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ObjectiveCognitive-behavioral stress management (CBSM) is a psychotherapy that helps patients cognize and manage stress to improve mental health and quality of life. This study aimed to explore the influence of CBSM on anxiety, depression, and quality of life in non-small cell lung cancer (NSCLC) patients.MethodsIn total, 172 NSCLC patients who received tumor resection were randomized 1:1 into the usual care (UC) group (N = 86) and CBSM group (N = 86) to receive 10-week UC and CBSM interventions. Moreover, all participants attended a 6-month follow-up.ResultsHospital Anxiety and Depression Scales (HADS)-anxiety score at 3rd month (M3) (P = 0.015) and 6th month (M6) (P = 0.018), HADS-depression score at M3 (P = 0.040) and M6 (P = 0.028), and depression rate at M6 (P = 0.035) were descended in CBSM group compared to UC group. Besides, depression severity was reduced at M6 (P = 0.041) in CBSM group compared to UC group, but anxiety severity only showed a decreased trend (P = 0.051). Additionally, Quality of Life Questionnaire-Core 30 (QLQ-C30) global health status score and QLQ-C30 function score at 1st month (M1), M3, and M6 were elevated (all P < 0.05), while QLQ-C30 symptoms score was declined at M1 (P = 0.031) and M3 (P = 0.014) in CBSM group compared to UC group. Notably, the efficacy of CBSM was impressive in patients with baseline depression or undergoing adjuvant therapy.ConclusionCBSM is a feasible intervention that effectively improves mental health and quality of life in postoperative NSCLC patients.

The visual N1 (N170) component with occipito-temporal negativity and fronto-central positivity is sensitive to visual expertise for print. Slightly later, an N200 component with an increase after stimulus repetition was reported to be specific for Chinese, but found at centro-parietal electrodes against a mastoid reference. Given the unusual location, temporal proximity to the N1, and atypical repetition behavior, we aimed at clarifying the relation between the two components. We collected 128-channel EEG data from 18 native Chinese readers during a script decision experiment. Familiar Chinese one-and two-character words were presented among unfamiliar Korean control stimuli with half of the stimuli immediately repeated. Stimulus repetition led to a focal increase in the N1 onset and to a widespread decrease in the N1 offset, especially for familiar Chinese and also prominently near the mastoids. A TANOVA analysis corroborated robust repetition effects in the N1 offset across ERP maps with a modulation by script familiarity around 300 ms. Microstate analyses revealed a shorter N1 microstate duration after repetitions, especially for Chinese. The results demonstrate that the previously reported centro-parietal N200 effects after repetitions reflect changes during the N1 offset at occipito-temporal electrodes including the mastoids. Although larger for Chinese, repetition effects could also be found for two-character Korean words, suggesting that they are not specific for Chinese. While the decrease of the N1 offset after repetition is in agreement with a repetition suppression effect, the microstate findings suggest that at least part of the facilitation is due to accelerated processing after repetition.

Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China.A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans.Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p0·0001) for participants in the screened group compared with those in the non-screened group.One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies.Ministry of Finance and National Health Commission of the People's Republic of China.For the Chinese translation of the abstract see Supplementary Materials section.

Mitochondrial function is closely related to the body's oxidative stress level and lifespan.

IntroductionSargassum fusiform is considered a traditional Chinese medicinal herb to treat many diseases, Sargassum fusiform polysaccharides (SFPS) were found to display many important biological activities. The purpose of this study was to investigate the in vitro antioxidant activity of crude polysaccharide from Sargassum fusiforme and its protective effect against H2O2-induced injury in LO2 cells.MethodsSFPS was extracted from Sargassum fusiforme using water extraction and alcohol precipitation. High-performance liquid chromatography (HPLC) was used to measure its monosaccharide composition. The in vitro antioxidant activity of SFPS was evaluated using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays. Moreover, its hepatoprotective activity was examined by establishing H2O2-induced LO2 cells injury model.Results and discussionThe results showed that the SFPS was composed of Glc, Ara, Fuc, Gal, Man, Rha and Xyl. Meanwhile, SFPS exhibited strong antioxidant activity and potential hepatoprotective effect. Further studies found that SFPS could alleviate LO2 cells injury induced by H2O2 via decreasing malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, increasing superoxide dismutase (SOD) and catalase (CAT) activities and inhibiting intracellular reactive oxygen species (ROS) production. These results revealed that SFPS had the ability to protect the liver cells from H2O2-induced liver injury through its antioxidant activity.

The antiaging effects of sea red rice bran

The dysfunction of memory CD8

Heparinoid, a type of compound that has structures similar to heparin, has been found in marine organisms such as shrimp head. This shrimp waste products were used to prepare, characterize, and evaluate the antithrombotic effect of heparinoid. Two heparinoid compounds were obtained from shrimp head, and the main fraction F1 was →4)-GlcA-(1→3)-GalNAc-(1→ with Ara, while the minor fraction F2 composed mainly of the backbone as →4)-β-D-GlcA (or IdoA)-(1→4)-β-D-GlcN (or GlcNAc)-(1→. Both F1 and F2 could extend activated partial thromboplastin time and thrombin time concentration-dependently, and F2 has stronger activity than F1 at the same concentration. The potential anticoagulant mechanism of F1 and F2 may relate to their combination with more antithrombin III, which binds to and potentiates the action of antithrombin as well as inhibiting coagulation factors Xa and IIa, preventing blood clot formation. Furthermore, heparinoid F1 and F2 were found to have high fibrinolytic capability in vitro and in vivo via activating the self-fibrinolytic system. In conclusion, heparinoids (F1 and F2) derived from shrimp head wastes could be used as candidate compounds to prevent thrombosis while posing a lower hemorrhagic risk.

Mitochondrial function is closely related to the body's oxidative stress level and lifespan. Our previous research demonstrated that the combination of blueberry extracts (BE) and apple peel extracts (APE) could synergistically promote the oxidative stress and lifespan of

Background: The Hong Kong Brief Cognitive Test (HKBC), a brief instrument designed to screen for cognitive impairment in older adults, has been validated in Cantonese-speaking populations and has shown better performance than the Mini-Mental State Examination (MMSE) in detecting both mild and major neurocognitive disorder (NCD). Objective: This study aimed to validate the HKBC for detecting patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) in a Mandarin-speaking Chinese population. Methods: Two hundred forty-eight patients with aMCI, 67 patients with mild AD and 306 healthy controls (HCs) were recruited for this study and completed both the HKBC and the MMSE. The performance of the HKBC and MMSE in distinguishing patients with aMCI from HCs and distinguishing patients with AD from patients with aMCI was compared in the whole population and in age- and education-stratified subgroups. Results: The optimal HKBC cutoff score for distinguishing patients with aMCI from HCs was 23, and the optimal cutoff score for distinguishing patients with AD from patients with aMCI was 17. The HKBC significantly outperformed the MMSE at differentiating patients with aMCI from HCs in the whole population (z = 12.38, p

Background The dysfunction of memory CD8+T cell can not be reverted by successful clearance of hepatitis C virus (HCV) after direct-acting antivirals (DAA) therapy, increasing the risk of reinfection with HCV. Stem cell-like memory T cells (Tscm) with superior capacities of long-lasting, self-renewing, and multipotency that contribute to the maintenance of immune function. Methods We investigated the impact of HCV infection on CD8+Tscm, and the possible role this compartment may has in disease progression, by using DAA-naïve HCV monoinfected and HIV/HCV coinfected cohorts. The distribution of memory CD8+T cell subsets and the level of T cell immune activation were determined by flow cytometry. Associations between CD8+Tscm and other memory T cell subsets, HCV viral load, as well as the level of T cell immune activation were analyzed. Results We observed that the proportion of CD8+Tscm increased in both HCV and HIV/HCV individuals. The proportion of CD8+Tscm had a positive correlation with that of CD8+Tcm, and a negative correlation with that of CD8+Tem, representing the contribution of CD8+Tscm in T cell homeostasis. In addition, higher frequency of CD8+Tscm indicated lower HCV viral load and less T cell immune activation in HCV monoinfection, which suggested that CD8+Tscm may associate with effective control of HCV replication. Conclusions CD8+Tscm may has protective immunity to HCV infection. Considering the characteristics of Tscm, our current study opens new opportunity for Tscm-based vaccine design and immunotherapy development to achieve HCV elimination.

Heparinoid, a sulfate polysaccharide derived from marine organisms was attracted largely attention due to its versatile activities. A naturally occurring heparinoid (M2) that was extracted from the mollusk

Fucoidan has many biological functions, including anti-tumor activity. Additionally, it has been suggested that low-molecular-weight fucoidans have greater bioactivities. This study aimed to examine the degradation, purification, physicochemical characterization and in vitro antitumor activity of fucoidan from Sargassum hemiphyllum (Turner) C. Agardh. Fucoidan was isolated using DEAE-cellulose-52 (F1, F2), Vc-H2O2 degration, and Sepharose CL-6B gel (DF1, DF2) from crude Sargassum fucoidans. Physicochemical characteristics of four isolated fucoidans were examined using chemical and monosaccharide composition, average molecular weight (Mw), and FTIR. Furthermore, the anti-proliferative effects of purified fucoidans on human hepatocellular carcinoma cells (HepG2), human Burkitt Lymphoma cells (MCF-7), human uterine carcinoma cells (Hela) and human lung cancer cells (A549) were analyzed by MTT method. The apoptosis of HepG2 cells was detected by flow cytometry. Our data suggest that the contents of polysaccharide, L-fucose and sulfate of DF2 were the highest, which were 73.93%, 23.02% and 29.88%, respectively. DF1 has the smallest molecular weight (14,893 Da) followed by DF2 (21,292 Da). The four fractions are mainly composed of fucose, mannose and rhamnose, and the infrared spectra are similar, all of which contain polysaccharide and sulfate characteristic absorption peaks. The results of MTT assay showed that the four fractions had inhibitory effects on HepG2 and A549 in the range of 0.5–8 mg/mL, and the four fractions had strong cytotoxic effects on HepG2 cells. DF2 had the best inhibitory effect on HepG2 (IC50 = 2.2 mg/mL). In general, the antitumor activity of Sargassum fucoidans is related to the content of L-fucose, sulfate and molecular weight, and Sargassum fucoidan has the best inhibitory effect on HepG2 hepatocellular carcinoma cells. Furthermore, when compared to MCF-7, Hela, and A549 cells, Sargassum fucoidans had the best capacity to reduce the viability of human hepatocellular carcinoma cells (HepG2) and to induce cell apoptosis, proving itself to have a good potential in anti-liver cancer therapy.

With the gradual realization of China’s 14th Five-Year Plan, the proportion of installed renewable energy capacity in all regions has increased significantly. The access of a high proportion of renewable energy has brought serious challenges to the safe and stable operation of the power system. The uncertainty of wind power and photovoltaic output makes it difficult for the traditional reserve demand determination method to economically and effectively calculate the reserve capacity required by the system, so it is urgent to propose a reasonable reserve capacity demand determination method. On the one hand, it ensures that the deserve capacity needed by the system is sufficient to cope with real-time active fluctuations, and on the other hand, it improves the economy of the reserve capacity. The reserve demand determination method considering the different time periods uncertainty of wind and solar in this paper is able to meet the reserve demand of new power system. At last, the article proves the benefits of Reserve Demand Determination Method through a numerical example.

Increased consumption of fruit and vegetables is associated with a reduced risk of age-related functional decline and chronic diseases, which is primarily attributed to their phytochemicals. Apples and blueberries are rich in phytochemicals with a wide range of biological activities and health benefits. The objective of this study was to determine whether the combination of apple peel extracts (APE) and blueberry extracts (BE) had synergistic effects in promoting lifespan in Caenorhabditis elegans (C. elegans), and to explore the underlying mechanisms of action. The results showed that the lifespan of C. elegans treated with APE plus BE was increased by 31.4%, which is significantly more than with APE or BE alone, and extended the health span of animals, including improving motility and enhancing resistance to heat stress and UV-B radiation in C. elegans. Meanwhile, treatment with APE plus BE could regulate the expression of anti-aging related genes, and promote the migration of DAF-16 into the nucleus. In addition, administration with APE plus BE eradicated the extension of the lifespan of mutants, and inhibited the expression of the daf-16 downstream gene. In conclusion, the combination of APE and BE could synergistically promote the lifespan via the insulin signaling pathway and DAF-16 in C. elegans.

Increased consumption of fruits and vegetables is associated with a reduced risk of age-related functional decline and chronic diseases, which is primarily attributed to phytochemicals. Raspberries are rich in phytochemicals with a wide range of biological activities and health benefits. However, little is known about their effects on aging. The objective of this study was to determine whether raspberry extract (RE) could promote lifespan and stress resistance in Caenorhabditis elegans (C. elegans), and to explore the underlying mechanisms of action. The results showed that the mean lifespan of C. elegans treated with RE at 20, 40 and 80 mg mL-1 was significantly increased by 13.6%, 22.9% and 29.7%, respectively, in a dose-dependent manner. Supplementation with RE decreased the accumulation of lipofuscin and extended the healthspan of animals by improving motility and enhancing resistance to heat stress and UV-B radiation in C. elegans. Meanwhile, treatment with RE could regulate the expression of anti-aging related genes, including daf-2, age-1, akt-2, sir-2.1, daf-16, skn-1, jnk-1 and hsp-16.2, and promote the migration of DAF-16 into the nucleus. In addition, administration with RE abolished the extension of the lifespan of daf-2(e1370) mutants and RNAi (daf-16) C. elegans, and inhibited the expression of daf-16 downstream genes, including sod-3, ctl-2, dod17 and clk-1. In conclusion, RE could prolong the lifespan, improve the healthspan and enhance stress resistance in C. elegans by the insulin/IGF signaling pathway and DAF-16, providing a theoretical basis to fully exploit raspberry in the prevention of aging and healthcare.

Increased consumption of fruits and vegetables is associated with reduced risk of age-related functional declines and chronic diseases, primarily attributed to their bioactive phytochemicals. Apples and blueberries are rich in phytochemicals with a wide range of biological activities and health benefits. Our previous research has shown the combination of apple peel extracts (APE) and blueberry extracts (BE) can synergistically promote the lifespan of Caenorhabditis elegans (C. elegans). The objectives of this study were to determine whether the extension of lifespan was involved in regulation of oxidative stress, and to explore the underlying mechanisms of action. The results showed that the combination of APE and BE could synergistically ameliorate oxidative stress by improving antioxidant enzyme activities and enhancing resistance to paraquat. Meanwhile, treatment with APE plus BE could down-regulate the overexpression of reactive oxygen species (ROS) and affect the expression of antioxidant related genes, including sod-3, cat-1, ctl-1, skn-1, mev-1 and isp-1. However, administration with APE plus BE abolished the extension of the lifespan of skn-1(zu135) mutants, and inhibited the expression of skn-1 downstream genes, including gcs-1, gst-4 and gst-7. In addition, supplementation with APE plus BE could promote the migration of SKN-1 into the nucleus, which eliminated improvement to ROS and paraquat. In conclusion, the combination of APE and BE could synergistically protect against oxidative stress in C. elegans via the SKN-1/Nrf2 pathway. This study provided the theoretical basis to explore the combination of phytochemicals in the prevention of aging regulated by oxidative stress.

Purpose: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer. Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. Results: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. Conclusions: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Hydrochloric droplets and sulfuric droplets are two common contaminants in indoor environments. The different mechanisms of phase change may cause different transport behaviours in them. This paper presents fundamental research conducted to numerically investigate the free fall of single hydrochloric droplets and sulfuric droplets. The influence of the initial diameter and relative humidity (RH) are considered. The diameter change and falling distance of these two types of droplets were compared and discussed. The results show that the phase change and motion of the two types of droplets are quite different. It was possible for the hydrochloric droplets to evaporate completely, while it was not for the sulfuric droplets. The sulfuric droplets have a minimum size and show a linear tendency of increase in size with the increase in initial diameter at a certain RH. The evaporation time of a hydrochloric droplet exhibits an exponential relationship with the initial diameter at a certain RH. A two-stage motion behaviour is observed on comparing the falling distances between the two types of droplets under identical initial conditions. The falling distances of the hydrochloric droplets at different initial sizes and RH were determined. Furthermore, it was found that the falling of single hydrochloric and sulfuric droplets could be severely mispredicted if the solution effect and/or HCl volatilisation is ignored. The results of this study could contribute to the accurate prediction and evaluation of the damage inflicted by hydrochloric and sulfuric droplets on human health, equipment, and building structures.

The efficient removal of droplets with different ventilation systems is a key scientific problem affecting an indoor environment. In this study the transport of monodispersed droplets generated from an open tank with a large length/width ratio was investigated under the influence of an upper-receiving ventilation (URV) system and a push-pull ventilation (PPV) system, based on numerical simulation. The movement of droplets under the two systems were compared. The effects of the initial diameters of the droplets and the exhaust airflow velocity on the capture efficiency and removal rate of droplets were evaluated. The results showed that the turbulence dispersion of droplets, gravity acting on the droplets and vortex interaction contributed to the different droplet behaviour under different local ventilation modes and exhaust airflow velocities. The PPV system demonstrated faster droplet removal ability than the URV system, for the same size of droplets. The URV system achieved higher capture efficiency with less energy consumption than the PPV system for droplets with an initial diameter of 10–50 μm; for those with an initial diameter of 75–100 μm, the PPV system prevented any droplets from escaping into the occupied zone with less energy cost. The results of this study can contribute to the design and selection of local ventilation modes and the operation conditions required to control droplets.

Adversarial examples easily mislead vision systems based on deep neural networks (DNNs) trained with softmax cross entropy (SCE) loss. The vulnerability of DNN comes from the fact that SCE drives DNNs to fit on the training examples, whereas the resultant feature distributions between the training and adversarial examples are unfortunately misaligned. Several state-of-the-art methods start from improving the inter-class separability of training examples by modifying loss functions, where we argue that the adversarial examples are ignored, thus resulting in a limited robustness to adversarial attacks. In this paper, we exploited the inference region, which inspired us to apply margin-like inference information to SCE, resulting in a novel inference-softmax cross entropy (I-SCE) loss, which is intuitively appealing and interpretable. The inference information guarantees that it is difficult for neural networks to cross the decision boundary under an adversarial attack, and guarantees both the inter-class separability and the improved generalization to adversarial examples, which was further demonstrated and proved under the min-max framework. Extensive experiments show that the DNN models trained with the proposed I-SCE loss achieve a superior performance and robustness over the state-of-the-arts under different prevalent adversarial attacks; for example, the accuracy of I-SCE is 63% higher than SCE under the PGD50un attack on the MNIST dataset. These experiments also show that the inference region can effectively solve the misaligned distribution.

The gut microbiota dysbiosis is a state which the physiological combinations of flora are transformed into pathological combinations caused by factors such as diets, pollution, and drugs. Increasing evidence shows that dysbiosis is closely related to many diseases. With the continuous development and utilization of marine resources, marine polysaccharides have been found to regulate dysbiosis in many studies. In this review, we introduce the types of dysbiosis and the degree of it caused by different factors. We highlight the regulating effects of marine polysaccharides on dysbiosis as a potential prebiotic. The mechanisms of marine polysaccharides to regulate dysbiosis including protection of intestinal barrier, regulatory effect on gut microbiota, alteration for related metabolites, and some other possible mechanisms were summarized. And we aim to provide some references for the high-value utilization of marine polysaccharides and new targets for the treatment of gut microbiota dysbiosis by this review.

Low molecular weight sulfate glycosaminoglycan has attracted more attention recently for its great bioactivity. In the present study, a degraded sulfate glycosaminoglycan (named D-SBSG) was prepared from swimming bladder by enzymatic depolymerization, the structure characteristics of D-SBSG and its effects on blood coagulation and inflammation in vitro was investigated. HPGPC analysis showed that the molecular weight (Mw) of SBSG was 115.84 kDa, while the Mw of D-SBSG was 4.96 kDa. The bioactivities had arose dramatic differences, though its main molecule structure had little change after enzymatic degradation. Compared with heparin sodium, relatively milder anticoagulant activity in vitro, which were positively associated with molecular weight, were found in SBSG and D-SBSG. In contrast, the results of anti-inflammatory assays indicated that D-SBSG with the lower molecular weight possessed higher bioactivity than SBSG. Additionally, the D-SBSG inhibited the LPS-induced inflammatory in RAW264.7 macrophages by down-regulation of inflammatory mediators, both of NF-κB (including p65) and MAPK (including p38) signaling pathways to exert its anti-inflammatory function. These results indicated that enzymolysis is a viable strategy for degradation of sulfate glycosaminoglycan, and D-SBSG could be a promising ingredient for inflammation management.

e21528 Background: Avelumab is an anti–PD-L1 monoclonal antibody that was approved in Japan for the treatment of patients with curatively unresectable MCC in Sept 2017. Because the number of Japanese patients with MCC participating in the global Phase II JAVELIN Merkel 200 study was limited (3 patients), Japan was mandated to conduct an all-case surveillance as a post-marketing surveillance (PMS) study. In the all-case surveillance, safety and efficacy information is accumulated with respect to a defined period of time or a defined number of post-approval prescription cases and is provided as real-world data. This report summarizes the results of the final analysis of this MCC PMS. Methods: This PMS is a multicenter, non-comparative, prospective, observational study. Since Nov 2017 (following approval in Japan), all patients with MCC who received at least one dose of avelumab in Japan were enrolled, and case report forms (CRF) were collected for all patients who started treatment through Oct 2019. Results: As of Sept 22, 2021, 152 patients from 86 sites were enrolled, and CRFs were collected from 77 patients. Of the 75 patients (53 sites) who met the analysis adequacy criteria, 48% were female, and the median age at the start of avelumab treatment was 77.0 years (42-95 years). Of the treatment lines in which avelumab was administered, 93.3% (70/75) were prescribed as first-line therapy. The incidence of adverse reactions was 61.3% (46/75), and 9.3% (7/75) discontinued treatment due to adverse reactions. Grade 3 and 4 adverse reactions occurred in 12.0% (9/75) and 4.0% (3/75), respectively; no grade 5 adverse reactions were reported. Infusion reactions were reported in 28.0% (21/75). The objective response rate (proportion of patients whose best response was assessed by the investigator as a complete or partial response) up to 1 year after the start of avelumab treatment was 45.3% (95% CI: 33.8, 57.3). The 1-year overall survival rate was 59.6% (95% CI: 47.0, 70.1). Conclusions: This study report is the first real-world evidence collected and analyzed from actual clinical use of avelumab in patients with curatively unresectable MCC in the East Asia region. Despite the different baseline patient characteristics, avelumab therapy in clinical practice had a manageable safety profile with no new safety concerns and has shown similar efficacy to that observed in the JAVELIN Merkel 200 trial.

Some syphilis patients do not exhibit an appropriate serological response after treatment despite the absence of any clinical evidence of treatment failure or reinfection. This condition is called “serofast syphilis” or “serological non-response syphilis.” This study explored the incidence of asymptomatic neurosyphilis (ANS) and related factors in 324 asymptomatic patients with serological non-response syphilis. We analyzed descriptive statistics stratified by the presence of asymptomatic neurosyphilis for the basic characteristics of samples. Bivariate analysis was conducted to assess correlations between outcomes and potential predictors. Variables significant in the bivariate analysis (p1:32. Our findings suggest that ANS is common among syphilis patients, and patients with a fourfold decrease in serum RPR titers after treatment and current serum RPR titers >1:32 are more likely to develop ANS.

Traffic data is the data foundation for smart transportation construction. However, due to inclement weather and equipment damage, there are often data missing during the collection of traffic data, which severely restricts smart transportation construction progress. Therefore, traffic data recovery has become an urgent problem in the field of intelligent transportation. Aiming at the problem that the recovery accuracy of existing traffic data recovery methods declines sharply under extreme missing conditions, this paper proposes a traffic data recovery model based on tensor filling and tensor matrix association analysis. The experimental results combined with real taxi GPS positioning data and point of interesting (POI) data of Kunming show that the traffic data recovery model proposed in this paper can significantly improve the recovery accuracy of missing data and maintain good stability in the case of extreme data missing.

It is challenging to predict droplet motion in numerical studies of particulate transport in indoor environment. This paper attempts at providing answers on this topic while using a Eulerian–Lagrangian method. The effect of the droplet release number and evaporation on prediction stability and accuracy was evaluated by modeling the droplet motion for two initial droplets (10 and 100 μm) and three different airflow patterns in an upper-receiving ventilation system. The results show that the effect of the droplet release number on prediction stability depends on the spatial scale of droplet motion, airflow pattern, and droplet number in a certain domain. Evaporation affected the motion and distribution of droplets, especially for those with an initial diameter of 100 μm. The number of droplets with an initial diameter of 100 μm escaping into the indoor environment was over predicted when ignoring droplet evaporation. The results may contribute to more accurate predictions of droplet transport by numerical simulation.

Map is a traditional visualization tool to represent distribution and interaction of spatial objects or spatial phenomenon. However, with the continuous development of acquisition and processing technologies for spatio-temporal data, traditional map can hardly meet the visualization requirement for this type of data. In other words, the dynamic information about spatial object or phenomenon cannot be expressed fully by traditional map. The Space-Time-Cube (STC), as a three-dimensional visualization environment, whose base represents the two-dimensional geographical space and whose height represents the temporal dimension, can simultaneously represent the spatial distribution as well as the temporal changes of spatio-temporal data. For some spatial object or phenomenon, its moving trajectory can be visualized in STC as a Space-Time-Path (STP), by which the speed and state of motion can be clearly reflected. Noticeably, the problem of visual clutter about STP is inevitably due to the complexity of three-dimensional visualization. In order to reduce the impact of visual clutter, this paper discusses different aspects about visualization representation of STP in the STC. The multiple scales representation and the multiple views display can promote interactive experience of users, and the application of different visual variables can help to represent different kinds of attribute information of STP. With the visualization of STP, spatio-temporal changes and attributive characters of spatial object or phenomenon can be represented and analysed.

Recently identified T memory stem (Tscm) cells have stem-cell-like properties, including long lifespan, self-renewal capacity, and multipotency to differentiate into other memory T cell types. In the study of simian immunodeficiency virus (SIV) infection, selective depletion of CCR5+CD4+ Tscm cells and the high proliferation rate of these cells are believed to be responsible for the pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study to investigate the influence of chronic human immunodeficiency virus (HIV)-1 infection on CD4+ Tscm cell homeostasis, and the effect of antiretroviral therapy (ART) on CD4+ Tscm cells. Chronic HIV-1 infection resulted in a decrease of the CD4+ Tscm cell proportion in HIV-1 patients. The decreased number of CD4+ Tscm cells in HIV-1 patients correlated positively with that of circulating CD4+ T cells. Further, the depletion of CD4+ Tscm cells was inversely correlated with an increased level of T cell immune activation during chronic HIV-1 infection. Prolonged ART recovered the CD4+ Tscm cells, and the dynamic change of CD4+ Tscm cells was in parallel with CD4+ T cell restoration and a decrease in the level of T cell immune activation. We propose that the abnormity of CD4+ Tscm cells may contribute to the pathogenesis and disease progression in HIV-1-infected individuals.

Insight into the effects of fertilization on soil organic carbon (C) content and composition, and on microbial community and functions related to C decomposition are being gained, although the linkage between them remains elusive. To address this knowledge gap, a field experiment was conducted under different fertilization regimes, no fertilization (CL), chemical fertilization for 11 years (CF), organic fertilization for 6 years (OF6) and organic fertilization for 11 years (OF11) in an alkaline sandy loam soil. Changes in soil C chemistry using 13C nuclear magnetic resonance (NMR) spectroscopy, microbial community using phospholipid fatty acid (PLFA) analysis and microbial functions using six hydrolase and three oxidoreductase enzyme activities were assessed. Fertilization significantly increased soil carbon contents, microbial biomass, and the abundance of fungi and bacteria. Nevertheless, CF induced a higher fungal-to-bacterial ratio due to a lower response in bacterial than fungal growth. In contrast, OF11 increased bacterial abundance, hydrolase activity, and consequently depleted labile C, resulting in higher alkyl-C contents and alkyl C/O-alkyl C ratios compared to other fertilizer treatments. Changes in microbial community composition and enzyme activity were tightly linked to soil C forms. Alkyl-C, carbonyl-C and ketone-C explained most of the variation (> 89%) in soil microbial community, while alkyl-C and ketone-C explained most of the variation (> 91%) in enzyme activity. Our results indicate that C composition rather than C quantity shaped soil microbial community composition and enzyme activity, restricting soil C decomposition. The practice of long-term organic fertilizer use is suggested to increase the quantity and recalcitrance of soil organic C.

Idiopathic non-obstructive azoospermia (INOA) is one of the most severe forms of male infertility, yet its pathophysiology remains unclear. WT1 (Wilm's tumor 1) regulates the polarity of Sertoli cells, thereby playing a critical, indirect role in spermatogenesis. Here, we evaluated WT1 gene variation associates with INOA by assessing its promoter and coding regions in 200 patients diagnosed with INOA and 200 proven fertile men. Three novel variants in the WT1 coding region were detected only in INOA patients, including two synonymous variants and one missense variant, p.Phe435Leu (p.F435L), which was predicted to be deleterious to protein function. The results of dual luciferase reporter showed that the WT1 p.F435L variant decreases transcription of COL4A1 and WNT4 promoters through a dominant-negative effect. Furthermore, chromatin immunoprecipitation assays revealed that COL4A1 and WNT4 promoter is directly bound by wild-type WT1 protein, but not the p.F435L WT1 variant. Thus, we identified a novel functional variant of WT1 functionally associated with INOA. This article is protected by copyright. All rights reserved

Additional file 1: Supporting material.

Objective Colorectal cancer (CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China. Methods From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan (CNY) using 2011 values. Results Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stage-I cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval (95% CI): 37,282−38,522], and the annual average increase rate was 9.2% from 2002 to 2011 (P for trend

This study aimed to evaluate anxiety, depression and quality of life (QoL) by patients' self-report scales and the predictive factors for their aggravation in muscle invasive bladder cancer (MIBC) patients receiving adjuvant chemotherapy. One hundred and ninety-four MIBC patients who received adjuvant chemotherapy and underwent radical cystectomy were consecutively enrolled. HADS was used to evaluate anxiety and depression, and EORTC QLQ-C30 Scale was used to assess QoL. Post adjuvant chemotherapy, HADS-Anxiety score (P = 0.042), anxiety percentage (P = 0.036), HADS-Depression score (P < 0.001), depression percentage (P = 0.002) and the EORTC QLQ-C30 Functional score (P = 0.002) were elevated compared with baseline. Age (P < 0.001), BMI (P = 0.021) and hypertension (P = 0.001) correlated with aggravation of HADS-Anxiety score, while gender (P < 0.001) correlated with aggravation of HADS-Depression score independently during adjuvant chemotherapy. And smoking, alcohol use, hypertension, diabetes, ECOG performance, pT stage as well as pN stage independently predicted the worsening of EORTC QLQ-C30 Scale subscale scores during adjuvant chemotherapy (all P < 0.05). In conclusion, patients' self-report anxiety and depression were increased while QoL was not deteriorated in MIBC patients during adjuvant chemotherapy, and age, gender, BMI, hypertension, smoking, alcohol use, diabetes, ECOG performance, pT stage as well as pN stage were potential predicting factors for their aggravation.

In acid pickling and electroplating processes, a large number of acid droplets, such as sulfuric droplets and hydrochloric droplets, are emitted from the open tank surface. These two types of droplets are typical indoor pollutants in industrial buildings. They are harmful to personnel, devices, and structures. To effectively remove droplets and evaluate their damage to indoor environments, it is important to accurately predict the evaporation and motion of droplets. Partial vapor pressure at the droplet surface significantly affects droplet evaporation and motion. Hence, in this study, the applicability of different droplet surface partial vapor pressure models on the evaporation and motion prediction of two droplets was numerically investigated. Two widely used models, namely osmotic coefficient method and Van't Hoff factor method, were studied for predicting droplet behavior in a free-falling process. The results indicated that the Van't Hoff factor method exhibited a large deviation in predicting the evaporation and motion of the two droplets. The osmotic coefficient method could accurately predict the evaporation and motion of hydrochloric droplets. However, the prediction of sulfuric droplets demonstrated a sharp change (data mutation), thereby resulting in serious deviation. Furthermore, the results indicated that the conditions that led to data mutation corresponded to a relative humidity less than 62% and a solute mass fraction (ω) greater than 40%. Additionally, different ionization methods of sulfuric solution affected the accuracy of the prediction results. The results can provide guidance for the accurate prediction of the evaporation and motion of sulfuric and hydrochloric droplets.

This study was aimed to investigate the influence of pomegranate peel polyphenols (PPPs) on the proliferation and apoptosis of HepG2 cells (a kind of human hepatoma cells) and the related mechanism. The inverted fluorescence microscope and the flow cytometer (FCM) were used to test the changes of the cellular morphology, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial transmembrane potential (Δψm). The kit was used to measure the activities of caspase-3/9, and Western Blot was used to detect the expressions of apoptosis-associated proteins including p53, Bcl-2/Bax, Cyt-c and PARP. The results showed that the cells cycle of HepG2 arrested at the S-phase by PPPs and the amount of the early apoptotic cells and ROS level were increased obviously, the level of Cyt-c and the activity of Caspase-3/9 markedly were also increased by PPPs, as well as the ratio of Bax/Bcl-2 and the protein expressions of P53. It was concluded that PPPs could inhibit the growth of HepG2 cells by blocking the cell cycle and inducing the mitochondrial apoptotic pathway in a dose-dependent manner.

Background Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects. Findings A total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were captured and sequenced using a next generation sequencing platform from Complete Genomics and Illumina. Single Nucleotide Polymorphism and small Insertion/deletion variants were defined and analyzed. We developed a semi-automatic interpretation pipeline which enables accurate variants classification. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Conclusions Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.

In the power system, the dispatcher’s inappropriate execution commands often have great impact on the safe operation and might lead to accidents. In order to further study the risk mechanism of human factors and calculate the human error probability (HEP), this paper proposes a hybrid risk analysis method called SD-SPAR (a System Dynamic Model for the Standardized Plant Analysis Risk (SPAR) Method), which combines the SPAR Human Reliability Analysis method with the System Dynamic (SD) approach to initialize a framework to model dynamic relationships between the Performance Shaping Factors (PSFs) and HEP. First of all, to reduce the uncertainty of grade division for the PSF stress and make the result of HEP more accurate, a physiological factor measurement method was adopted to calculate the dispatcher workload and help to divide the stress quantitatively. Second, based on the SD-SPAR method, the path dependence between the PSFs were summarized to reveal their influence on HEP and successful performance. Third, by analyzing the causality and feedback mechanism of the internal factors, the reasons accounting for incidents can be found to help analysts have a deeper understanding about the incidents, and to move forward improvement strategies to decrease the human error risk so as to achieve better task performance. This study can also be used to form the basis for the simulation of various control scenarios. It can help to explore better solutions to prevent and correct human error behaviors, and guarantee the safe operation of the power system.