Kerrborch2972
Using tumor microenvironment-associated gene expression profiling, we identified that m96cl elevates the interleukin-2 (IL2) signaling pathway and results in increased IL2-mediated paracrine stimulation of CD8+ CTLs. Furthermore, we identified that the m96cl modulates the expression of IL2 in cancer cells by regulating the expression of transcriptional repressors Foxf2 and Zeb1, and thereby alters the levels of secreted IL2 in the tumor microenvironment. Last, we show that in vivo depletion of IL2 abrogates m96cl-mediated activation of CD8+ CTLs and results in loss of metastatic suppression. Therefore, we have identified a novel mechanistic role of the m96cl in the suppression of lung cancer growth and metastasis by inducing an IL2-mediated systemic CD8+ CTL immune response.
A line of evidence has shown that childhood trauma and patterns of H-shaped sulci in the orbitofrontal cortex (OFC) are associated with cognitive deficits in patients with schizophrenia. Studies have also suggested that childhood trauma is associated with OFC volumetrics. This study investigated the interrelationship between childhood trauma, OFC H-shaped sulci volume and cognitive function in patients with first-episode schizophrenia. We hypothesized that OFC H-shaped sulci volume would mediate the relationship between childhood trauma and cognitive function in patients with first-episode schizophrenia.
We recruited patients with first-episode schizophrenia (
= 63) and healthy controls (
= 48), and quantified OFC H-shaped sulci volumes with 3.0 T high-resolution MRI. We assessed cognitive function and childhood trauma experiences using the MATRICS Consensus Cognitive Battery (MCCB) and the Childhood Trauma Questionnaire (CTQ).
Patients with first-episode schizophrenia had smaller left OFC H-shaped ma might contribute to cognitive deficits in patients with first-episode schizophrenia by affecting left OFC H-shaped sulci volume. This finding can help in the design of strategies to improve cognitive function in patients with first-episode schizophrenia.
Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dysconnectivity in treatment-resistant MDD by concurrently measuring the following microglial activity with [
F]N-2-(fluoroethoxyl)benzyl-N-(4phenoxypyridin-3-yl)acetamide ([
F]FEPPA) positron emission tomography (PET); the severity of MDD; and functional or structural connectivity among insula or sgACC nodes.
Twelve patients with treatment-resistant MDD (8 female, 4 male; mean age ± standard deviation 54.9 ± 4.5 years and 23 healthy controls (11 female, 12 male; 60.3 ± 8.5 years) completed a hybrid [
F]FEPPA PET and MRI acquisition. From these, we extracted relative standardized uptake values for [
F]FEPPA activity and Pearson
-to-
scores representing functional conne depression and related to increased microglial activity in MDD.
We present preliminary evidence linking a network-level dysfunction relevant to the pathophysiology of depression and related to increased microglial activity in MDD.
Use of traditional medicine (TM) is widespread in sub-Saharan Africa as a treatment option for a wide range of disease. We aimed to describe main characteristics of TM users and estimate the association of TM use with control of hypertension.
We used data on 2128 hypertensive patients of a cross-sectional study (convenience sampling), who attended cardiology departments of 12 sub-Saharan African countries (Benin, Cameroon, Congo, Democratic Republic of the Congo, Gabon, Guinea, Côte d'Ivoire, Mauritania, Mozambique, Niger, Senegal, Togo). To model association of TM use with odds of uncontrolled, severe and complicated hypertension, we used multivariable mixed logistic regressions, and to model the association with blood pressure (systolic (SBP) and diastolic (DBP)) we used mixed linear models. All models were adjusted for age, sex, wealth, adherence to hypertension conventional treatment and country (random effect).
A total of 512 (24%) participants reported using TM, varying across countries from 10% ily within the conventional healthcare.
To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy.
We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. LCL161 in vivo All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy.
There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the ponse to prior chemotherapy.
To describe regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP).
Retrospective cohort study of a large, US commercial managed care plan claims database with pharmacy coverage from 2008 to 2018. Singleton pregnancies with at least one prior spontaneous preterm birth (sPTB) were included. Regional and state-based differences in 17-OHP use were compared. Data were analyzed using t-tests and Fisher's exact tests.
Of the 4,514 individuals with an indication for 17-OHP, 580 (12.8%) were prescribed 17-OHP. Regional and state-based differences in 17-OHP utilization were identified; Northeast 15.7%, Midwest 13.7%, South 12.0%, and West 10.4% (p=0.003).
While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.
While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.LiNi0.88Co0.1Al0.02O2 (NCA) is attractive for high-energy batteries, but phase transition and side reactions leave large volume change and thermal runaway. In order to address the drawbacks, orthorhombic Al2(WO4)3, a cheap anisotropic negative thermal expansion material, was synthesized and adopted to modify NCA, and its effects on the electrochemical performance and safety of NCA were investigated using multifarious techniques. Al2(WO4)3 can greatly improve the rate performance, cyclability at different temperatures, thermal stability, and interface behavior and intensify charge transfer as well as decline the deformation and side reactions of NCA. The discharge capacity of the NCA modified with 5 wt % Al2(WO4)3 reaches 170.0 mA h/g at 5.0 C and 25 °C. After 100 cycles, the values of this electrode at 1.0 C and 25 °C and at 3.0 C and 60 °C are 164.2 and 148.7 mA h/g, respectively, much higher than those of the pure NCA under the same conditions. Moreover, Al2(WO4)3 declines the byproducts and cation mixing and decreases the released heat, strain, and charge-transfer resistance after cycles of NCA about 37.1, 33.0, and 32.8%, respectively. The improvement mechanism is discussed. It opens an effective avenue for the applications of energy materials by simultaneously adjusting heat, structure, interface, and deformation.Copper oxide nanoparticles (CuO NPs) are widely used as fungicides in agriculture. Arsenic (As) is a ubiquitous contaminant in paddy soil. The present study was focused on the adsorption behavior of CuO NPs with regard to As as well as the characteristics of the microbial community changes in As-contaminated soil-rice systems in response to CuO NPs. The study found that CuO NPs could be a temporary sink of As in soil; a high dose of CuO NPs promoted the release of As from crystalline iron oxide, which increased the As content in the liquid phase. The study also found that the As bioavailability changed significantly when the dose of CuO NPs was higher than 50 mg kg-1 in the soil-rice system. The addition of 100 mg kg-1 CuO NPs increased the microbial diversity and the abundance of genes involved in As cycling, decreased the abundance of Fe(III)-reducing bacteria and sulfate-reducing genes, and decreased As accumulation in grains. Treatment with 500 mg kg-1 CuO NPs increased the abundance of Fe(III)-reducing bacteria and sulfate-reducing genes, decreased Fe plaques, and increased As accumulation in rice. The adverse effects of CuO NPs on crops and associated risks need to be considered carefully.The "Swiss army knife" composite density functional electronic-structure method r2SCAN-3c (J. Chem. Phys. 2021, 154, 064103) is extended and optimized for the use with Slater-type orbital basis sets. The meta generalized-gradient approximation (meta-GGA) functional r2SCAN by Furness et al. is combined with a tailor-made polarized triple-ζ Slater-type atomic orbital (STO) basis set (mTZ2P), the semiclassical London dispersion correction (D4), and a geometrical counterpoise (gCP) correction. Relativistic effects are treated explicitly with the scalar-relativistic zeroth-order regular approximation (SR-ZORA). The performance of the new implementation is assessed on eight geometry and 74 energy benchmark sets, including the extensive GMTKN55 database as well as recent sets such as ROST61 and IONPI19. In geometry optimizations, the STO-based r2SCAN-3c is either on par with or more accurate than the hybrid density functional approximation M06-2X-D3(0)/TZP. In energy calculations, the overall accuracy is similar to the original implementation of r2SCAN-3c with Gaussian-type atomic orbitals (GTO), but basic properties, intermolecular noncovalent interactions, and barrier heights are better described with the STO approach, resulting in a lower weighted mean absolute deviation (WTMAD-2(STO) = 7.15 vs 7.50 kcal mol-1 with the original method) for the GMTKN55 database. The STO-optimized r2SCAN-3c outperforms many conventional hybrid/QZ approaches in most common applications at a fraction of their cost. The reliable, robust, and accurate r2SCAN-3c implementation with STOs is a promising alternative to the original implementation with GTOs and can be generally used for a broad field of quantum chemical problems.
