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We investigated the phenomenon of pseudo-Hopf bifurcation in a Filippov Hindmarsh-Rose neuronal system with threshold switching, and the existence of crossing limit cycles was proved by constructing the half-return mapping. Through the threshold control, the firing state of the system could be switched, allowing transitions from a non-periodic state to a periodic state, as well as the evolution from spiking to bursting. Furthermore, through threshold switching, the system exhibited the coexistence of multiple attractors, the system could be in multiple stable states, or have multiple stable sets that could attract system trajectories. This meant that neuronal system could exhibits diverse dynamical behaviors than being limited to a single stable state. The phenomenon of period-doubling bifurcation also indicated that the system will eventually enter a chaotic state. By extending the analysis to nonlinear neuronal systems, this study contributes to a deeper understanding of complex dynamics and provides valuable insights for designing state switching in the application of neural dynamics.

Abstract We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68+ cells and FOXP3+ cells being associated with response or resistance to ICIs were also identified. In particular, CD68+ cells, CD33+ and FOXP3+ cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68dim cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.

Abstract This study investigates the craft of Tianche, an ancient towering timber structure used in well salt production in Sichuan Province, China. Originating in the Han Dynasty and maturing in the late Qing Dynasty, Tianches can reach heights of up to 110 m and represent a unique craft and structural system that is rare worldwide, yet remains largely unexplored in scholarly research. The Tianches are under threat due to a lack of maintenance and extinction of the craft. This study aims to document and elucidate the procedure and principles of the Tianche craft to help conserve this heritage. The key question is how to employ traditional craft to assemble over 100-m-tall structures from small-sized logs using pre-industrial technology. The study combines anthropological fieldwork and principles of mechanics to analyze the scientific validity and rationality of traditional crafts. The study reveals the principles of the Tianche craft, including mature craft procedure and reliable binding joints. Its advantages, namely self-locking structure, frictional force transmission, and hollow cylindrical columns, enhance the structure’s strength and stability and are fundamental for constructing 100-m-tall timber structures. Additionally, the study identifies two limitations of the craft: restricted column diameters and the tendency of the inverted dragon member’s tenon to break. This study investigated Tianche timber structures featuring hollow, bundle-like columns with frictional force transmission mechanism, presenting new possibilities beyond mainstream timber structural systems. The findings may contribute to enhancing research on the Tianche craft and could lay the foundation for future conservation practices related to Tianche heritage.

Abstract Objective Abnormalities in the gray matter structure of cerebral small vessel disease (CSVD) have been observed throughout the brain. However, whether cortico‐cortical connections exist between regions of gray matter atrophy in patients with CSVD has not been fully elucidated. This question was tested by comparing the gray matter covariance networks in CSVD patients with and without cognitive impairment (CI). Methods We performed multivariate modeling of the gray matter volume measurements of 61 patients with CI (CSVD‐CI), 85 patients without CI (CSVD‐NC), and 108 healthy controls using source‐based morphological analysis (SBM) to obtain gray matter structural covariance networks at the population level. Then, correlations between structural covariance networks and cognitive functions were analyzed in CSVD patients. Finally, a support vector machine (SVM) classifier was used with the gray matter covariance network as a classification feature to identify CI among the CSVD population. Results The results of the analysis of all the subjects showed that compared with healthy controls, the expression of the thalamic covariance network, cerebellum covariance network, and calcarine cortex covariance network was reduced in patients with CSVD. Moreover, CSVD‐CI patients showed a significant reduction in the expression of the thalamic covariance network, encompassing the thalamus and the parahippocampal gyrus, relative to CSVD‐NC patients, which persisted after excluding CSVD patients with thalamic lacunes. In patients with CSVD, cognitive functions were positively correlated with measures of the thalamic covariance network. More than 80% of CSVD patients with CI were correctly identified by the SVM classifier. Interpretation Our findings provide new evidence to explain the distribution state of gray matter reduction in CSVD patients, and the thalamic covariance network is the core region for early gray matter reduction during the development of CSVD disease, which is related to cognitive deficits. Reduced expression of thalamic covariance networks may provide a neuroimaging biomarker for the early identification of cognitive impairment in CSVD patients.

Abstract Childhood obesity not only has a negative impact on a child's health but is also a significant risk factor for adult obesity and related metabolic disorders, making it a major global public health concern. Recent studies have revealed the crucial role of gut microbiota in the occurrence and development of obesity, in addition to genetic and lifestyle factors. In this study, we recruited 19 normal-weight children and 47 children with varying degrees of obesity. A questionnaire survey was conducted to inquire about the family background, lifestyle habits and dietary composition of the 66 children. Findings indicate that fathers of obese children tend to be obese themselves, while children with highly educated mothers are more likely to maintain a normal weight. Furthermore, overweight children tend to spend more time on electronic devices and less time on physical activities compared to their normal-weight counterparts. Obese children exhibit significant differences in breakfast and dinner dietary composition when compared to children with normal weight. Additionally, the gut microbiota of these 66 children was analyzed using 16S rRNA sequencing. Analysis of gut microbiota composition showed similar compositions among children with varying degrees of obesity, but significant differences were observed in comparison to normal-weight children. Obese children exhibited a reduced proportion of Bacteroidota and an increased proportion of Firmicutes, resulting in an elevated Firmicutes/Bacteroidota ratio. Moreover, Actinobacteriota were found to be increased in the gut microbiota of children with varying degrees of obesity. PICRUSt analysis indicated significant metabolic differences in the microbiota functions between obese and normal-weight children, suggesting the composition of gut microbiota could be a crucial factor contributing to obesity. These findings provide valuable insights for the treatment of childhood obesity.

BackgroundPulmonary hypertension (PH) is a progressive disease affecting the lung vasculature that is characterized by sustained vasoconstriction and leads to vascular remodeling. The lung microbiome contributes to PH progression, but the function of the gut microbiome and the correlation between the gut microbiome and metabolome remain unclear. We have analyzed whether chronic hypoxia-induced PH alters the rat fecal microbiota.PurposeWe explored hypoxia-induced pulmonary hypertension model rats to find out the characteristic changes of intestinal microorganisms and metabolites of hypoxia-induced pulmonary hypertension, and provide a theoretical basis for clinical treatment.MethodsIn the current study, a chronic hypoxia-induced PH rat model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the occurrence and development of PH. 16S ribosomal ribonucleic acid (16S rRNA), short-chain fatty acid (SCFA) measurements, mass spectrometry (MS) metabolomics analysis and metatranscriptome were performed to analyze stool samples. The datasets were analyzed individually and integrated for combined analysis using bioinformatics approaches.ResultsOur results suggest that the gut microbiome and metabolome of chronic hypoxia-induced PH rats are distinct from those of normoxic rats and may thus aid in the search for new therapeutic or diagnostic paradigms for PH.ConclusionThe gut microbiome and metabolome are altered as a result of chronic hypoxia-induced PH. This imbalanced bacterial ecosystem might play a pathophysiological role in PH by altering homeostasis.

Background There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes.Methods Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC

Summary: Although up to 80% small cell lung cancer (SCLC) patients’ response is good for first-line chemotherapy regimen, most patients develop recurrence of the disease within weeks to months. Here, we report cytostatic effect of leflunomide (Leflu) and teriflunomide (Teri) on SCLC cell proliferation through inhibition of DRP1 phosphorylation at Ser616 and decreased mitochondrial fragmentation. When administered together, Teri and carboplatin (Carbo) act synergistically to significantly inhibit cell proliferation and DRP1 phosphorylation, reduce abundance of intermediates in pyrimidine de novo pathway, and increase apoptosis and DNA damage. Combination of Leflu&Carbo has anti-tumorigenic effect in vivo. Additionally, lurbinectedin (Lur) and Teri potently and synergistically inhibited spheroid growth and depleted uridine and DRP1 phosphorylation in mouse tumors. Our results suggest combinations of Carbo and Lur with Teri or Leflu are efficacious and underscore how the relationship between DRP1/DHODH and mitochondrial plasticity serves as a potential therapeutic target to validate these treatment strategies in SCLC clinical trials.

ObjectivesThe aims of this study were to report the effectiveness and safety of teriflunomide in Chinese patients with relapsing–remitting multiple sclerosis (RRMS) and to explore the association of paramagnetic rim lesion (PRL) burden with patient outcome in the context of teriflunomide treatment and the impact of teriflunomide on PRL burden.MethodsThis is a prospective observational study. A total of 100 RRMS patients treated with teriflunomide ≥3 months were included in analyzing drug persistence and safety. Among them, 96 patients treated ≥6 months were included in assessing drug effectiveness in aspects of no evidence of disease activity (NEDA) 3. The number and total volume of PRL were calculated in 76 patients with baseline susceptibility-weighted imaging (SWI), and their association with NEDA3 failure during teriflunomide treatment was investigated.ResultsOver a treatment period of 19.7 (3.1–51.7) months, teriflunomide reduced annualized relapse rate (ARR) from 1.1 ± 0.8 to 0.3 ± 0.5, and Expanded Disability Status Scale (EDSS) scores remained stable. At month 24, the NEDA3% and drug persistence rate were 43.8% and 65.1%, respectively. In patients with a baseline SWI, 81.6% had at least 1 PRL, and 42.1% had ≥4 PRLs. The total volume of PRL per patient was 0.3 (0.0–11.5) mL, accounting for 2.3% (0.0%–49.0%) of the total T2 lesion volume. Baseline PRL number ≥ 4 (OR = 4.24, p = 0.009), younger onset age (OR = 0.94, p = 0.039), and frequent relapses in initial 2 years of disease (OR = 13.40, p = 0.026) were associated with NEDA3 failure. The PRL number and volume were not reduced (p = 0.343 and 0.051) after teriflunomide treatment for more than 24 months. No new safety concerns were identified in this study.ConclusionTeriflunomide is effective in reducing ARR in Chinese patients with RRMS. Patients with less PRL burden, less frequent relapses, and relatively older age are likely to benefit more from teriflunomide, indicating that PRL might be a valuable measurement to inform clinical treatment decision.

BackgroundOur study aimed to develop machine learning algorithms capable of predicting red blood cell (RBC) transfusion during valve replacement surgery based on a preoperative dataset of the non-anemic cohort.MethodsA total of 423 patients who underwent valvular replacement surgery from January 2015 to December 2020 were enrolled. A comprehensive database that incorporated demographic characteristics, clinical conditions, and results of preoperative biochemistry tests was used for establishing the models. A range of machine learning algorithms were employed, including decision tree, random forest, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), support vector classifier and logistic regression (LR). Subsequently, the area under the receiver operating characteristic curve (AUC), accuracy, recall, precision, and F1 score were used to determine the predictive capability of the algorithms. Furthermore, we utilized SHapley Additive exPlanation (SHAP) values to explain the optimal prediction model.ResultsThe enrolled patients were randomly divided into training set and testing set according to the 8:2 ratio. There were 16 important features identified by Sequential Backward Selection for model establishment. The top 5 most influential features in the RF importance matrix plot were hematocrit, hemoglobin, ALT, fibrinogen, and ferritin. The optimal prediction model was CatBoost algorithm, exhibiting the highest AUC (0.752, 95% CI: 0.662–0.780), which also got relatively high F1 score (0.695). The CatBoost algorithm also showed superior performance over the LR model with the AUC (0.666, 95% CI: 0.534–0.697). The SHAP summary plot and the SHAP dependence plot were used to visually illustrate the positive or negative effects of the selected features attributed to the CatBoost model.ConclusionsThis study established a series of prediction models to enhance risk assessment of intraoperative RBC transfusion during valve replacement in no-anemic patients. The identified important predictors may provide effective preoperative interventions.

Background Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population.Methods We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB.Results NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p

Abstract Background The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. Methods Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. Results Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. Conclusions We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients.

Inhibition of AMPK leads to metabolic perturbations yet how AMPK is inactivated is not fully understood. Here the authors show protein phosphatase 6 subunit SAPS3 is a negative regulator of AMPK and loss of SAPS3 activates AMPK and protects male mice against overnutrition.

BackgroundSex-related effects have been observed in relapsing-remitting multiple sclerosis (RRMS), but their impact on functional networks remains unclear. ObjectiveTo investigate the sex-related differences in connectivity strength and time variability within large-scale networks in RRMS.MethodsThis is a multi-center retrospective study. A total of 208 RRMS patients (135 females; 37.55 ± 11.47 years old) and 228 healthy controls (123 females; 36.94 ± 12.17 years old) were included. All participants underwent clinical and MRI assessments. Independent component analysis was used to extract resting-state networks (RSNs). We assessed the connectivity strength using spatial maps (SMs) and static functional network connectivity (sFNC), evaluated temporal properties and dynamic functional network connectivity (dFNC) patterns of RSNs using dFNC, and investigated their associations with structural damage or clinical variables. ResultsFor static connectivity, only male RRMS patients displayed decreased SMs in the attention network and reduced sFNC between the sensorimotor network and visual or frontoparietal networks compared with healthy controls [P

BackgroundCoronary artery bypass grafting using radial artery grafts (RA-CABG) has improved long-term outcomes. However, major adverse cardiovascular events (MACE-4, including all-cause death, myocardial infarction, stroke, and repeat revascularization) after RA-CABG still occur and the predictors remain uncertain. This study aimed to detect independent risk factors of MACE-4 after RA-CABG.MethodsThis is a retrospective case-control study (NCT04935086) conducted among patients who underwent primary isolated RA-CABG between 2009 and 2019 in our center. Baseline characteristics, procedure characteristics, and medication use were compared to identify the independent predictors of MACE-4, all-cause death, and myocardial infarction (MI) with univariate and then multivariate logistic regression.ResultsA total of 370 patients were analyzed using a mean follow-up duration of 48.8 ± 41.0 months. MACE-4, all-cause death, and MI occurred in 102 (27.6%), 27 (7.3%), and 66 patients (17.8%), respectively. Multivariate analysis revealed prior MI (OR = 2.12, 95%CI 1.05–4.25, P = 0.04) and RA to the left anterior descending artery (LAD) (non-left internal mammary artery to LAD) (OR = 4.87, 95%CI 1.41–16.82, P = 0.01) as independent predictors of MACE-4 after surgery. Female (OR = 4.53, 95%CI 1.06–19.41, P = 0.04), left ventricular ejection fraction (LVEF)

Background and purposePrevious studies have focused on the changes of dynamic and static functional connections in cerebral small vessel disease (CSVD). However, the dynamic characteristics of local brain activity are poorly understood. The purpose of this study was to investigate the dynamic cerebral activity changes in patients with CSVD using the dynamic amplitude of low-frequency fluctuation (d-ALFF).MethodsA total of 104 CSVD patients with cognitive impairment (CSVD-CI, n = 52) or normal cognition (CSVD-NC, n = 52) and 63 matched healthy controls (HCs) were included in this study. Every participant underwent magnetic resonance imaging scans and a battery of neuropsychological examinations. The dynamics of spontaneous brain activity were assessed using dynamic changes in the amplitude of low-frequency fluctuation (ALFF) with the sliding-window method. We used voxel-wise one-way analysis of variance (ANOVA) to compare dynamic ALFF variability among the three groups. Post-hoc t-tests were used to evaluate differences between each group pair. Finally, the brain regions with d-ALFF values with differences between CSVD subgroups were taken as regions of interest (ROI), and the d-ALFF values corresponding to the ROI were extracted for partial correlation analysis with memory.Results(1) There was no significant difference in age (p = 0.120), sex (p = 0.673) and education (p = 0.067) among CSVD-CI, CSVD-NC and HC groups, but there were significant differences Prevalence of hypertension and diabetes mellitus among the three groups (p

Fish segmentation in underwater videos provides basic data for fish measurements, which is vital information that supports fish habitat monitoring and fishery resources survey. However, because of water turbidity and insufficient lighting, fish segmentation in underwater videos has low accuracy and poor robustness. Most previous work has utilized static fish appearance information while ignoring fish motion in underwater videos. Considering that motion contains more detail, this paper proposes a method that simultaneously combines appearance and motion information to guide fish segmentation in underwater videos. First, underwater videos are preprocessed to highlight fish in motion, and obtain high-quality underwater optical flow. Then, a multi-source guidance network (MSGNet) is presented to segment fish in complex underwater videos with degraded visual features. To enhance both fish appearance and motion information, a non-local-based multiple co-attention guidance module (M-CAGM) is applied in the encoder stage, in which the appearance and motion features from the intra-frame salient fish and the moving fish in video sequences are reciprocally enhanced. In addition, a feature adaptive fusion module (FAFM) is introduced in the decoder stage to avoid errors accumulated in the video sequences due to blurred fish or inaccurate optical flow. Experiments based on three publicly available datasets were designed to test the performance of the proposed model. The mean pixel accuracy (mPA) and mean intersection over union (mIoU) of MSGNet were 91.89% and 88.91% respectively with the mixed dataset. Compared with those of the advanced underwater fish segmentation and video object segmentation models, the mPA and mIoU of the proposed model significantly improved. The results showed that MSGNet achieves excellent segmentation performance in complex underwater videos and can provide an effective segmentation solution for fisheries resource assessment and ocean observation. The proposed model and code are exposed via Github1.

ObjectiveTo characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry).Materials and methodsFormalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients.ResultsPatients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p

ObjectiveTo analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC).MethodsA total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated).ResultsForty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p

Abstract This paper develops a novel integrated collision avoidance strategy for autonomous vehicles in an emergency based on steering and braking. Specifically, the framework of the collision avoidance strategy is composed of two parts: an up-level decision-making layer and a low-level controller layer. The purpose of the up-level is to select the appropriate control strategy based on the vehicle information, and the low-level is to drive the vehicle according to the instructions generated by the up-level. More concretely, a novel control strategy is proposed by integrating four-wheel steering, active rear steering, and differential braking with guaranteed path-tracking accuracy and driving stability by adaptive model predictive control (AMPC). Finally, extensive co-simulations in MATLAB/Simulink and CarSim are conducted to verify the effectiveness of the proposed collision avoidance strategy in terms of tracking error, yaw rate, and roll angle.

In the original publication [...]

We aimed to compare the performance and interobserver agreement of radiologists manually segmenting images or those assisted by automatic segmentation. We further aimed to reduce interobserver variability and improve the consistency of radiomics features. This retrospective study included 327 patients diagnosed with prostate cancer from September 2016 to June 2018; images from 228 patients were used for automatic segmentation construction, and images from the remaining 99 were used for testing. First, four radiologists with varying experience levels retrospectively segmented 99 axial prostate images manually using T2-weighted fat-suppressed magnetic resonance imaging. Automatic segmentation was performed after 2 weeks. The Pyradiomics software package v3.1.0 was used to extract the texture features. The Dice coefficient and intraclass correlation coefficient (ICC) were used to evaluate segmentation performance and the interobserver consistency of prostate radiomics. The Wilcoxon rank sum test was used to compare the paired samples, with the significance level set at p < 0.05. The Dice coefficient was used to accurately measure the spatial overlap of manually delineated images. In all the 99 prostate segmentation result columns, the manual and automatic segmentation results of the senior group were significantly better than those of the junior group (p < 0.05). Automatic segmentation was more consistent than manual segmentation (p < 0.05), and the average ICC reached >0.85. The automatic segmentation annotation performance of junior radiologists was similar to that of senior radiologists performing manual segmentation. The ICC of radiomics features increased to excellent consistency (0.925 [0.888~0.950]). Automatic segmentation annotation provided better results than manual segmentation by radiologists. Our findings indicate that automatic segmentation annotation helps reduce variability in the perception and interpretation between radiologists with different experience levels and ensures the stability of radiomics features.

Abstract Background: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume. Methods: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 0.07 kPa/L/s and LAA− 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted. Results: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87–9.27, P

In this work, a narrow-linewidth linearly polarized fiber amplifier with a record output power of 3.2 kW was achieved based on a homemade polarization-maintaining Yb-doped fiber corresponding to a slope efficiency of 79% and a 3 dB linewidth of 0.2227 nm. By examining various numerical aperture (NA) PMYDFs, the experimental investigation on expanding mode instability (MI) threshold in PM fiber amplifiers was put on display. And the results reveal that the MI threshold is enhanced by more than 370 W for every 0.004 decrease in core numerical aperture. Increasing the seed linewidth from 0.0454 nm to 0.0976 nm by adding 200 m polarization maintaining Ge-doped fiber the stimulated Brillouin scattering threshold increased from 805 W to above 3.2 kW. By applying the MI suppression method, a double-eight-shaped aluminum plate was adopted to coil the gain fiber, and the MI threshold increased by more than 1100 W.

Brain morphometric alterations involve multiple brain regions on progression of the disease in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and exhibit age-related degenerative changes during the pathological aging. Recent advance in brain morphometry as measured using MRI have leveraged Person-Based Similarity Index (PBSI) approach to assess the extent of within-diagnosis similarity or heterogeneity of brain neuroanatomical profiles between individuals of healthy populations and validate in neuropsychiatric disorders. Brain morphometric changes throughout the lifespan would be invaluable for understanding regional variability of age-related structural degeneration and the substrate of inflammatory demyelinating disease. Here, we aimed to quantify the neuroanatomical profiles with PBSI measures of cortical thickness (CT) and subcortical volumes (SV) in 263 MS, 207 NMOSD, and 338 healthy controls (HC) from six separate central datasets (aged 11–80). We explored the between-group comparisons of PBSI measures, as well as the advancing age and sex effects on PBSI measures. Compared to NMOSD, MS showed a lower extent of within-diagnosis similarity. Significant differences in regional contributions to PBSI score were observed in 29 brain regions between MS and NMOSD (P

Objective. To identify any concomitant complications other than bleeding (COTB) before and after endoscopic treatment of esophagogastric variceal bleeding (EGVB) in liver cirrhosis patients and explore the underlying risk factors. Materials and Methods. Cirrhotic patients complicated with EGVB, who underwent interventional endoscopic treatments in our hospital from November 2017 to August 2020, were enrolled in this study. Clinical data were retrospectively analyzed for COTB at admission and within 2 years of the first endoscopic treatment. Patients were screened for potential risk factors of COTB before and after the treatment. Univariate analysis was performed to identify clinical factors of secondary complications, and statistically significant factors were included in the multivariate Cox and logistic regression analyses. Results. Of the 547 patients with cirrhosis, 361 individuals had COTB in the first endoscopic treatment. In this cohort, the top 3 prevalent incidences were portal vein thrombosis (PVT) or spongiosis, cholelithiasis, and pathogenic infections. The COTB did not occur at admission in 171 liver cirrhosis patients but happened at the follow-up. Higher Child-Pugh scores indicated potential risks of multiple concurrent complications, including bleeding. Risk factors for concomitant PVT or cavernous changes after endoscopic treatment of EGVB, pathogenic infections, and cholelithiasis could prolong the cirrhosis symptoms, while noncholestatic cirrhosis patients might have a lower risk than posthepatitis B cirrhosis patients, in the context of a higher degree of EGV and serum level of D-D and a lower blood calcium level. Conclusions. Clinical treatment and interventions can be tailored to avoid other complications during and after EGVB treatment, which can affect the outcome and prognosis of bleeding symptoms.

Abstract Sorption‐based atmospheric water harvesting (AWH) offers a promising solution to the water scarcity in arid regions. However, majority of the existing AWH sorbents are suffering from rather poor water productivity due to their slow water adsorption–desorption cycling capability especially when they are applied in high packing thickness. Herein, an oxygen plasma‐treated magnetic flower‐like porous carbon (P‐MFPC) with large open surfaces, abundant surface oxygen‐containing moieties, and excellent localized magnetic induction heating (LMIH) capacity is developed. These merits, together with the use of air‐blowing‐assisted water adsorption and LMIH‐driven water desorption strategy, synergistically allow P‐MFPC with 2 cm of packing thickness to complete a AWH cycling in 20 min and deliver a record 4.5 LH2O kg−1 day−1 of water productivity at 30% relative humidity. Synergistically enabling such an ultrafast AWH cycling at high sorbent packing thickness provides a promising way for the scalable high‐yield AWH with compact AWH systems.

We presented an experimental comparison of the core-composition difference on the suppression of the photodarkening and transverse mode instability effects. Two core-composition fibers, entailing Yb/Al/Ce and Yb/Al/P co-doped fibers, were fabricated by MCVD process combined with solution doping technique. The parameters of two fibers were almost the same. The PD-induced loss at equilibrium was 3.94 dB/m at 702 nm in Yb/Al/Ce fiber, while it was 0.99 dB/m in Yb/Al/P fiber. To obtain a deeper understanding of the impact of PD on laser performance, a bidirectional pumping fiber amplifier was constructed. Compared with Yb/Al/Ce co-doped fiber, the TMI thresholds of Yb/Al/P co-doped fiber were enhanced in co-pumped and counter-pumped schemes. Meanwhile, the slope efficiency in bidirectional scheme was promoted by 4%. Moreover, the transmittance at 638 nm confirmed the superior PD resistance of Yb/Al/P co-doped fiber. These experimental results pave the way for the further development of high-power fiber lasers.

BackgroundDual antiplatelet therapy (DAPT) is recommended in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). Clopidogrel is less effective among patients with loss-of-function (LoF) of CYP2C19 alleles, while ticagrelor has direct effects on P2Y12 receptor. Whether a CYP2C19 genotype plus platelet aggregation test (PAgT)-guided DAPT after CABG could improve clinical outcomes remain uncertain.Materials and methodsFrom August 2019 to December 2020, 1,134 consecutive patients who underwent OPCAB received DAPT for 1 year after surgery in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. According to the actual treatment they received in real-world, 382 (33.7%) of them received a traditional DAPT: aspirin 100 mg qd + clopidogrel 75 mg qd, no matter the CYP2C19 genotype and response in platelet aggregation test (PAgT). The other 752 (66.3%) patients received an individual DAPT based on CYP2C19 genotype and PAgT: aspirin 100 mg qd + clopidogrel 75 mg qd if CYP2C19 was extensive metabolizer, or moderate metabolizer but normal response in PAgT; aspirin 100 mg qd + ticagrelor 90 mg bid if CYP2C19 was poor metabolizer, or moderate metabolizer but no or low response in PAgT. One-year follow-up was achieved for all patients. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. The safety outcome was thrombolysis in myocardial infarction (TIMI) criteria major bleeding.ResultsCompared with the traditional DAPT group, the risk of MACE in the individual DAPT group was significantly lower (5.5 vs. 9.2%, HR 0.583; 95% CI, 0.371–0.915; P = 0.019), mainly due to the decreased risk of MI (1.7 vs. 4.2%, HR 0.407; 95% CI, 0.196–0.846; P = 0.016). The risk of TIMI major bleeding events was similar between the two groups (5.3 vs. 6.0%, RR 0.883; 95% CI, 0.537–1.453; P = 0.626).ConclusionFor patients who underwent OPCAB, individual DAPT (CYP2C19 genotype plus PAgT-guided strategy) was associated with a lower risk of MACE and a similar risk of major bleeding.

BackgroundIntraoperative transfusion is associated with adverse clinical outcomes in cardiac surgery. However, few studies have shown the impact of intraoperative red blood cell (RBC) transfusion on non-anemic patients undergoing cardiac surgery. We assessed the in-hospital clinical outcomes of non-anemic patients undergoing isolated valve replacements and investigated the predictors associated with intraoperative RBC transfusion.MethodsWe enrolled 345 non-anemic patients undergoing isolated valve replacements in our department from January 2015 to December 2019. The patients were stratified by the receipt of intraoperative RBC transfusion. Baseline characteristics were compared between groups and multiple logistic regression was used to identify the predictors for intraoperative RBC transfusion. The association between intraoperative RBC transfusion and in-hospital outcomes was also evaluated.ResultsIntraoperative RBC transfusion developed in 84 of the 345 enrolled patients (24.3%). Three independent predictors for intraoperative RBC transfusion of non-anemic patients undergoing isolated valve replacements were identified by multivariate logistic analysis, including female, iron deficiency and hemoglobin level. When the two groups were compared, a significant tendency of higher in-hospital mortality (6.0% vs. 1.1%, P = 0.033) and higher incidence of postoperative hypoxemia (9.5% vs. 2.7%, P = 0.007) were observed in the intraoperative RBC transfusion group. After adjustment, the presence of intraoperative RBC transfusion was associated with an increase in postoperative hypoxemia (OR = 3.36, 95% CI: 1.16–9.71, P = 0.026).ConclusionIntraoperative RBC transfusion was associated with poorer clinical outcomes in non-anemic adults undergoing isolated valve replacements, which significantly increased the risk of postoperative hypoxemia. The independent predictors of intraoperative RBC transfusion, such as iron deficiency and female, were identified, which may be helpful for risk assessment and perioperative management.

A gain-enhanced 10/125 μm polarization-maintaining Yb-doped fiber (PMYDF), with the cladding absorption of 7.5 dB/m at 976 nm, for narrow linewidth linearly polarized fiber oscillator or amplifiers is presented. By utilizing the gain-enhanced PMYDF in an all-fiber laser oscillator, an output power of 123 W is achieved with applying appropriate bending strategies and thermal management, corresponding to the slope efficiency of 86.7%. By applying the gain-enhanced PMYDF in seed, an increase of 34% in the longitudinal mode interval is effectively achieved compared to the commercial PMYDF, while the number of longitudinal modes is only 75%. According to the main oscillation power amplification (MOPA) system, the total amount of spectral broadening applying the seed with the gain-enhanced PMYDF are only 67%, 64% and 54% of applying the seed with the commercial PMYDF, corresponding to co-pumping, bi-pumping and counter-pumping schemes, respectively.

We present a numerical analysis of noise performance improvement of the erbium-doped fiber amplifier by flatting the mode field intensity distribution within the interaction region of erbium ions. Three different refractive index types of erbium-doped fiber were used to study the effect of the pump mode intensity distribution on noise performance. The results show that taking advantage of the depressed refractive index erbium-doped fiber which has a flat mode distribution in the fiber core, the maximum reduction of nearly 0.53 dB for noise figure was achieved across the full C-band. Based on the center depressed refractive index profile, the noise figure was further decreased by about 0.1 dB by reducing the doping radius to 0.71 μm. Finally, maintaining the same gain level of ∼38.3 dB, a NF reduction of ∼0.63 dB was realized by introducing the center depressed refractive index profile and narrowing the erbium doping region. It is suggested that our investigation shows great potential for improving the noise performance of the erbium-doped fiber amplifier.

We propose a novel negative-curvature hollow-core fiber structure with double trigonal-symmetrical anti-resonant elements implementing single-mode or polarization-maintaining transmission for high-power laser delivery in the 1 µm wavelength window. For the single-mode fiber, the single-mode performance with a higher-order modes extinction ratio (HOMER) as high as 4.65*104 is achieved, and it remains >1*104 with a large fault tolerance proportion of tubes size, which can increase the flexibility of fiber fabrication. For another polarization-maintaining fiber, an ultra-low confinement loss of 0.005 dB/m is obtained for polarization-maintaining transmission by optimizing the refractive index of the two transverse glass tubes, while the polarization extinction ratio and HOMER remain both >1*103. This is the first birefringent negative-curvature hollow-core fiber with a loss below 0.01 dB/m in the 1 µm wavelength window.

Collision avoidance has been widely researched in the field of intelligent vehicles (IV). However, the majority of research neglects the individual driver differences. This paper introduced a novel personalized collision avoidance control (PCAC) strategy for IV based on driving characteristics (DC), which can better satisfy various scenarios and improve drivers’ acceptance. First, the driver’s DC is initially classified into four types using K-means clustering, followed by the application of the analytic hierarchy process (AHP) method to construct the DC identification model for the PCAC design. Then, a novel PCAC is integrated with a preview-follower control (PFC) module, an active rear steering (ARS) module, and a forward collision control (FCC) module to ensure individual requirements and driving stability. Moreover, simulations verified the validity of the developed PCAC in terms of path tracking, lateral acceleration, and yaw rate. The research results indicate that DC can be identified effectively through APH, and PCAC based on DC can facilitate the development of intelligent driving vehicles with superior human acceptance performance.

High-grade (WHO grades III-IV) glioma remains one of the most lethal human cancers. Adoptive transfer of tumor-targeting chimeric antigen receptor (CAR)-redirected T cells for high-grade glioma has revealed promising indications of anti-tumor activity, but objective clinical responses remain elusive for most patients. A significant challenge to effective immunotherapy is the highly heterogeneous structure of these tumors, including large variations in the magnitudes and distributions of target antigen expression, observed both within individual tumors and between patients. To obtain a more detailed understanding of immunotherapy target antigens within patient tumors, we immunochemically mapped at single cell resolution three clinically-relevant targets, IL13Rα2, HER2 and EGFR, on tumor samples drawn from a 43-patient cohort. We observed that within individual tumor samples, expression of these antigens was neither random nor uniform, but rather that they mapped into local neighborhoods – phenotypically similar cells within regions of cellular tumor – reflecting not well understood properties of tumor cells and their milieu. Notably, tumor cell neighborhoods of high antigen expression were not arranged independently within regions. For example, in cellular tumor regions, neighborhoods of high IL13Rα2 and HER2 expression appeared to be reciprocal to those of EGFR, while in areas of pseudopalisading necrosis, expression of IL13Rα2 and HER2, but not EGFR, appeared to reflect the radial organization of tumor cells around hypoxic cores. Other structural features affecting expression of immunotherapy target antigens remain to be elucidated. This structured but heterogeneous organization of antigen expression in high grade glioma is highly permissive for antigen escape, and combinatorial antigen targeting is a commonly suggested potential mitigating strategy. Deeper understanding of antigen expression within and between patient tumors will enhance optimization of combination immunotherapies, the most immediate clinical application of the observations presented here being the importance of including (wild-type) EGFR as a target antigen.

A MoNx coating serves as an effective wear protection layer and is crucial for the investigation of its tribological characteristics at various temperatures. This study examined the tribological characteristics of MoNx coatings that were deposited through high-power pulsed magnetron sputtering (HiPIMS) in an Ar/N2 environment with varying N2 partial pressures. The microstructures and mechanical properties of the coatings were elucidated using scanning electron microscopy, grazing-incidence-angle X-ray diffraction, energy-dispersive spectroscopy, and nanoindentation. The dry friction performances of the coatings at different heating temperatures were studied using a ball-on-disk tribometer. The MoNx coating produced by HiPIMS was composed primarily of fcc−Mo2N and featured a fine, dense column crystal with a maximum hardness of 28.8 GPa. The MoNx coatings exhibited excellent lubrication and wear reduction properties at room temperature (RT). The dry friction performances of the MoNx coatings at elevated temperatures were expected to depend on the growth of the MoO3 tribolayer. At relatively low temperatures (300 °C and 400 °C), the MoO3 tribolayer grew slowly and was not enough to provide good lubrication, causing increases in the dry friction of the coatings. However, the δ−MoN phase formed in the MoNx coating deposited at a high N2 partial pressure could facilitate the formation of MoO3 and thus decreased the friction coefficient at 400 °C. At the relatively high heating temperature of 500 °C, however, the MoO3 tribolayer grew so rapidly that the oxide layer became thick, resulting in an increase in the wear rate. It is believed that tuning the growth rate of MoO3 via optimizing the composition and structure of the MoNx coatings might be a useful way to improve the dry friction at various elevated temperatures.

Genes that participate in the degradation or isolation of glyphosate in plants are promising, for they endow crops with herbicide tolerance with a low glyphosate residue. Recently, the aldo-keto reductase (AKR4) gene in Echinochloa colona (EcAKR4) was identified as a naturally evolved glyphosate-metabolism enzyme. Here, we compared the glyphosate-degradation ability of theAKR4 proteins from maize, soybean and rice, which belong to a clade containing EcAKR4 in the phylogenetic tree, by incubation of glyphosate with AKR proteins both in vivo and in vitro. The results indicated that, except for OsALR1, the other proteins were characterized as glyphosate-metabolism enzymes, with ZmAKR4 ranked the highest activity, and OsAKR4-1 and OsAKR4-2 exhibiting the highest activity among the AKR4 family in rice. Moreover, OsAKR4-1 was confirmed to endow glyphosate-tolerance at the plant level. Our study provides information on the mechanism underlying the glyphosate-degradation ability of AKR proteins in crops, which enables the development of glyphosate-resistant crops with a low glyphosate residue, mediated by AKRs.

Machine learning (ML) methods were developed and optimized for description and understanding a physical separation process. Indeed, this work indicates application of machine learning technique for a real physical system and optimization of process parameters to achieve the target. A bunch of datasets were extracted from resources for physical adsorption process in removal of impurities from water as a case study to test the developed machine learning model. The case study process is adsorption process which has extensive application in science and engineering. The machine learning (ML) method was developed, and the parameters were optimized in order to get the best simulation’s performance for adsorption process. The data are used to correlate the adsorption capacity of the material to the adsorption parameters including dosage and solution pH. Randomized training and validation were performed to predict the process’s output, and great agreement was obtained between the predicted values and the observed values with R2 values greater than 0.9 for all cases of training and validation at the optimum conditions. Three different machine learning techniques including Random Forest (RF), Extra Tree (ET), and Gradient Boosting (GB) were employed for the adsorption data. Quantitatively, R2 scores of 0.958, 0.998, and 0.999 were obtained for RF, GB, and ET, respectively. It was indicated that GB and ET models performed almost the same and better than RF in prediction of adsorption data.

Background and ObjectivesAccumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality.MethodsWe measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality.ResultsA total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35–12.95, p < 0.001].ConclusionLower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

The remarkable evolution of ytterbium-doped fiber (YDF) lasers and amplifiers is interrupted by a limiting thermo-optical effect called transverse mode instability (TMI). Hereon, we propose a Gaussian-shaped gain-dopant distributed (GSGDD) YDF, which is fabricated by a modified chemical vapor deposition (MCVD) process combined with solution doping technique (SDT). By regulating the solution concentrations of soot layers, the content of Yb3+ ions presents Gaussian-shaped distribution in the transverse direction while the refractive index profile (RIP) exhibits a stepped profile. The laser performance of this fiber is verified by a bidirectional pumped master oscillator power amplifier (MOPA). Over 3 kW near-single-mode laser output is obtained with the slope efficiency of 84.9%. At the highest power output, there are no Stokes light components in the spectrum and the beam quality M2 factor is ∼1.45 These results suggest that the GSGDD fiber owns great potential to achieve high power output with excellent beam quality.

BackgroundChronic bronchitis in patients with chronic obstructive pulmonary disease (COPD) is associated with poor respiratory health outcomes. However, controversy exists around whether non-obstructive chronic bronchitis (NOCB) is associated with airflow obstruction, lung function decline, and all-cause mortality in ever smoker or never smoker.Research QuestionThis systematic review and meta-analysis aimed to clarify the relationship between NOCB and incident COPD, lung function decline, and all-cause mortality, and to quantify the magnitude of these associations.Study Design and MethodsWe searched PubMed, Embase, and Web of Science for studies published up to October 1, 2021. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD, lung function decline, and all-cause mortality in normal spirometry with and without chronic bronchitis. The primary outcomes were incident COPD and all-cause mortality. The secondary outcomes were respiratory disease-related mortality and lung function decline. Pooled effect sizes and 95% confidence intervals (CIs) were calculated using the random-effects model.ResultsWe identified 17,323 related references and included 14 articles. Compared with individuals without NOCB, individuals with NOCB had an increased risk of incident COPD (odds ratio: 1.98, 95% CI: 1.21–3.22, I2 = 76.3% and relative risk: 1.44, 95%CI: 1.13–1.85, I2 = 56.1%), all-cause mortality (hazard ratio [HR]: 1.38, 95%CI: 1.26–1.51, I2 = 29.4%), and respiratory disease-related mortality (HR: 1.88, 95%CI: 1.37–2.59, I2 = 0.0%). Data on the decline in lung function could not be quantitatively synthesized, but the five articles that assessed the rate of decline in lung function showed that lung function declines faster in individuals with NOCB. The mean difference in the additional decline in forced expiratory volume in 1 s ranged from 3.6 to 23.2 mL/year.InterpretationIndividuals with NOCB are at a higher risk of incident COPD and all-cause mortality than individuals without NOCB, highlighting the crucial need for strategies to screen for and reduce NOCB risk.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/ PROSPERO, identifier CRD42020202837

Transition metal nitrides (TMN) have received widespread consideration as supercapacitor materials for a variety of energy storage applications. An important requirement to such electrode materials is a very high specific surface area, which is typically obtained through a percolating pore-network. Here, we use arc ion plating to prepare CrN-Ni composite coatings with 0, 30.4, 54.2, and 77.6 at.% Ni. Detailed X-ray diffraction and X-ray photoelectron spectroscopy showed that the coatings consist of CrN phases next to metallic Ni. Post-deposition treatments with HCl solutions lead to selective leaching, causing a porous nanostructure for the Ni-containing CrN coatings. From there, the coating with 54.2 at.% Ni in its as-deposited state provided the highest (electrode-geometric-area)-specific capacitance after the HCl treatment, giving 58.5 mF·cm−2 at 1.0 mA·cm−2 in a 0.5 M H2SO4 aqueous electrolyte. This value is about 80 times higher than for the as-deposited coatings or the Ni-free CrN. Consequently, our strategy to combine TMNs with metallic Ni and its subsequent treatment with HCl is highly effective in enlarging the specific surface area and adsorption sites. It allows to significantly enhance the energy storage performance of TMN thin film supercapacitors.

The availability of nutrients within the tumour microenvironment can influence tumour growth. Here, the authors find that, in a melanoma mouse model, mice fed a high glutamine diet have reduced tumour growth, increased sensitivity to Braf inhibitors and elevated a-ketoglutarate levels.

We experimentally demonstrated a novel repetition rate adjustable SBS-based Q-switched fiber laser. An inserted Fabry-Perot interferometer formed by two non-contact end faces of two FC/PC fiber connectors was inserted to help the system stabilize the random output of SBS-based Q-switching. By mechanically fine-tuning the length of the inserted Fabry-Perot interferometer, a linear and continuous repetition rate adjustment under a fixed pump power was achieved. This method paves a new way for the indirect control of repetition rate in SBS-based Q-switched fiber lasers. It is also found out that higher pump power allows wider adjustment range. At 600 mW pumping which is highest pump power of the source, the repetition rate almost tripled from 11.22 kHz to 32.06 kHz only by varying the length of FP cavity in less than 3 μm. In the meantime, the variation of pulse width, output power and single pulse energy were recorded and analyzed under different fixed pump powers. Although the adjusting range of repetition rate is not very wide but the tuning of repetition rate due to such a small length changing is unique and valuable. This original repetition rate control technique has great potential in areas like environment sensing and material detections.

The human head pose estimation is an important and challenging problem, which provides the estimation of the head posture in 3D space from 2D image. It is a crucial technique for face recognition, gaze estimation, facial attribute recognition, etc. However, fast head pose estimation executing on the terminal for video edge computation has many challenges due to the computational complexity of the existing algorithms. In this paper, we propose a fast head pose estimation method based on a novel Rotation-Adaptive facial landmark detection powered by Local Binary Feature (RALBF). The landmark detection method is structured through fusing the prior of the rotation information provided by the Progressive Calibration Networks (PCN) face detector to a Local Binary Feature (LBF) based landmark detection method, which improves the robustness against head pose variations and simultaneously keep the computing efficiency. RALBF is trained and tested on 300W dataset and AFLW2000 dataset, it is verified by the accuracy evaluation that RALBF performs better than LBF. To improve the speed of head pose estimation, the 68, 51 and 10 landmarks distribution schemes are explored and compared on speed and accuracy. In the 10 landmarks scheme, the head pose estimation running once only takes 8.3ms on Intel i7-6700HQ CPU and takes 21.8ms on HiSilicon SoC Hi3519AV100, and the average error of Euler angle is 5.9973° when the face yaw angle is between ±35° on AFLW2000 3D dataset. Experiments demonstrate our approach performing well on real scenes.

Aiming at the issue of active obstacle avoidance control for intelligent vehicles under emergency, an active safety collaborative control system integrated with adaptive cruise control (ACC), rear steering control (RSC), and rollover braking control (RBC) is developed. The proposed novel control architecture consists of a supervisor, an upper controller, and a lower controller. The supervisor decides which control mode to be used based on multi-sensors information of the driving vehicle. Active rear wheel steering based on lateral acceleration feedback and active braking control strategies based on fuzzy PID are added into the control model to enhance driving stability. To make the vehicle motion control model suitable for highway path tracking with obstacle avoidance under emergency, a priority is given to the RBC controller even though the vehicle speed is lower than the expected speed when the rollover index exceeds the safety threshold. A nonlinear vehicle simulation model is established to validate the proposed control scheme based on Carsim. Finally, a Carsim-Simulink co-simulation model is constructed, and simulation results show that the proposed integrated control strategy based on active safety collaborative control has good performance in both path tracking and driving stability, and has better stability of rollover under emergency.

Background: The molecular and clinical features of KRAS-mutated lung cancer patients treated with immunotherapy have yet to be characterized, which could guide the development of therapeutics targeting KRAS with potential immuno-oncology treatment combinations. Research Question: Do KRAS-mutated patients with different subtypes and comutations have different clinical responses and overall survival (OS) to checkpoint inhibitors? Study Design and Methods: 87 patients with NSCLC at the City of Hope who received immune checkpoint inhibitors were identified and analyzed retrospectively. Tumor genomic alterations were extracted from the clinical data with next-generation sequencing using various platforms. Demographic, clinical, molecular, and pathological information was collected with the approval of the institutional review board of the City of Hope. OS was calculated if it was available at the study time point, and responses were determined according to the RECIST v1.1. Results: Among 87 patients, 32 had a KRAS G12C mutation (36.8%), 19 had G12V (21.9%), 18 had G12D (20.7%), 6 had G12A (6.9%), 3 had G12R (3.45%), and 10 had amplification (11.49%) and other uncommon mutations. G12D had a statistically significant Odds Ratio (OR) between patients who had responses and progression of the disease (OR (95% CI) = 0.31 (0.09–0.95), p < 0.05), with 5 G12D-mutated patients having responses and 11 G12D-mutated patients having progression of the disease. In the univariate analysis with OS, there was a trend of better OS in the G12D-mutated patients, with no statistically significant difference in terms of OS between the patients who had G12D mutation and the patients who had other KRAS mutations (HR (95% CI) = 0.53 (0.21–1.36), p = 0.185). The median OS was significantly worse with KRAS comutation CDKN2A/B loss (4.2 vs. 16.9 months, HR = 3.07 (1.09–8.69), p < 0.05) and MET (3.4 vs. 17 months, HR = 3.80 (1.44–10.05), p < 0.01), which were included for the multivariate analysis. The OS with other KRAS comutations was not statistically significant, including STK11 and KEAP1. Conclusion: KRAS mutation subtypes such as G12D and comutations such as CDKN2/A and MET may modulate the immunotherapy responses and outcomes in lung cancer.

Microglia play an important role in neurodegenerative disease [i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS)]. These diseases share some similar pathological changes and several microglia-associated processes, including immune response, neuroinflammation, phagocytosis, elimination of synapses et al. Microglia in the central nervous system (CNS) has been described as having both destructive and protective effects in neurological disorders. Besides, considerable evidence also indicates that microglia play a significant role in neurogenesis, neuronal cell death, and synaptic interactions. The communication between microglia and neurons is of vital role in regulating complex functions which are key to appropriate the activity of the brain. Accumulating studies have also demonstrated that exosomes with sizes ranging from 40–100 nm, released by microglia, could serve as key mediators in intercellular signaling. These exosomes, identified in terms of cellular origin in many kinds of biological fluids, exert their effects by delivering specific cargos such as proteins, microRNAs (miRNAs), and mRNAs. It was shown that microglial exosomes could transport to and be uptake by neurons, which may either be beneficial or instead, detrimental to CNS diseases. The focus of this review is to summarize the involvement of microglial exosomes in critical pathologies associated with neurodegenerative disease and how they contribute to these disorders, including PD, AD, and ALS. We also review the application of microglia exosomes as potential biomarkers in monitoring disease progression, as well as focusing on their roles as drug delivery vehicles in treating neurodegenerative disorders.

The turbine rotor is the key component of the turbine, which has a great impact on the construction cost and power generation efficiency of an entire hydropower station. Receiving the torque of the runner transmission and completing the specified power generation is its main function. There are many uncertain factors in the design, manufacture, and operation environment of a turbine rotor. Therefore, it is necessary to optimize the mechanism on the premise of ensuring that the mechanical system meets high reliability and high safety levels. This article uses the multidisciplinary reliability analysis and optimization method under random and interval uncertainty to quantitatively analyze the uncertainty factors, and then optimally solves the RBMDO problem of the turbine rotor mechanism. Through the finite element simulation analysis of the optimized design scheme, the rationality and feasibility of the obtained results are further verified.