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Children and adolescents are more susceptible than adults to developing posttraumatic stress disorder (PTSD). Pediatric PTSD is characterized by functional alterations in brain fear circuitry, but little is known about the underlying microstructural changes; previous work has mainly focused on the corpus callosum. This study is aimed at investigating brain-wide microstructural abnormalities in pediatric PTSD, their relationship to age and sex, and their potential diagnostic value. The microstructure of major white matter tracts was assessed from diffusion tensor images acquired from 24 treatment-naive non-comorbid PTSD patients

Background: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma. Methods: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay. Results: MiR-185-5p was increased in childhood asthma patients versus HCs [median (inter-quartile range (IQR)): 2.315 (1.770–3.855) versus 1.005 (0.655–1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1β (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1β or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070–4.905) versus 1.900 (1.525–2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010). Conclusion: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients.

Brain functional network abnormalities are reported in posttraumatic stress disorder (PTSD). Most resting-state functional magnetic resonance imaging (rs-fMRI) studies have assumed that the functional networks remain static during the scan. How these might change dynamically in PTSD remains unclear.Rs-fMRI data were collected from 71 noncomorbid treatment-naïve PTSD patients and 70 demographically-matched trauma-exposed non-PTSD (TENP) controls. Network switching rate was used to characterize dynamic changes of individual resting-state functional networks. Results were analyzed by comparing switching rates between PTSD and TENP, for diagnosis-by-sex interactions, and by correlation with individual PTSD symptom severity.At the global level, PTSD showed significantly lower network switching rates than TENP. These were observed mainly in the fronto-parietal, default-mode, and limbic networks at the subnetwork level, and in the frontal and temporal regions at the nodal level. These network switching rate alterations were correlated with PTSD symptom severity. There were no significant effects of sex.These disruptions of dynamic functional network stability, reflected by lower network switching rate in the resting state, are a feature of PTSD, and suggest that the fronto-parietal, default mode and limbic networks may play a critical role in the underlying neural mechanisms.

SYHA1813 is a potent multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs)/colony-stimulating factor 1 receptor (CSF1R). This study aimed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of escalating doses of SYHA1813 in patients with recurrent high-grade gliomas (HGGs) or advanced solid tumors. This study adopted a combination of accelerated titration and a 3 + 3 design for dose escalation, with a starting dose of 5 mg once daily. The dose escalation continued at successive dose levels until the maximum tolerated dose (MTD) was determined. A total of 14 patients were enrolled and treated, including 13 with WHO grade III or IV gliomas and 1 with colorectal cancer. Two patients experienced dose-limiting toxicities (grade 4 hypertension and grade 3 mucositis oral) at 30 mg SYHA1813. The MTD was defined as 15 mg once daily. Hypertension (n = 6, 42.9%) was the most frequent treatment-related adverse event. Among evaluable patients (n = 10), 2 (20%) patients achieved partial response, and 7 (70%) had stable disease. The exposure increased with increasing doses within the studied dose range of 5 to 30 mg. Biomarker assessments demonstrated significant reductions in the levels of soluble VEGFR2 (P = .0023) and increases in the levels of VEGFA (P = .0092) and placental growth factor (P = .0484). The toxicities of SYHA1813 were manageable, and encouraging antitumor efficacy was observed in patients with recurrent malignant glioma. This study is registered with the Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx; identifier ChiCTR2100045380).

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease but still lacks a preclinical strategy to identify it. The diagnostic value of intestinal mucosal α-synuclein (αSyn) in PD has not drawn a uniform conclusion. The relationship between the alteration of intestinal mucosal αSyn expression and mucosal microbiota is unclear. Nineteen PD patients and twenty-two healthy controls were enrolled in our study from whom were collected, using gastrointestinal endoscopes, duodenal and sigmoid mucosal samples for biopsy. Multiplex immunohistochemistry was performed to detect total, phosphorylate, and oligomer α-synuclein. Next-generation 16S rRNA amplicon sequencing was applied for taxonomic analysis. The results implied that oligomer α-synuclein (OSyn) in sigmoid mucosa of PD patients was transferred from the intestinal epithelial cell membrane to the cytoplasm, acinar lumen, and stroma. Its distribution feature was significantly different between the two groups, especially the ratio of OSyn/αSyn. The microbiota composition in mucosa also differed. The relative abundances of Kiloniellales, Flavobacteriaceae, and CAG56 were lower, while those of Proteobacteria, Gammaproteobacteria, Burkholderiales, Burkholdriaceae, Oxalobacteraceae, Ralstonia, Massilla, and Lactoccus were higher in duodenal mucosa of PD patients. The relative abundances of Thermoactinomycetales and Thermoactinomycetaceae were lower, while those of Prevotellaceae and Bifidobacterium longum were higher in patients’ sigmoid mucosa. Further, the OSyn/αSyn level was positively correlated with the relative abundances of Proteobacteria, Gammaproteobacteria, Burkholderiales, Pseudomonadales, Burkholderiaceae, and Ralstonia in the duodenal mucosa, while it was negatively correlated with the Chao1 index and observed operational taxonomic units of microbiota in sigmoid mucosa. The intestinal mucosal microbiota composition of PD patients altered with the relative abundances of proinflammatory bacteria in the duodenal mucosa increased. The ratio of the OSyn/αSyn level in the sigmoid mucosa indicated a potential diagnostic value for PD, which also correlated with mucosal microbiota diversity and composition. Key points • The distribution of OSyn in sigmoid mucosa differed between PD patients and healthy controls. • Significant alterations in the microbiome were found in PD patients’ gut mucosa. • OSyn/αSyn level in sigmoid mucosa indicated a potential diagnostic value for PD.

As for the RF power supply, with the continuous expansion of the use field, the increasing integration and the substantial increase of the heat flow density in the chassis, the research on the thermal analysis and thermal design of the RF power supply is of great value. In the process of power supply development, the simulation method is used to analyze the temperature field of the power supply. The thermal design can significantly shorten the product development cycle, minimize the cost, and improve the reliability. Based on this background, this paper integrates the thermal simulation, thermal design and thermal test of RF power supply, uses thermal analysis software (Flotherm) to conduct thermal analysis of RF power supply, and conducts temperature experiment after designing internal cooling components. The experimental results show that after the thermal simulation and thermal design, the maximum internal temperature of the RF power supply is 127℃, the temperature of the key device power tube is 76.9℃, and the core temperature is 104℃, which are far below the maximum allowable temperature, meeting the thermal design requirements. This paper lays the foundation for mass manufacturing, standard formulation and serialization of RF power supply, and provides a reference for the integration of thermal analysis, thermal design and thermal test of power supply.

The idea of combining the active query strategy and the passive-aggressive (PA) update strategy in online learning can be credited to the PA active (PAA) algorithm, which has proven to be effective in learning linear classifiers from datasets with a fixed feature space. We propose a novel family of online active learning algorithms, named PAA learning for trapezoidal data streams (PAA [Formula: see text] ) and multiclass PAA [Formula: see text] (MPAA [Formula: see text] ) (and their variants), for binary and multiclass online classification tasks on trapezoidal data streams where the feature space may expand over time. Under the context of an ever-changing feature space, we provide the theoretical analysis of the mistake bounds for both PAA [Formula: see text] and MPAA [Formula: see text] . Our experiments on a wide variety of benchmark datasets have confirm that the combination of the instance-regulated active query strategy and the PA update strategy is much more effective in learning from trapezoidal data streams. We have also compared PAA [Formula: see text] with online learning with streaming features (OL [Formula: see text] )-the state-of-the-art approach in learning linear classifiers from trapezoidal data streams. PAA [Formula: see text] could achieve much better classification accuracy, especially for large-scale real-world data streams.

AtNPF4.5/AIT2, which was predicted to be a low-affinity transporter capable for nitrate uptake, was screened by ABA receptor complex in Arabidopsis ten years ago. However, the molecular and biochemical characterizations of AtNPF4.5 in plants remained largely unclear. In this study, the function of a plasma-membrane-localized and root-specifically-expressed gene MeNPF4.5 (Manihot-esculenta NITRATE TRANSPORTER 1 PTR FAMILY4.5), an ortholog of the Arabidopsis thaliana NPF4.5, was investigated in cassava roots as a nitrate efflux transporter on low nitrate medium and an influx transporter following exposure to high concentration of external nitrates. Moreover, RNA interference (RNAi) of MeNPF4.5 reduced the nitrate efflux capacity but the overexpressing cassava seedlings increased the ability of efflux from the elongation to the mature zone of root under low nitrate treatments. Besides, MeNPF4.5-RNAi expression reduced the nitrate influx capacity but enhanced nitrate absorption in parts of overexpressing plants from the meristem, elongation to mature zone of roots under high nitrate conditions. Furthermore, MeNPF4.5-RNAi seedlings survived owing to roots that could grow normally, but the MeNPF4.5-over-expressors showed adverse growth under 7% PEG6000 stress, suggesting that MeNPF4.5 negatively regulated the osmotic stress and was involved in nitrate flux through cassava seedlings.

To evaluate the association between endometriosis and adverse pregnancy outcomes.Population-based retrospective cohort study using linked universal health databases through ICES Ontario.All singleton pregnancies with an estimated date of confinement between October 2006 and February 2014.Endometriosis was determined based on a surgical and/or medical diagnosis (defined as an in-hospital admission or surgery with a diagnosis code of International Classification of Diseases [ICD]9-617 or ICD10-N80 and/or 2 medical consults billed as ICD9-617).The association between endometriosis and pregnancy outcomes was quantified by relative risks, derived using modified Poisson regression, and adjusted for maternal age, income quintiles, and history of fibroids (aRR). Mediation analysis was conducted to estimate direct effects of endometriosis diagnosis and indirect effects through mode of conception, namely: infertility without fertility treatment (known infertility but conceived without assistance), ovulation induction or intrauterine insemination, and in vitro fertilization or intracytoplasmic sperm injection, relative to unassisted conception.A total of 19,099 pregnancies had an antecedent diagnosis of endometriosis, while 768,350 did not. Mean time (standard deviation) from endometriosis diagnosis to the index pregnancy was 5.6 (4.3) years. Endometriosis was associated with an increased risk of hypertensive disorders of pregnancy (aRR, 1.09; 95% confidence interval [CI], 1.02-1.16), preterm birth37 weeks (aRR, 1.26; 95% CI, 1.20-1.33), early preterm birth34 weeks (aRR, 1.33; 95% CI, 1.17-1.50), placenta previa (aRR, 2.07; 95% CI, 1.84-2.33), placenta abruption (aRR, 1.55; 95% CI, 1.31-1.83), other placental disorders (aRR, 1.77; 95% CI, 1.36-2.30), cesarean delivery (aRR, 1.18; 95% CI, 1.16-1.21), and stillbirth (aRR, 1.32; 95% CI, 1.09-1.59). Mediation analysis suggests that endometriosis directly affects most adverse pregnancy outcomes studied, except for stillbirth where infertility diagnosis or fertility treatment indirectly accounted for part of the increased risk.Endometriosis was associated with adverse pregnancy, independent of infertility diagnosis, or fertility treatment. Future studies should investigate the mechanisms of action and potential interventions.

Alumina fabrics is a high temperature resistant textile material, and its mechanical tensile were studied in this work. The effect of fabric weaves, yarn linear densities and weft counts on the tensile breaking strength of alumina fabrics was analyzed. The results show that the tensile strength of fabric increases in the order of plain, twill, rearranged twill and satin weave. The number of interweaving points of the warp and weft yarns are the main reason for this difference. In addition, with the weft count as the invariant, when the weft count is small, the fabric strength gradually increases as the linear density of the yarn increases from 440 to 660 tex and then to 880 tex, but the growth rate gradually decreases. When the weft count increases to 7 number/1 cm, the fabric strength first increases and then decreases as the yarn linear density increased from 440 to 660 tex and then to 880 tex. When the yarn linear density is invariant, the fabric strength gradually decreases as the weft count increases from 5 to 6 to 7 number/1 cm, and the decrease rate increases gradually with the increase of the yarn linear density. The above results expose the relation between strength efficiency of warp yarn and the mechanical properties of the fabric. This study provides a theoretical basis for the weaving process of alumina fabrics.

Fiber-reinforced polymer matrix composites during engineering applications can be influenced by critical environmental conditions (e.g., water and temperature), probably causing a negative impact on the mechanical performance. In this work, the hygrothermal aging behavior and flexural property of carbon fiber (CF)-reinforced polyethylene terephthalate glycol (PETG) composites were investigated at different aging temperatures and days. The CF/PETG composites were fabricated using the hot-press molding method. The mathematical fitting model and finite element analysis method were employed to reveal the hygrothermal aging behavior and the moisture absorption evolution. After 90 days of aging, the water uptakes of the specimens at 25°C, 45°C, and 60°C are 0.55%, 0.62%, and 1.67% for PETG and 0.47%, 0.54%, and 1.52% for CF/PETG, respectively. The flexural strengths of the CF/PETG composites at 25°C, 45°C, and 60°C after 90 days of aging decrease by 28.6%, 30.2%, and 32.2% as compared with the non-aging composites, respectively. The water uptakes of the CF/PETG composites tend to increase with the increase in cyclic aging time interval. The flexural strengths of the composites with the cyclic aging intervals of 2, 5, 10, and 15 days first decrease and then increase slightly. The knowledge gained in this study will benefit future design optimization of the CF/PETG composite material and lay the foundation for its engineering application.

Glutaredoxins (GRXs) are essential for reactive oxygen species (ROS) homeostasis in responses of plants to environment changes. We previously identified several drought-responsive CC-type GRXs in cassava, an important tropical crop. However, how CC-type GRX regulates ROS homeostasis of cassava under drought stress remained largely unknown. Here, we report that a drought-responsive CC-type GRX, namely MeGRXC3, was associated with activity of catalase in the leaves of 100 cultivars (or unique unnamed genotypes) of cassava under drought stress. MeGRXC3 negatively regulated drought tolerance by modulating drought- and abscisic acid-induced stomatal closure in transgenic cassava. It antagonistically regulated hydrogen peroxide (H

Racial differences in lung cancer survival are well documented in the United States, but the fundamental causes are less clear. In this study we aimed to examine racial differences in lung cancer-specific survival (LCSS) and explore mediating factors.We used the Surveillance, Epidemiology and End Results database to obtain data pertaining to lung cancer patients from 2004 to 2017. Outcome was LCSS and covariates included nonclinical (age at diagnosis, gender, marital status, race) and clinical factors (tumor site, year of diagnosis, tumor grading, histological subtype, tumor-node-metastasis (TNM) stage, surgery status, chemotherapy status and radiation status). Kaplan-Meier methods served for comparative LCSS disparities among patients of different racial origins. Meanwhile, univariate and multivariate survival analyses were performed to determine racial disparities in LCSS.Among 61,961 lung cancer patients, 75.70% were White, 12.80% were Black, 11.30% were Asian or Pacific Islander (API), and 0.20% were American Indian/Alaska Native (AIAN). In API patients, adenocarcinoma patients (54.5%) were more frequent than in White patients (43.2%), Black patients (44.1%) and American Indian/Alaska Native patients (41.2%). Black and API patients exhibited higher stage than White patients (P0.01). However, our multivariate analysis identified API patients exhibited better LCSS than White patients (HR: 0.90, 95% CI: 0.88-0.93). Kaplan-Meier survival analysis confirmed that API patients exhibited best LCSS, especially in stage IV adenocarcinoma.The novel evidence obtained from this study enrich our knowledge of racial differences among lung cancer patients and suggest that race may be associated with LCSS.