Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends ...testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
Abstract Background Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory ...exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation. Materials and Methods Lyophilised aliquots of a RP along with 3 plasmas (P1 = normal; P2 = hypo-; P3 = hypercoagulable) were sent to 34 laboratories (corresponding to 38 instruments). CAT was studied using 1 and 5 pM tissue factor and other dedicated reagents. Normalisation with the local RP in use in the laboratory could also be performed. Interlaboratory CVs were calculated for each plasma before and after normalisation. Results Regarding endogenous thrombin potential, a good discrimination between the 3 plasmas was achieved in all laboratories but there was no overlap after normalisation only. CVs were generally not reduced with the use of local RP but were generally improved with normalisation using the external RP, often becoming lower than 10%. Regarding P2 however, the benefit of normalisation was poor, and there were analytical difficulties as well, some laboratories being unable to get a useable signal. Conclusions We confirm that normalisation of CAT results with a suitable external RP is useful in “real life” practice as it often permits an acceptable level of interlaboratory variability. In case of frank hypocoagulability, further improvements are required to get reliable, potentially clinically relevant results.
Establishing the appropriate theoretical framework for unconventional superconductivity in the iron-based materials requires correct understanding of both the electron correlation strength and the ...role of Fermi surfaces. This fundamental issue becomes especially relevant with the discovery of the iron chalcogenide superconductors. Here, we use angle-resolved photoemission spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44, monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these superconductors are all strongly correlated, with an orbital-selective strong renormalization in the dxy bands despite having drastically different Fermi surface topologies. Furthermore, raising temperature brings all three compounds from a metallic state to a phase where the dxy orbital loses all spectral weight while other orbitals remain itinerant. These observations establish that iron chalcogenides display universal orbital-selective strong correlations that are insensitive to the Fermi surface topology, and are close to an orbital-selective Mott phase, hence placing strong constraints for theoretical understanding of iron-based superconductors.
Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin‐like growth factor (IGF2) and hepatocyte growth ...factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high‐grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co‐injection model, we observed that FF co‐injection induced tumorigenesis of STIC‐mimicking cells, FE25. Co‐injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co‐injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring‐independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine‐protein kinase Met (cMET)/mitogen‐activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF‐IGF2 could mediate clonogenicity and stemness activities via the IGF‐1R/AKT/mammalian target of rapamycin and IGF‐1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF‐sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.
Regulatory focus theory (Higgins, 1997) has received growing attention in organizational psychology, necessitating a quantitative review that synthesizes its effects on important criteria. In ...addition, there is need for theoretical integration of regulatory focus theory with personality research. Theoretical integration is particularly relevant, since personality traits and dispositions are distal factors that are unlikely to have direct effects on work behaviors, yet they may have indirect effects via regulatory focus. The current meta-analysis introduces an integrative framework in which the effects of personality on work behaviors are best understood when considered in conjunction with more proximal motivational processes such as regulatory focus. Using a distal-proximal approach, we identify personality antecedents and work-related consequences of regulatory foci in a framework that considers both general and work-specific regulatory foci as proximal motivational processes. We present meta-analytic results for relations of regulatory focus with its antecedents (approach and avoid temperaments, conscientiousness, openness to experience, agreeableness, self-esteem, and self-efficacy) and its consequences (work behaviors and attitudes). In addition to estimates of bivariate relationships, we support a meta-analytic path model in which distal personality traits relate to work behaviors via the mediating effects of general and work-specific regulatory focus. Results from tests of incremental and relative validity indicated that regulatory foci predict unique variance in work behaviors after controlling for established personality, motivation, and attitudinal predictors. Consistent with regulatory focus theory and our integrative theoretical framework, regulatory focus has meaningful relations with work outcomes and is not redundant with other individual difference variables.
The metallic interface between insulating LaAlO3 and SrTiO3 opens up the field of oxide electronics. With more than a decade of researches on this heterostructure, the origin of the interfacial ...conductivity, however, remains unsettled. Here we resolve this long-standing puzzle by atomic-scale observation of electron-gas formation for screening hidden lattice instabilities, rejuvenated near the interface by epitaxial strain. Using atomic-resolution imaging and electron spectroscopy, the generally accepted notions of polar catastrophe and cation intermixing for the metallic interface are discounted. Instead, the conductivity onset at the critical thickness of 4-unit cell LaAlO3 on SrTiO3 substrate is accompanied with head-to-head ferroelectric-like polarizations across the interface due to strain-rejuvenated ferroelectric-like instabilities in the materials. The divergent depolarization fields of the head-to-head polarizations cast the interface into an electron reservoir, forming screening electron gas in SrTiO3 with LaAlO3 hosting complementary localized holes. The ferroelectric-like polarizations and electron-hole juxtaposition reveal the cooperative nature of metallic LaAlO3/SrTiO3.
The functionalization of C(sp3)−H bonds streamlines chemical synthesis by allowing the use of simple molecules and providing novel synthetic disconnections. Intensive recent efforts in the ...development of new reactions based on C−H functionalization have led to its wider adoption across a range of research areas. This Review discusses the strengths and weaknesses of three main approaches: transition‐metal‐catalyzed C−H activation, 1,n‐hydrogen atom transfer, and transition‐metal‐catalyzed carbene/nitrene transfer, for the directed functionalization of unactivated C(sp3)−H bonds. For each strategy, the scope, the reactivity of different C−H bonds, the position of the reacting C−H bonds relative to the directing group, and stereochemical outcomes are illustrated with examples in the literature. The aim of this Review is to provide guidance for the use of C−H functionalization reactions and inspire future research in this area.
The targeted functionalization of C(sp3)−H bonds streamlines chemical synthesis and allows the use of simple starting materials. This Review discusses the strength and weakness of the three main approaches: transition‐metal‐catalyzed C−H activation, 1,n‐hydrogen atom transfer, and transition‐metal‐catalyzed carbene/nitrene transfer.
•Epilepsy was associated with an increased risk of depression.•Epilepsy was associated with an increased risk of depression among adolescents.•Epilepsy was associated with an increased risk of ...depression among adults.
Recent studies provided inconsistent evidence for the association between epilepsy and risk of depression.
We searched for articles published in the databases (Web of Science, Google Scholar and PubMed) and before December 2021. We used STATA 12.0 software to compute odds ratios (ORs)/relative risks (RRs) and their 95% confidence intervals (CIs).
The meta-analysis indicated that epilepsy was associated with an increased risk of depression with a random effects model (OR/RR = 2.05; 95% CI: 1.77-2.37, I2 = 37.7%, p = 0.036). Subgroup studies indicated that epilepsy was associated with an increased risk of depression in both case-control and cohort studies (case-control studies: OR = 2.32; 95% CI: 1.91-2.82; cohort studies: RR = 1.71; 95% CI: 1.53-1.92). Subgroup studies indicated that epilepsy was associated with an increased risk of depression in Asian, African and Caucasian populations (Asian: OR/RR = 2.42; 95% CI: 1.48-3.95; African: OR/RR = 2.48; 95% CI: 1.88-3.28; Caucasian: OR/RR = 1.86; 95% CI: 1.60-2.15). Subgroup studies showed that epilepsy was associated with an increased risk of depression among adolescents and adults (adolescents: OR/RR = 2.54; 95% CI: 1.86-3.46; adults: OR/RR = 2.22; 95% CI: 1.79-2.75).
Epilepsy is at increased risk of depression comorbidity.
Large quantities of veterinary antibiotics (VAs) are being used worldwide in agricultural fields through wastewater irrigation and manure application. They cause damages to the ecosystem when ...discharged into the environment, but there is a lack of information on their toxicity to plants and animals. This study evaluated the phytotoxic effects of five major VAs, namely tetracycline (TC), sulfamethazine (SMZ), norfloxacin (NOR), erythromycin (ERY) and chloramphenicol (CAP), on seed germination and root elongation in lettuce, tomato, carrot and cucumber, and investigated the relationship between their physicochemical properties and phytotoxicities. Results show that these compounds significantly inhibited root elongation (p<0.05), the most sensitive endpoint for the phytotoxicity test. TC was associated with the highest level of toxicity, followed by NOR, ERY, SMZ and CAP. Regarding crop species, lettuce was found to be sensitive to most of the VAs. The median effect concentration (EC50) of TC, SMZ, NOR, ERY and CAP to lettuce was 14.4, 157, 49.4, 68.8 and 204mg/L, respectively. A quantitative structure-activity relationship (QSAR) model has been established based on the measured data. It is evident that hydrophobicity was the most important factor governing the phytotoxicity of these compounds to seeds, which could be explained by the polar narcosis mechanism. Lettuce is considered a good biomarker for VAs in the environment. According to the derived equation, phytotoxicities of selected VA compounds on different crops can be calculated, which could be applicable to other VAs. Environmental risks of VAs were summarized based on the phytotoxicity results and other persistent factors.
•Root elongation was a sensitive endpoint in the phytotoxicity test for VAs.•Among the VAs tested, TC was the most toxic compound to the crops.•Hydrophobicity was a crucial factor affecting the phytotoxic effects of VAs.•Lettuce was the most sensitive species and suggested for use as an indicator crop.
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