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Objective: This study aimed to investigate the value of artificial intelligence (AI) for distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with subsolid nodules (SSNs). Materials and methods: This retrospective study included 110 consecutive patients with 120 SSNs. The qualitative and quantitative imaging characteristics of SSNs were extracted automatically using an artificially intelligent assessment system. Then, radiologists had to verify these characteristics again. We split all cases into two groups: non-IA including 11 Atypical adenomatous hyperplasia (AAH) and 25 adenocarcinoma in situ (AIS) or IA including 7 minimally invasive adenocarcinoma (MIA) and 77 invasive adenocarcinoma (IAC). Variables that exhibited statistically significant differences between the non-IA and IA in the univariate analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) analyses were conducted to determine the cut-off values and their diagnostic performances. Results: Multivariate logistic regression analysis showed that the major diameter (odds ratio [OR] = 1.38; 95 % confidence interval [CI], 1.02–1.87; P = 0.036) and entropy of three-dimensional(3D) CT value (OR = 3.73, 95 % CI, 1.13–2.33, P = 0.031) were independent risk factors for adenocarcinomas. The cut-off values of the major diameter and the entropy of 3D CT value for the diagnosis of invasive adenocarcinoma were 15.5 mm and 5.17, respectively. To improve the classification performance, we fused the major diameter and the entropy of 3D CT value as a combined model, and the (AUC） of the model was 0.868 (sensitivity = 0.845, specificity = 0.806). Conclusion: The major diameter and entropy of 3D CT value can distinguish non-IA from IA. AI can improve performance in distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with SSNs.

Background Standard first-line therapies for metastatic colorectal cancer (mCRC) include fluoropyrimidine-containing regimens with oxaliplatin and/or irinotecan and a biologic agent. Immunotherapy may enhance antitumor activity in combination with standard therapies in patients with mCRC. Here, we present phase 2 results of nivolumab plus standard-of-care therapy (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab) versus SOC in the first-line treatment of patients with mCRC (CheckMate 9X8).Methods CheckMate 9X8 was a multicenter, open-label, randomized, phase 2/3 trial. Eligible patients were at least 18 years of age with unresectable mCRC and no prior chemotherapy for metastatic disease. Patients were randomized 2:1 to receive nivolumab 240 mg plus SOC or SOC alone every 2 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included PFS by investigator assessment; objective response rate (ORR), disease control rate, duration of response, and time to response, all by BICR and investigator assessments; overall survival; and safety. Preplanned exploratory biomarker analyses were also performed.Results From February 2018 through April 2019, 310 patients were enrolled, of which 195 patients were randomized to nivolumab plus SOC (n=127) or SOC (n=68). At 21.5-month minimum follow-up, PFS with nivolumab plus SOC versus SOC did not meet the prespecified threshold for statistical significance; median PFS by BICR was 11.9 months in both arms (HR, 0.81 (95% CI, 0.53 to 1.23); p=0.30). Higher PFS rates after 12 months (18 months: 28% vs 9%), higher ORR (60% vs 46%), and durable responses (median 12.9 vs 9.3 months) were observed with nivolumab plus SOC versus SOC. Grade 3–4 treatment-related adverse events were reported in 75% versus 48% of patients; no new safety signals were identified.Conclusions The CheckMate 9X8 trial investigating first-line nivolumab plus SOC versus SOC in patients with mCRC did not meet its primary endpoint of PFS by BICR. Nivolumab plus SOC showed numerically higher PFS rates after 12 months, a higher response rate, and more durable responses compared with SOC alone, with acceptable safety. Further investigation to identify subgroups of patients with mCRC that may benefit from nivolumab plus SOC versus SOC in the first-line setting is warranted.Trial registration number NCT03414983.

Abstract Unsaturated fatty acids have been reported to be associated with the risk of psoriasis. However, the causal relationship between them remains unclear This study aimed to explore the causal relationship between unsaturated FAs and psoriasis. Firstly, we obtained genome‐wide association study (GWAS) data for psoriasis from the FINNGEN database (number of cases = 4510, number of controls = 212,242) and different FA levels (number of samples = 114,999) from the IEU OpenGWAS Project. Secondly, the genetic correlation coefficient was calculated using linkage disequilibrium fractional regression. Thirdly, a two‐sample Mendelian randomization (MR) analysis was performed using independent instrumental variables (p

AbstractObjective Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells.Methods An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays.Results NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation.Conclusion The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.

The decomposition integrals of set-valued functions with regards to fuzzy measures are introduced in a natural way. These integrals are an extension of the decomposition integral for real-valued functions and include several types of set-valued integrals, such as the Aumann integral based on the classical Lebesgue integral, the set-valued Choquet, pan-, concave and Shilkret integrals of set-valued functions with regard to capacity, etc. Some basic properties are presented and the monotonicity of the integrals in the sense of different types of the preorder relations are shown. By means of the monotonicity, the Chebyshev inequalities of decomposition integrals for set-valued functions are established. As a special case, we show the linearity of concave integrals of set-valued functions in terms of the equivalence relation based on a kind of preorder. The coincidences among the set-valued Choquet, the set-valued pan-integral and the set-valued concave integral are presented.

Lung cancer is the most common cause of cancer-related deaths worldwide. More efficient treatments are desperately needed. For decades, the success of platinum-based anticancer drugs has promoted the exploration of metal-based agents. Four ruthenium-based complexes have also entered clinical trials as candidates of anticancer metallodrugs. However, systemic toxicity, severe side effects and drug-resistance impeded their applications and efficacy. Stimuli-responsiveness of Pt- and Ru-based complexes provide a great chance to weaken the side effects and strengthen the clinical efficacy in drug design. This review provides an overview on the stimuli-responsive Pt- and Ru-based metallic anticancer drugs for lung cancer. They are categorized as endo-stimuli-responsive, exo-stimuli-responsive, and dual-stimuli-responsive prodrugs based on the nature of stimuli. We describe various representative examples of structure, response mechanism, and potential medical applications in lung cancer. In the end, we discuss the future opportunities and challenges in this field.

Resistance to cisplatin (DDP) is a major obstacle in the clinical treatment of advanced gastric cancer (GC). Long noncoding RNA (lncRNA) play a significant regulatory role in the development and drug resistance of GC. In this study, we reported that the lncRNA LINC-PINT was downregulated in DDP-resistant GC cells. Functional studies showed that LINC-PINT inhibited proliferation and migration of DDP-resistant GC cells in vitro, and overexpression of LINC-PINT could enhance the sensitivity of DDP-resistant GC cells to DDP. Further investigation revealed that LINC-PINT recruited enhancer of zeste homolog 2 (EZH2) to the promotor of ATG5 to inhibit its transcription, leading to the suppression of autophagy and DDP resensitization. Collectively, our results revealed how the LINC-PINT/EZH2/ATG5 axis regulates autophagy and DDP resistance in GC. These data suggest that LINC-PINT may be a potential therapeutic target in GC.

We aimed to examine the effect of natto and red yeast rice (NR) supplementation on lipid and lipoprotein profiles, gene expressions of cholesterol metabolism, and the composition of gut microbiota in ApoE-/- mice. Forty-one male ApoE-/- mice aged 7–8 wks old were randomly fed a control diet (CD), CD + NR (oral gavage at 0.3 g/kg BW/day), high-fat and high-cholesterol diet (HFD), or HFD + NR for 12 wks. Fasting blood samples, liver and intestine tissues and fecal samples were collected at week 12. Biochemical parameters, gene expressions in cholesterol metabolism and gut microbiota composition and diversity were measured using standard methods. NR supplementation had no significant effect on lipid and lipoprotein profiles. Compared with the HFD group, HFD + NR resulted in higher mRNA expressions of HMGCR and CYP7A1 (both P-NR < 0.05) and ABCA1 (P-diet*NR = 0.0134, P-NR = 0.0407), lower mRNA expression of PCSK9 (P-diet*NR = 0.0002), lower fasting glucose concentrations (P-diet*NR = 0.0011), and lower relative abundance of genera Bacteroides and Lactococcus (both P-NR < 0.01) and Coriobacteriaceae_UCG-002 (P-diet*NR = 0.0007). The relative abundance of Lactococcus was inversely correlated with HMGCR and CYP7A1, and the relative abundance of Coriobacteriaceae_UCG-002 was positively correlated with PCSK9 and inversely correlated with ABCA1 (all P < 0.05). These findings suggest that NR supplementation may regulate gene expressions in cholesterol metabolism via changes in the gut microbiota in HFD-fed ApoE-/- mice.

Dietary glycemic index (GI), carbohydrate to fiber ratio (CF) and carbohydrate quality index (CQI) are conventional and emerging indicators for carbohydrate quality. We aimed to investigate the associations between these indicators and new-onset type 2 diabetes mellitus (T2DM) risk among Chinese adults. This prospective cohort study included 14,590 adults from the China Health and Nutrition Survey without cardiometabolic diseases at baseline. The associations between dietary GI, CF and CQI and T2DM risk were assessed using Cox proportional hazard regression analysis and dose–response relationships were explored using restricted cubic spline and threshold analysis. After a mean follow-up duration of 10 years, a total of 1053 new-onset T2DM cases occurred. There were U-shaped associations between dietary GI and CF and T2DM risk (both P-nonlinear < 0.0001), and T2DM risk was lowest when dietary GI was 72.85 (71.40, 74.05) and CF was 20.55 (17.92, 21.91), respectively (both P-log likelihood ratio < 0.0001). Inverse associations between CQI and T2DM risk specifically existed in participants < 60 y or attended middle school or above (both P-trend < 0.05). These findings indicated that moderate dietary GI and CF range and a higher dietary CQI score may be suggested for T2DM prevention in Chinese adults.

Psoriasis is a chronic inflammatory skin disease, and elevation of proinflammatory cytokine levels is a critical driver of the pathogenesis of psoriasis. Extracellular cold-inducible RNA-binding protein (eCIRP) has been shown to play a role in various acute and chronic inflammatory diseases. C23, a short peptide derived from CIRP, competitively binds CIRP receptors and reduces damage in inflammatory diseases. However, the effect of eCIRP in psoriasis has not been studied. In the present study, we investigated the role of eCIRP in the expression of proinflammatory cytokines in keratinocytes. Our data show that eCIRP expression was increased in the sera of psoriasis patients and imiquimod- (IMQ-) induced psoriatic mice and cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). Recombinant human CIRP (rhCIRP) promoted the expression of the proinflammatory cytokines TNF-α, IL-6, and IL-8 and the activation of NF-kappaB (NF-κB) and ERK1/2 in cultured keratinocytes. We then found that the above effects of eCIRP could be blocked by C23 in both normal keratinocytes and M5-stimulated psoriatic keratinocytes. In addition, in vivo experiments revealed that C23 could effectively ameliorate IMQ-induced psoriatic dermatitis. TNF-α and IL-6 mRNA expressions were reduced in the skin lesions of mice with C23-treated IMQ-induced psoriasis, and this effect was accompanied by inhibition of the NF-κB and ERK1/2 signaling pathways. In summary, eCIRP plays an important role in the pathogenesis of psoriasis and may become a new target for psoriasis treatment.

Abstract The rapid development of microelectronics has equally rapidly increased the demand for miniaturized energy storage devices. On‐chip microsupercapacitors (MSCs), as promising power candidates, possess great potential to complement or replace electrolytic capacitors and microbatteries in various applications. However, the areal capacities and energy densities of the planar MSCs are commonly limited by the low voltage window, the thin layer of the electrode materials and complex fabrication processes. Here, a new‐type three‐dimensional (3D) tubular asymmetric MSC with small footprint area, high potential window, ultrahigh areal energy density, and long‐term cycling stability is fabricated with shapeable materials and photolithographic technologies, which are compatible with modern microelectronic fabrication procedures widely used in industry. Benefiting from the novel architecture, the 3D asymmetric MSC displays an ultrahigh areal capacitance of 88.6 mF cm−2 and areal energy density of 28.69 mW h cm−2, superior to most reported interdigitated MSCs. Furthermore, the 3D tubular MSCs demonstrate remarkable cycling stability and the capacitance retention is up to 91.8% over 12 000 cycles. It is believed that the efficient fabrication methodology can be used to construct various integratable microscale tubular energy storage devices with small footprint area and high performance for miniaturized electronics.

Available data investigating the associations between dietary animal and plant protein intakes and cardiometabolic risk factors (CMRFs) among populations with habitual plant-based diets are heterogenous and limited in scope. The current study was to assess the associations between dietary animal and plant protein intakes and CMRFs, including lipid and lipoprotein profiles, glucose homeostasis biomarkers, low-grade chronic inflammatory biomarker and uric acid in Chinese adults. Data of 7886 apparently healthy adults were extracted from the China Health and Nutrition Survey 2009. Dietary protein (total, animal and plant) intakes were assessed with three consecutive 24 h dietary recalls, and CMRFs were measured with standard laboratory methods. Substituting 5% of energy intake from animal protein for carbohydrates was positively associated with total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and uric acid (all p < 0.05). Substituting 5% of energy intake from plant protein for carbohydrates was inversely associated with non-HDL-C and LDL-C:HDL-C ratio, and positively associated with HDL-C and glycated hemoglobin (all p < 0.05). Some of these associations varied in subgroup analyses by BMI, sex, age or region. There were no significant associations between animal or plant protein intakes and high-sensitivity C-reactive protein. The public health implication of these findings requires further investigation.

Studies investigating the associations between dietary glycemic index (GI) and glycemic load (GL) values and cardiometabolic risk factors (CMRF) among Chinese populations are strikingly limited. To assess the associations between dietary GI and GL values and CMRF, including dyslipidemia, hyperglycemia, and hyperuricemia in Chinese adults, we extracted data of 7886 apparently healthy adults from the 2009 wave of the China Health and Nutrition Survey. Dietary GI and GL values were calculated using data collected from three consecutive 24 h dietary recalls. Fasting lipid, glucose, and uric acid concentrations were measured and CMRF were defined on the basis of established criteria. There were no significant associations between dietary GI values and CMRF, and analyzing the data by age, sex, body mass index (BMI), and region did not alter these results. Dietary GL values were positively associated with prevalence of hyperuricemia in all participants (Q4 compared with Q1: odds ratio (OR) = 1.46; 95% CI: 1.14, 1.87; p-trend = 0.0030) and prevalence of hypercholesterolemia in participants ≥ 60 years old (Q5 compared with Q1: OR = 1.72; 95% CI: 1.11, 2.68; p-trend < 0.0010). Higher dietary GL but not GI values were associated with increased prevalence of hyperuricemia in apparently healthy Chinese adults and hypercholesterolemia in older Chinese adults. Further studies are required to confirm the public health implication of these findings.

Parameter estimation of photovoltaic (PV) models from experimental current versus voltage (I-V) characteristic curves acts a pivotal part in the modeling a PV system and optimizing its performance. Although many methods have been proposed for solving this PV model parameter estimation problem, it is still challenging to determine highly accurate and reliable solutions. In this paper, this problem is firstly transformed into an optimization problem, and an objective function (OF) is formulated to quantify the overall difference between the experimental and simulated current data. And then, to enhance the performance of original cuckoo search algorithm (CSA), a novel improved cuckoo search algorithm (ImCSA) is proposed, by combining three strategies with CSA. In ImCSA, a quasi-opposition based learning (QOBL) scheme is employed in the population initialization step of CSA. Moreover, a dynamic adaptation strategy is developed and introduced for the step size without Lévy flight step in original CSA. A dynamic adjustment mechanism for the fraction probability (Pa) is proposed to achieve better tradeoff between the exploration and exploitation to increase searching ability. Afterwards, the proposed ImCSA is used for solving the problem of estimating parameters of PV models based on experimental I-V data. Finally, the proposed ImCSA has been demonstrated on the parameter identification of various PV models, i.e., single diode model (SDM), double diode model (DDM) and PV module model (PMM). Experimental results indicate that the proposed ImCSA outperforms the original CSA and its superior performance in comparison with other state-of-the-art algorithms, and they also show that our proposed ImCSA is capable of finding the best values of parameters for the PV models in such effective way for giving the best possible approximation to the experimental I-V data of real PV cells and modules. Therefore, the proposed ImCSA can be considered as a promising alternative to accurately and reliably estimate parameters of PV models.

Increasing demand for electricity has placed heavy stress on power system security. Therefore, this paper focuses on the problem of how to maximize power system static security in terms of branch loading and voltage level under normal operation and even the most critical single line contingency conditions. This paper proposes a hybrid approach to find out the optimal locations and settings of two classical types of flexible AC transmission system (FACTS) devices, namely thyristor-controlled series compensators (TCSCs) and static var compensators (SVCs) for solving this problem. Our proposed approach requires a two-step strategy. Firstly, the min cut algorithm (MCA) and tangent vector technique (TVT) are applied to determine the proper candidate locations of TCSC and SVC respectively so as to reduce the search scope for a solution to the problem, and then the cuckoo search algorithm (CSA) is employed to solve this problem by simultaneously optimizing the locations and settings for TCSC and SVC installation. The proposed hybrid approach has been verified on the IEEE 6-bus and modified IEEE 14-bus test systems. The results indicate that CSA outperforms particle swarm optimization (PSO), proving its effectiveness and potential, and they also show that our proposed hybrid approach can find the best locations and settings for TCSC and SVC devices as an effective way for enhancing power system static security by removing or alleviating the overloads and voltage violations under normal operation and even the most critical single line contingency conditions. Using this hybrid approach, the search space for solution to the problem becomes limited hence the computational burden will be decreased.

Defect detection in complex background is a critical issue. To address this issue, this paper proposes the mixture attention mechanism cascade network, in which the new channel attention network is linked with the spatial attention network to create an effective mixed attention network that takes advantage of their respective advantages, adaptively suppresses background noise, and highlights defect features. To ensure the efficiency and effectiveness of effective mixed attention network, the new channel attention network splices the output features of the global average pooling layer and the global maximum pooling layer and then sends the spliced features into a shared network, which is a one‐dimensional convolutional network, and uses cross‐channel interaction for fusion. Furthermore, in order to provide more discriminative feature representation, the authors extract the intermediate features of the region proposal network and input them into effective mixed attention network. Finally, the cascade head is used to refine the predicted bounding box to achieve high‐quality defect location. To demonstrate the superiority and usefulness of this method, it is compared to the latest method using widely used PCB and NEU data sets. A large number of trials demonstrate that this strategy outperforms other methods for detecting defects in complicated backgrounds. [ABSTRACT FROM AUTHOR]

In the electricity market, power producers and customers share a common transmission network for wheeling power from generation to consumption points. All parties in this open access environment may try to produce energy from cheaper sources for greater profit margin, which may lead to transmission congestion, which could lead to violation of voltage and thermal limits, threatening the system security. To solve this, available transfer capability (ATC) must be accurately estimated and optimally utilized. Thus, accurate determination of ATC to ensure system security while serving power transactions is an open and trending research topic. Many optimization approaches to deal with the problem have been proposed. In this paper, Cuckoo Search Algorithm (CSA) is applied for determining ATC problem between the buses in deregulated power systems without violating system constraints such as thermal, voltage constraints. The suggested methodology is tested on IEEE 14 and IEEE 24- bus for normal and contingency cases. The simulation results are compared with the corresponding results of EP, PSO, and GWO and show that the CSA is an effective method for determining ATC. [ABSTRACT FROM AUTHOR]