytes exposed to chronic/intermittent hyperglycemia develop a microRNAs’ expression pattern, which may contribute to further visceral dysfunction, the progression of diabetic phenotype, and diabetic complications possibly involving “epi”-memory.
Interspecific variation of olfactory preferences in flies, mice, and humans

Aiming to unravel interspecific differences in olfactory preferences, we performed comparative studies of odor valence in flies, mice, and humans. Our analysis revealed that odor preferences of flies correlate positively with the ones of mice and negatively with the ones of humans, but found no evidence supporting the hypothesis that humans and mice prefer the same odors. We further find that odorants eliciting the highest and lowest preferences are often advertising critical biological sources (e.g., food or oviposition sites), suggesting that evolutionary pressures reflecting the ecological needs of each species shape olfactory preferences.
Design of a 3D BMP-2-Delivering Tannylated PCL Scaffold and Its Anti-Oxidant, Anti-Inflammatory, and Osteogenic Effects In Vitro

In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.
(Gravitational) Vacuum Cherenkov Radiation

This work reviews our current understanding of Cherenkov-type processes in vacuum that may occur due to a possible violation of Lorentz invariance. The description of Lorentz violation is based on the Standard Model Extension (SME). To get an overview as general as possible, the most important findings for vacuum Cherenkov radiation in Minkowski spacetime are discussed. After doing so, special emphasis is put on gravitational Cherenkov radiation. For a better understanding, the essential properties of the gravitational SME are recalled in this context. The common grounds and differences of vacuum Cherenkov radiation in Minkowski spacetime and in the gravity sector are emphasized.
Resistance protein Pit interacts with the GEF OsSPK1 to activate OsRac1 and trigger rice immunity

Significance The plant genome encodes resistance (R) genes that are one of the major genomic resources to enhance disease resistance in various crops. R gene products, R proteins, serve as intracellular receptors for pathogen effectors, leading to activation of effector-triggered immunity. Due to the importance of R proteins, elucidation of their signaling pathways is an important research goal. We revealed that OsSPK1, a GDP/GTP exchange factor for the small GTPase OsRac1, is a direct binding protein of the rice R protein Pit, which is a resistance protein to rice blast fungus. OsSPK1 is a key signaling molecule in Pit signaling. Our results provide a critical new insight into molecular mechanisms underlying R protein activation and new knowledge for crop improvement. Resistance (R) genes encode intracellular nucleotide-binding/leucine-rich repeat-containing (NLR) family proteins that serve as critical plant immune receptors to induce effector-triggered immunity (ETI). NLR proteins possess a tripartite domain architecture consisting of an N-terminal variable region, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat. N-terminal coiled-coil (CC) or Toll-interleukin 1 receptor (TIR) domains of R proteins appear to serve as platforms to trigger immune responses, because overexpression of the CC or TIR domain of some R proteins is sufficient to induce an immune response. Because direct downstream signaling molecules of R proteins remain obscure, the molecular mechanisms by which R proteins regulate downstream signaling are largely unknown. We reported previously that a rice R protein named Pit triggers ETI through a small GTPase, OsRac1, although how Pit activates OsRac1 is unclear. Here, we identified OsSPK1, a DOCK family guanine nucleotide exchange factor, as an interactor of Pit and activator for OsRac1. OsSPK1 contributes to signaling by two disease-resistance genes, Pit and Pia, against the rice blast fungus Magnaporthe oryzae and facilitates OsRac1 activation in vitro and in vivo. The CC domain of Pit is required for its binding to OsSPK1, OsRac1 activation, and the induction of cell death. Overall, we conclude that OsSPK1 is a direct and key signaling target of Pit-mediated immunity. Our results shed light on how R proteins trigger ETI through direct downstream molecules.
Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA–miRNA–mRNA Regulatory Network

Background A variety of treatment strategies have been developed for clear cell kidney carcinoma (KIRC); however, there is still a need for effective therapeutic targets and prognostic molecular biomarkers. Given that long noncoding RNAs (lncRNAs) has been emerging as an important regulator in tumorigenesis, we explored potential functional lncRNAs in KIRC by comprehensively analyzing the lncRNA–miRNA–mRNA regulatory network with bioinformatics processing tools. Material/Methods RNA-seq/miRNA-seq data of KIRC in The Cancer Genome Atlas (TCGA) were obtained and analyzed. The “edgeR” package in R software was used to identify differentially expressed lncRNAs (DElncRNAs, differentially expressed long noncoding RNAs), miRNAs (DEmiRNAs, differentially expressed micro RNAs), and mRNAs (DEmRNAs, differentially expressed messenger RNAs) in KIRC and normal samples. A global triple network was conducted based on the competing endogenous RNA (ceRNA) theory, and survival analysis was conducted by “survival” package in R software. Results A total of 4246 DElncRNAs, 179 DEmiRNAs, and 5758 DEmRNAs were identified, among which a subset of them (321 lncRNAs, 26 miRNAs, and 1068 mRNAs) were found to constitute a global ceRNA network in KIRC. Four lncRNAs (ENTPD3-AS1, FGD5-AS1, LIFR-AS1, and UBAC2-AS1) were revealed to be potential therapeutic targets as well as prognostic biomarkers of KIRC by our extensive functional analysis. Conclusions We reported here the identification of functional lncRNAs in KIRC via a TCGA data-based bioinformatics analysis. We believe that this study might contribute to improving the comprehension of the lncRNA-mediated ceRNA regulatory mechanisms in the tumorigenesis of KIRC. Meanwhile, our results suggested that 4 lncRNAs might act as potential therapeutic targets or candidate prognostic biomarkers in KIRC.
Neural evidence for persistent attentional bias to threats in patients with social anxiety disorder

Abstract Does the biased attention toward social threats dwells on or disappears in patients with social anxiety disorder (SAD)? We investigated the neural mechanism of attentional bias in terms of attentional capture and holding in SAD. A total of 31 SAD patients and 30 healthy controls performed a continuous performance task detecting the orientation of a red letter ‘T’ while angry or neutral face distractors appeared or disappeared at the center of the screen. Behaviorally, typical attentional capture effects were found in response to abruptly appearing distractors in both groups. The patient group showed significant attentional dwelling effects in response to the angry face distractor only. Patients showed increased neural activity in the amygdala, insula/inferior frontal gyrus (IFG) and temporo-parietal junction (TPJ) compared with those of controls for the abruptly appearing angry distractor. Patients also maintained increased activities in brain regions related to attentional reorienting to distractor, namely the TPJ and IFG in line with their behavioral results of attentional holding effects. Our results indicate that patients with SAD showed prolonged attentional bias to task-irrelevant social threats. The underlying mechanism of prolonged attentional bias in SAD was indicated with amygdala hyperactivity and continued activity of the bottom-up attention network including the TPJ and IFG.
Preliminary Evidence of a Missing Self Bias in Face Perception for Individuals with Dissociative Identity Disorder

ABSTRACT Failing to recognize one’s mirror image can signal an abnormality in one’s sense of self. In dissociative identity disorder (DID), individuals often report that their mirror image can feel unfamiliar or distorted. They also experience some of their own thoughts, emotions, and bodily sensations as if they are nonautobiographical and sometimes as if instead, they belong to someone else. To assess these experiences, we designed a novel backwards masking paradigm in which participants were covertly shown their own face, masked by a stranger’s face. Participants rated feelings of familiarity associated with the strangers’ faces. 21 control participants without trauma-generated dissociation rated masks, which were covertly preceded by their own face, as more familiar compared to masks preceded by a stranger’s face. In contrast, across two samples, 28 individuals with DID and similar clinical presentations (DSM-IV Dissociative Disorder Not Otherwise Specified type 1) did not show increased familiarity ratings to their own masked face. However, their familiarity ratings interacted with self-reported identity state integration. Individuals with higher levels of identity state integration had response patterns similar to control participants. These data provide empirical evidence of aberrant self-referential processing in DID/DDNOS and suggest this is restored with identity state integration.