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As the progress of critical care medicine has improved the survival rate of critically ill patients, comorbidities and long-term health care have attracted people's attention. The terms "post-intensive care syndrome" (PICS) and "PICS-family" (PICS-F) have been used in non-neurocritical care populations, which are characterized by the cognitive, psychiatric, and physical sequelae associated with intensive care hospitalization of survivors and their families. An intensive care unit (ICU) diary authored by the patient's family members may alleviate the psychological distress of the patient and his or her family. This quality improvement project focused on the development and implementation of the pediatric intensive care unit (PICU) diary in the pediatric critical care setting. The project aims to evaluate the feasibility and the potential efficacy of the PICU diary, measured through parental acceptance and satisfaction. Seventeen families of critically ill children admitted to the PICU received the PICU diary during the implementation period. Twenty-four parents completed the weekly follow-up, and 15 subsequently completed the diary entry evaluation. The use of the diary in the PICU setting is feasible and considered beneficial by families of critically ill children.

In this paper a computational cognitive model for decision making based on cost-benefit comparison is presented. For such decision making, it is required that the bene-fits of an option gets weighed against the costs. The brain weighs costs against benefits by combining reward and loss signals in the brain into a single, difference-based neural representation of net value, which is accumulated over time until the individual decides to accept or reject an option. The presented model integrates such findings of the litera-ture and is able to explain a person’s decision making behaviour through several sce-narios. A general parameter setting was found that is used throughout all the simulation scenarios.

In light of the recent advancement in economic narrative analysis, we develop a computational textual analysis method to study economic history. In this method, we collect narrative data from newspapers to measure economic trends. In particular, the popularity (frequency) of a narrative (keyword) on the newspapers is used as the proxy of the amount of economic activities associated with the narrative term; a high frequency indicates that there is a high volume of economic activities associated with the narrative term and vice versa. Regularized regression algorithms are then applied on the narrative frequency data to identify narrative terms whose associated microeconomic activities have macroeconomic impact. We apply the method to study a classic topic in Chinese economic history research: U.S. Silver Purchase Act and the Chinese price level in 1928–1936. Our results provide new insights into this controversial subject. For example, we find that the economic activity associated with the narrative term silver stock had no impact on the Chinese price level, which is contrary to previous research on the topic by Friedman and Schwartz [10]. Meanwhile, economic activities associated with the narrative terms U.S. silver purchase act and silver export are found to have a negative impact on the Chinese price level. This suggests the concerns at that time about the effects of U.S. Silver Purchase Act on the Chinese economy were not misplaced.

The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils., Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease characterized by an immunosuppressive microenvironment. Here the authors show that a subset of P2RX1-negative neutrophils with immunosuppressive properties accumulate in PDAC metastatic liver tissues and promote tumor growth.

This paper digests the influences of financial transparency and media coverage in the Chinese stock market. In China, media performs under a regulatory system and media information is regarded as t...

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8+ T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion–triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T-cell infiltration and a reduced Th1/Th2 ratio. Significance: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.

After studying the principle of ion water atomization, an intelligent humidification system of ion water atomization was designed. The system sensed the external temperature and humidity through the sensor, and built-in intelligent chip to calculate the sensor data. Automatically adjust the amount of ionized water atomization to maintain environmental humidity; Ions can also be added in the atomization humidification process can effectively inhibit the growth of bacteria and eliminate pathogens, this technology has a good practical and practical value.

AIMS Diabetes mellitus is a major cause of death worldwide, including Taiwan. The mortality data of the subsets of patients who suffered from microvascular or macrovascular complications is limited. The aim of this study was to investigate the causes of in-hospital death of patients with type 2 diabetes, especially the patients with microvascular, macrovascular and both micro-macrovascular complications. METHODS A total of 12 159 patients with type 2 diabetes were identified from the Taiwan National Health Insurance Research Database (NHIRD) to analyse the causes of death. Type 2 diabetic subjects with microvascular, macrovascular and both micro-macrovascular complications were further classified and compared to patients without microvascular and macrovascular complications in the logistic regression analysis of the risk of death. RESULTS Pneumonia increased risk of in-hospital death in patients with microvascular, macrovascular and both micro-macrovascular complications, with adjusted odds ratios (AORs) of 2.13 (95% confidence interval [CI] 1.09-4.18), 3.26 (1.71-6.24) and 3.96 (2.17-7.22), respectively. Septicaemia increased risk of in-hospital death in patients with macrovascular (AOR 2.57 [1.31-5.04]) and both micro-macrovascular complications (AOR 4.69 [2.58-8.50]). CONCLUSION Pneumonia increased risk of in-hospital death among the type 2 diabetic patients with microvascular, macrovascular and both micro-macrovascular complications. Therefore, efforts aim at preventing pneumonia or decreasing its severity may increase survival.

This paper digests the relationship between the manipulation of losses and price reversals in the Chinese stock market. Timely loss recognition is involved in detecting the manipulation of losses, while price reversals are investigated by momentum profit. In addition, two-way sorting momentum portfolios are employed to connect manipulating losses with price reversals. Companies with low timely loss recognition aggressively manipulate their losses, and our results indicate that they generate much more significantly negative momentum profits. As a consequence, they cannot build up any immunity against reversal risks and encounter much higher reversal risks than other companies. Such findings still hold after the risk adjustments using asset pricing models come into play and when controlling for the calendar effect. This research indeed suggests that investors should exercise caution when dealing with companies whose financial information is too positive. Such companies may dress up their financial reports, thereby significantly increasing the risks associated with price reversals.

Liver fibrosis occurs during chronic liver disease. Advanced liver fibrosis results in cirrhosis, liver failure and often requires liver transplantation. However, due to the lack of human models, mechanisms underlining the pathogenesis of liver fibrosis remain unclear. Recent studies implicated a central role of deranged lipid metabolism in its pathogenesis. In this study, we generated LEPTIN-deficient (LEPTIN-/-) pigs using zinc finger nuclease technology to investigate the mechanisms of liver fibrosis associated with obesity. The LEPTIN-/- pigs showed increased body fat and significant insulin resistance by 12 months of age. To resemble non-alcoholic fatty liver disease (NAFLD) patients, LEPTIN-/- pig developed the phenotypic features of fatty liver, non-alcoholic steatohepatitis (NASH) and hepatic fibrosis with age. Meanwhile, LEPTIN absence reduced phosphorylation of JAK2-STAT3 and AMPK. The alteration of JAK2-STAT3 enhanced fatty acid β-oxidation, whereas inactivation of AMPK led to mitochondrial autophagy, and both contributed to increased oxidative stress in hepatocytes. Although Leptin deletion in the rat liver altered JAK2-STAT3 phosphorylation, it activated the AMPK pathway and prevented liver fibrogenesis in contrast with the LEPTIN-/- pig. To our knowledge, the LEPTIN-/- pig provides the first model recapitulating the full pathogenesis of NAFLD and its progression toward liver fibrosis. The activity of AMPK signaling pathway suggests a potential target for development of new strategies for the diagnosis and treatment of NAFLD.

Introduction: Alzheimer’s disease (AD) is the most common form of dementia. Eradication of Helicobacter pylori (H. pylori) could affect the incidence and progression of many diseases; however, there are limited studies of the association between H. pylori eradication and AD outcome. We utilized the National Health Insurance Research Database (NHIRD) of Taiwan to determine the relationship between H. pylori eradication and AD in a diabetes mellitus (DM) population.Methods: We collected data from the NHIRD and the Diabetes Mellitus Health Database in Taiwan of patients without a prior diagnosis of AD. We specified three cohorts: patients with (1) peptic ulcer disease (PUD) but no H. pylori treatment, without DM (PUD-HPRx in GP); (2) PUD and DM, but no H. pylori eradication therapy (PUD-HPRx in DM); (3) PUD and DM, with H. pylori eradication therapy (PUD+HPRx in DM). All cohorts were matched according to age, sex, Charlson Comorbidity Index score, and comorbidities.Results: Data were collected from 2000 to 2010, and 157,231 patients were enrolled in total. We compared the effects of treatment for H. pylori infection on the incidence and mortality of AD. The patients with DM who received H. pylori eradication therapy had a higher incidence of AD than the general population (adjusted hazard ratio of incidence [aHR], 1.088). Subgroup analysis showed that the risk of AD was higher in the younger patients who received H. pylori eradication therapy as compared with those who did not (aHR for younger than 45 years, 1.071; aHR of age 45-54 years, 1.089; aHR of age 55-64 years, 1.079) However, a lower mortality rate was observed in the PUD+HPRx in DM group (aHR, 0.945, compared with PUD-HPRx in DM; P < 0.001).Conclusion: In this study, we demonstrated that DM patients who underwent treatment for eradication of H. pylori had a higher incidence of AD, especially younger patients. Nevertheless, there was a lower mortality rate in patients who received H. pylori treatment. Further study is needed to clarify the interrelated roles of AD and eradication therapy for H. pylori.

Background Hepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response. Methods Liver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1−/− mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo. Results Here, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. Meanwhile, CTHRC1 competitively bound to Wnt noncononical receptor and promoted the contractility but not activation of HSCs. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC−/− mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA. Interpretation We demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. Fund This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242, 81802890), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300, 18ZR1436900), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Accurate position detection of indoor objects is crucial for many intelligent life applications and can be realized by various approaches. In certain applications, indoor position detection can be performed using some forms of touch-based floor sensing systems to avoid problems faced by using vision or inertial navigation approaches. The present study develops a floor panel test stage (1 × 1 m2) and its associated localization schemes based on rigid body statics for evaluating the feasibility and the positioning performance on determining the indoor locations of moving objects such as mobile robots. The motion signals are detected by four load cells located at the panel corners and are used to determine the position of the applied forces by means of rigid body statics. Essential tests are performed to examine the system performance. Noticed that due to the existence of boundary reaction moments, traditional predictions based on rigid body statics may not be sufficient and a calibration procedure is required. In parallel, for accommodating different possible scenarios, the corresponding associated localization schemes for estimating the force-applied locations based on the readout history and algorithms are also proposed and realized. The results indicate that the localization accuracy is approximately ± 1 cm over a 1 m span after calibration. Although the method is essentially static, it can still detect object motion provided the motion frequency less than 2 Hz. Furthermore, demonstrations are also presented to highlight other possible applications such as center of gravity measurement of objects and the fusion of multiple localization schemes in indoor environment. Finally, an indoor localization demonstration based on both wiimote IR LED and this smart floor is presented to elucidate the possible application of this work in sensor fusion for indoor motion control.

The overarching view of current tumor therapies simplifies cancer to a cell-biology problem in which neoplasms are caused solely by malignant cells and the exploration of carcinogenesis and tumor progression largely focuses on somatic mutations and other genetic abnormalities of cancer cells. The limited therapeutic response indicates that cancer is driven not only by endogenous oncogenic factors and reciprocal interactions within the tumor microenvironment, but also by complex systemic processes. Homeostasis is the fundamental premise of health, and is maintained by systemic regulation of neuro-endocrine-immune axis. Cancer is also a systemic disease that manifested by dysfunction of the nervous, endocrine, and immune systems. Multiple axes of regulation exist in cancer, including central-, organ-, and microenvironment-level manipulation. At each specific regulatory level, the tridirectional communication among the nervous, endocrine, and immune factors transmit flexible signaling to induce proliferation, invasion, reprogrammed metabolism, therapeutic resistance, and other malignant phenotypes of cancer cells, resulting in the extremely poor prognosis of this lethal disease. Understanding this coordinated signaling network will enable the development of new approaches for cancer treatment via behavioral and pharmacological interventions.

Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.

Background: Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Methods: Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines. ChIP assay and Luciferase reporter assay were used to illustrate the mechanism underlying CD74 induced GDNF expression. Findings: We confirmed that the expression level of CD74 was an independent predictor of PNI and poor prognosis for PDAC. Moreover, we found that upregulation of CD74 on PDAC enhanced its migration and invasive capabilities and potentiated the secretion of neurotrophic factor GDNF to promote the neuroplasticity. Mechanistically, CD74 promoted GDNF production via the AKT/EGR-1/GDNF axis in PDAC. Interpretation: Taken together, our findings suggest a supportive role of CD74 in the PNI of PDAC, and deepen our understanding of how cancer cells promote neuroplasticity in the microenvironment of PDAC. Funding: This work was supported by grants from National Natural Science Foundation of China No.81401931 (Jun-Feng Zhang), 81602414(Jian-Yu Yang), 81702739 (Xue-Liang Fu), 81802317(Min-Wei Yang), and additional grants from Science and Technology funds of School of Medicine, Shanghai Jiao Tong University No. 14XJ10022 (Jun-Feng Zhang), Scientific research project of Shanghai municipal health and Family Planning Commission No. 201740218 (Jun-Feng Zhang). Conflict of Interest: The authors have no conflicts of interest to declare. Ethical Approval: All the patients provided written informed consent before admission, and the study was approved by the Research Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University.

Background: Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Methods: The concentration of sphingosine 1-phosphate (S1P) was detected by high-performance liquid chromatography-tandem mass spectrometry. The Oxygen consumption rate was measured by XF96 metabolic flux analyzer. The interaction between TIM and Specificity protein 1 (Sp1) was confirmed by Co-immunoprecipitation. Chromatin immunoprecipitation and luciferase report assay were performed to demonstrate whether SP1 binds on the Alkaline Ceramidase 2 (ACER2) promotor. Findings: The expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with Sp1 which contributes to upregulate the expression of ACER2. Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Interpretation: Our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81672358, No. 81802890, No. 81172505, No. 81302302). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The SHPD001 and SHPD002 trials were approved by the Independent Ethical Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Before enrollment, all patients signed written informed consent. All animal experiments were approved by the Institutional Animal Care and Use Committee of East China Normal University.

Background: Endometrial cancer (EC) is a common female reproductive system cancer, and obesity is a major risk factor for the disease. ATP-citrate lyase (ACLY), a vital enzyme linking both glycolytic and lipid metabolism, plays important roles in cancer progression. However, there is little evidence of ACLY involvement in EC development. Methods: The ACLY expression in EC was evaluated by using TCGA and GEO databases and verified it using clinical samples by IHC and RT-PCR methods. The functions of ACLY was determined by both the vitro and vivo studies. Gene expression array, co-immunoprecipitation, TUNEL assay, EdU assay, chromatin immunoprecipitation and luciferase reporter assay were applied for mechanism dissection. Findings: ACLY was significantly upregulated in EC patients, particularly in the nucleus. Upregulated ACLY promoted EC cell proliferation and colony formation, and attenuated apoptosis. Mechanistically, cotreatment with obesity-related factors (estradiol, insulin and leptin) promoted nuclear translocation of ACLY through Akt-mediated phosphorylation of ACLY at Ser455 . Nuclear-localized ACLY increased histone acetylation levels, thus resulting in upregulation of pyrimidine metabolism genes, such as DHODH. Moreover, STAT3 altered the ACLY expression at the transcriptional level via directly binding to its promoter region. Interpretation: ACLY nuclear-translocation induced by obesity-related factors promotes EC progression by modulating histone acetylation levels, The ACLY axis could be served as potential therapeutic targets for the treatment of EC. Funding Statement: This research was supported by The National Natural Science Foundation of China (Grant number: 81974406) and The Sailing Program Foundation of Hunan Cancer Hospital. Declaration of Interests: The authors declare that they have no competing interests with the contents of this article. Ethics Approval Statement: The study was approved by the Research Ethics Committee of the Sixth People's Hospital, and informed consent was provided by all patients before this study.

Cassava (Manihot esculenta Crantz) is one of the important staple foods in Sub-Saharan Africa. It produces starchy storage roots that provide food and income for several hundred million people, mainly in tropical agriculture zones. Increasing cassava storage root and starch yield is one of the major breeding targets with respect to securing the future food supply for the growing population of Sub-Saharan Africa. The Cassava Source–Sink (CASS) project aims to increase cassava storage root and starch yield by strategically integrating approaches from different disciplines. We present our perspective and progress on cassava as an applied research organism and provide insight into the CASS strategy, which can serve as a blueprint for the improvement of other root and tuber crops. Extensive profiling of different field-grown cassava genotypes generates information for leaf, phloem, and root metabolic and physiological processes that are relevant for biotechnological improvements. A multi-national pipeline for genetic engineering of cassava plants covers all steps from gene discovery, cloning, transformation, molecular and biochemical characterization, confined field trials, and phenotyping of the seasonal dynamics of shoot traits under field conditions. Together, the CASS project generates comprehensive data to facilitate conventional breeding strategies for high-yielding cassava genotypes. It also builds the foundation for genome-scale metabolic modelling aiming to predict targets and bottlenecks in metabolic pathways. This information is used to engineer cassava genotypes with improved source–sink relations and increased yield potential., The Plant Journal, 103 (5), ISSN:0960-7412, ISSN:1365-313X

Using a serious game for experimental economic research, we obtain insights in how human subjects cope with market and technological uncertainty and their bounded rationality in solving product development challenges. We find not only remarkable differences in the overall performances of cohorts of subjects, but also in the evolution of the product development ‘roadmaps’ across repeated challenges. Generalizing results, we argue that product development engineers may be (1) targeting products for mainstream markets although unknowingly technically unattainable, (2) cognitively overburdened due to combinatorial complexity caused by insufficient technological focus, (3) lacking a contextually sensible ‘product development roadmap’, e.g. taking product design purely as a technical challenge without market requirements. Benchmarking outstanding subjects, preliminary recommendations are to dismiss fast and frugal strategies; the complexity of the design challenge does not lend itself for those. Moreover, during the onset phase of development: engineers are to engage in exploration to determine the technological structure as well as market segmentation. This may then be used to determine the research direction to start focused and hence efficient, depth-first pruning of technological opportunities, which, in turn, reduces combinatorial complexity.

The Chinese stock market is one of the markets where price reversal easily takes place in the world. Its opening has been accelerating. However, this market has plenty of shortcomings, some of which involve China’s special corporate culture. Artificial manipulations in financial reports are prevalent, which gives rise to uncertainties of investments. We propose turnover, financial transparency, and media coverage in the discussion of Chinese momentum. In so doing, we investigate the reasons for price reversal. We find that portfolio with high turnover usually has high financial transparency but it easily encounters price reversal. By contrast, the portfolio with high media coverage is free of price reversal even if these stocks have relatively low transparency and turnover.

Big data technology enables us to access tremendous amounts of information; however, individuals cannot process all available information due to the bounded attention. The impact of this tension upon information seeking and processing behaviors and the resultant decision-making quality is still unclear. By agent-based simulation, we explicitly model the endogenous information choice in a sequential decision-making process, where individuals choose independently how much information and what type of information (shallow information such as the popularity a product, or deep information such as the expected utility of a product) is to be used. It is found that when the information is costly, only a small part of the individuals use deep information and only limited pieces of it, and other individuals simply follow the majority choice. The decrease in the cost of of information cost due to big data can encourage individuals to make use of more information, resulting in a better overall decision quality. However, if the big data only reduces the cost of shallow information but not that of the deep information, the decision quality is diminished because more individuals are induced to adopt the herding strategy.

Background: Gastric cancer (GC) is one of the leading causes of lethal malignancies worldwide, especially in Eastern Asia. Clinical responses to antitumor therapies are often limited to a subset of patients. Methods: To uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we performed ultra-deep targeted sequencing in a cohort with 72 patients (41 with chemotherapy sensitivity and 31 with chemotherapy resistance). Results: We found that sixteen mutated cancer genes were associated with widely used agent in chemotherapy of gastric cancer. Genes identified in these study are mainly involved in activation and inactivation of cancer chemotherapeutic agents, changes of apoptosis and proliferation, drug efflux, DNA damage repair, and the tumor microenvironment. Discussion: A novel group of chemo-sensitivity related genes provided new therapeutic strategies to overcome the development and evolution of resistance to cancer chemotherapy.

The TOUGH suite of nonisothermal multiphase flow and transport simulators has been updated by various developers over many years to address a vast range of challenging subsurface problems. The increasing complexity of the simulated processes as well as the growing size of model domains that need to be handled call for an improvement in the simulator's computational robustness and efficiency. Moreover, modifications have been frequently introduced independently, resulting in multiple versions of TOUGH that (1) led to inconsistencies in feature implementation and usage, (2) made code maintenance and development inefficient, and (3) caused confusion to users and developers. TOUGH3—a new base version of TOUGH—addresses these issues. It consolidates both the serial (TOUGH2 V2.1) and parallel (TOUGH2-MP V2.0) implementations, enabling simulations to be performed on desktop computers and supercomputers using a single code. New PETSc parallel linear solvers are added to the existing serial solvers of TOUGH2 and the Aztec solver used in TOUGH2-MP. The PETSc solvers generally perform better than the Aztec solvers in parallel and the internal TOUGH3 linear solver in serial. TOUGH3 also incorporates many new features, addresses bugs, and improves the flexibility of data handling. Due to the improved capabilities and usability, TOUGH3 is more robust and efficient for solving tough and computationally demanding problems in diverse scientific and practical applications related to subsurface flow modeling.

In this paper, we study the connections between working memory capacity (WMC) and learning in the context of economic guessing games. We apply a generalized version of reinforcement learning, popularly known as the experience-weighted attraction (EWA) learning model, which has a connection to specific cognitive constructs, such as memory decay, the depreciation of past experience, counterfactual thinking, and choice intensity. Through the estimates of the model, we examine behavioral differences among individuals due to different levels of WMC. In accordance with ‘Miller’s magic number’, which is the constraint of working memory capacity, we consider two different sizes (granularities) of strategy space: one is larger (finer) and one is smaller (coarser). We find that constraining the EWA models by using levels (granules) within the limits of working memory allows for a better characterization of the data based on individual differences in WMC. Using this level-reinforcement version of EWA learning, also referred to as the EWA rule learning model, we find that working memory capacity can significantly affect learning behavior. Our likelihood ratio test rejects the null that subjects with high WMC and subjects with low WMC follow the same EWA learning model. In addition, the parameter corresponding to ‘counterfactual thinking ability’ is found to be reduced when working memory capacity is low.

The recent success of PD-1 and PD-L1 blockade in cancer therapy illustrates the important role of the PD-1/PD-L1 pathway in the regulation of antitumor immune responses. However, signaling regulated by the PD-1/PD-L pathway is also associated with substantial inflammatory effects that can resemble those in autoimmune responses, chronic infection, and sepsis, consistent with the role of this pathway in balancing protective immunity and immunopathology, as well as in homeostasis and tolerance. Targeting PD-1/PD-L1 to treat cancer has shown benefits in many patients, suggesting a promising opportunity to target this pathway in autoimmune and inflammatory disorders. Here, we systematically evaluate the diverse biological functions of the PD-1/PD-L pathway in immune-mediated diseases and the relevant mechanisms that control these immune reactions.

Background: Liver is one of the most preferred destinations of distant metastasis in gastric cancer (GC). As effective treatment is still limited, the prognosis of GC patients bearing liver metastasis is poor. We filter out lysyl oxidase (LOX) to study its function in the tumor microenvironment (TME) and seek for potential therapeutic targets. Methods: Transcription analysis on 6 cases of liver metastasis of GC patients with respective paired primary tumors and adjacent normal livers was performed. The filtration out of LOX was done using 5 datasets. 69 GC liver metastasis tissues were utilized to perform immunohistochemistry (IHC) and analyze prognosis. Computed Tomography (CT) combined 3D organ reconstruction bioluminescence imaging was performed to precisely evaluate the metastatic tumor burden on liver of intrasplenic injection mouse model. Human and mouse cancer associated fibroblasts (CAFs) in liver metastasis were separated to culture to study the interaction of LOX and TGF-β1. Patients-derived xenograft (PDX) model was established using liver metastasis of patients to evaluate the therapeutic value of LOX inhibitor β‐aminopropionitrile (BAPN). Results: CAFs-derived LOX at liver metastatic niche of GC promotes niche formation and outgrowth thus predicts poor prognosis. Meanwhile tumor cells in niche secrete TGF-β1 to nourish CAFs and stimulate them to produce more LOX in turn. The mechanism involved in LOX-mediated proliferation facilitation is enhancement of Warburg effect. The inhibitor of LOX, BPAN could hamper the effect brought by LOX in vivo and in vitro. Interpretation: Our study has unveiled a positive feedback loop between CAFs and tumor cells in liver metastasis niche of GC. The core molecule is LOX which facilitates Warburg effect. Targeting LOX with its inhibitor BAPN might serve as a potential therapeutic strategy. Fund: This research was supported by the National Natural Science Foundation of China (31872740), the 100-member plan of the Shanghai Municipal Commission of Health and Family Planning (2017BR043), Shanghai Science and Technology Commission Project(17ZR1416800), Renji Hospital Training Fund (PYMDT-003, PYIII-17–015), National Natural Science Foundation of China (81672358), the Shanghai Municipal Education Commission—Gao feng Clinical MedicineGrant Support (20181708), Program of Shanghai Academic/Technology Research Leader(19XD1403400), Science and Technology Commission of Shanghai Municipality (18410721000), Shanghai Municipal Health Bureau (2018BR32), China Postdoctoral Science Foundation (2018M640403), National Natural Science Foundation of China (81701945) and Youth project of Shanghai Municipal Health Commission(20164Y0045). Keywords: Gastric cancer, Liver metastasis, LOX, CAFs, Warburg effect

Background Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. Objective To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. Method Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. Results Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend Conclusions Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

We study the manipulated information dissemination and risk-adjusted momentum return in the Chinese stock market. In this paper, we employ excess media coverage as a proxy for manipulated information dissemination. The raw momentum returns are negative across all degrees of manipulated information dissemination, but turn into significantly positive after controlling for risks. These outcomes hint that the manipulations of information dissemination contribute to price instabilities, so raw momentum returns are negative but turn into positive owing to risk adjustments. Moreover, we also discover that the stocks with high manipulated information dissemination exhibit big size characteristic and resist market risk well.

Background Gastric cancer is one of the deadliest malignant tumours, with a high incidence in China, and is regulated by aberrantly overexpressed oncogenes. However, existing therapies are insufficient to meet patients’ needs; thus, the identification of additional therapeutic targets and exploration of the underlying mechanism are urgently needed. GPAA1 is the subunit of the GPI transamidase that transfers the GPI anchor to proteins within the ER. The functional impacts of increased expression levels of GPAA1 in human cancers are not well understood. Methods Data mining was performed to determine the pattern of GPAA1 expression and the reason for its overexpression in tumour and adjacent normal tissues. In vitro and in vivo experiments evaluating proliferation and metastasis were performed using cells with stable deletion or overexpression of GPAA1. A tissue microarray established by the Ren Ji Hospital was utilized to analyse the expression profile of GPAA1 and its correlation with prognosis. Western blotting, an in situ proximity ligation assay, and co-immunoprecipitation (co-IP) were performed to reveal the mechanism of GPAA1 in gastric cancer. Results GPAA1 was a markedly upregulated oncogene in gastric cancer due to chromosomal amplification. GPAA1 overexpression was confirmed in specimens from the Ren Ji cohort and was associated with ERBB2 expression, predicting unsatisfactory patient outcomes. Aberrantly upregulated GPAA1 dramatically contributed to cancer growth and metastasis in in vitro and in vivo studies. Mechanistically, GPAA1 enhanced the levels of metastasis-associated GPI-anchored proteins to increase tumour metastasis and intensified lipid raft formation, which consequently promoted the interaction between EGFR and ERBB2 as well as downstream pro-proliferative signalling. Conclusions GPAA1 facilitates the expression of cancer-related GPI-anchored proteins and supplies a more robust platform—the lipid raft—to promote EGFR-ERBB2 dimerization, which further contributes to tumour growth and metastasis and to cancer progression. GPAA1 could be a promising diagnostic biomarker and therapeutic target for gastric cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1218-8) contains supplementary material, which is available to authorized users.

Epithelial ovarian cancer (EOC) is a gynecological malignancy with high morbidity. Treating EOC remains a challenge, as the pathogenesis of this disease remains unclear and chemoresistance is a common occurrence. A number of previous studies have revealed that obesity is closely associated with cancer and leptin, as a link between cancer and obesity, has become a focus of research in recent years. In the present study, survival database analysis demonstrated that leptin expression was associated with poor prognoses in patients treated with platinum and paclitaxel/docetaxel. A cell activity assay demonstrated that leptin reduced the chemosensitivity of ovarian cancer cells to paclitaxel/docetaxel. Furthermore, flow cytometry results revealed that treatment with exogenous leptin reduced the proportion of ovarian cancer cells in G2/M phase, which was significantly elevated following paclitaxel/docetaxel chemotherapy. It was also verified that transcription factor CCAAT/Enhancer Binding Protein α can bind to the upstream promoter region of leptin and activate its transcription in ovarian cancer cells. Together, these results suggest that leptin serves an important role in chemoresistance and may serve as a novel therapeutic target for ovarian cancer in patients treated with platinum and paclitaxel chemotherapy.

Patient survival time generally reflects the tumor progression and represents a key clinical parameter. In this study, using copy-number changes, gene mutations, mRNA expression, and reverse phase protein arrays data in hepatocellular carcinoma (HCC) samples with poor and better clinical outcome profiled by The Cancer Genome Atlas (TCGA), we performed comprehensive molecular characterization of prognosisassociated alterations. Among them, several copy number amplifications and deletions can discriminate HCC patients with poor prognosis from those with better prognosis. Mutated DNAH8 showed a worse prognosisspecific pattern and correlated with a reduced disease-free survival in HCC. By integrating RNA sequencing data, we found that HCC samples with poor prognosis are consistently associated with the up-regulation of cell cycle process, such as chromosome separation, DNA replication, cytokinesis, and etc. At the proteomic level, seven proteins were significantly enriched in samples with poor prognosis, including acetylated α-Tubulin, p62-LCK-ligand, ARID1A, MSH6, B-Raf, Cyclin B1, and PEA15. Acetylated α-Tubulin was frequently expressed in HCC tissues and acted as a promising prognostic factor for HCC. Collectively, these alterations lay a foundation for developing relevant therapeutic strategies and improve our knowledge of the pathogenesis of HCC. Funding Statement: The research was supported by grants from Shanghai Municipal Commission of Health and Family Planning, Key Developing Disciplines Program (No: 2015ZB0501), Shanghai Key disciplines program of Health and Family Planning (No: 2017ZZ02010), Shanghai Sailing Program (No: 17YF1405200), and National Natural Science Foundation of China (81701374). Declaration of Interests: The authors state: "Nothing to report." Ethics Approval Statement: All human samples were obtained with informed consent, and protocols were approved by the ethical review committee of the World Health Organization Collaborating Center for Research in Human Production (authorized by the Shanghai Municipal Government).

Background: Liver is one of the most preferred destinations of distant metastasis in gastric cancer (GC). As effective treatment is still limited, the prognosis of GC patients bearing liver metastasis is poor. We filter out lysyl oxidase (LOX) to study its function in the tumor microenvironment (TME) and seek for potential therapeutic targets. Methods: Transcription analysis on 6 cases of liver metastasis of GC patients with respective paired primary tumors and adjacent normal livers was performed. The filtration out of LOX was done using 5 datasets. 69 GC liver metastasis tissues were utilized to perform immunohistochemistry (IHC) and analyze prognosis. Computed Tomography (CT) combined 3D organ reconstruction bioluminescence imaging was performed to precisely evaluate the metastatic tumor burden on liver of intrasplenic injection mouse model. Human and mouse cancer associated fibroblasts (CAFs) in liver metastasis were separated to culture to study the interaction of LOX and TGF-β1. Patients-derived xenograft (PDX) model was established using liver metastasis of patients to evaluate the therapeutic value of LOX inhibitor β‐aminopropionitrile (BAPN). Results: CAFs-derived LOX at liver metastatic niche of GC promotes niche formation and outgrowth thus predicts poor prognosis. Meanwhile tumor cells in niche secrete TGF-β1 to nourish CAFs and stimulate them to produce more LOX in turn. The mechanism involved in LOX-mediated proliferation facilitation is enhancement of Warburg effect. The inhibitor of LOX, BPAN could hamper the effect brought by LOX in vivo and in vitro. Interpretation: Our study has unveiled a positive feedback loop between CAFs and tumor cells in liver metastasis niche of GC. The core molecule is LOX which facilitates Warburg effect. Targeting LOX with its inhibitor BAPN might serve as a potential therapeutic strategy. Funding Statement: This research is supported by the national natural science foundation of China (31872740), The 100-member plan of the Shanghai municipal commission of health and family planning (2017BR043), Shanghai science and technology commission project (17ZR1416800), Renji hospital training fund (PYMDT-003, PYIII-17-015). National Natural Science Foundation of China (81672358, to Z.-G. Zhang), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20181708, to Z.-G. Zhang), Program of Shanghai Academic/Technology Research Leader (19XD1403400, to Z.-G. Zhang), Science and Technology Commission of Shanghai Municipality (18410721000, to Z.-G. Zhang) and Shanghai Municipal Health Bureau (2018BR32, to Z.-G. Zhang). National Natural Science Foundation of China, No. 81701945. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The whole process of specimen collection and experiment performance were approved by the local ethics committee in Renji Hospital, with all patients’ informed consents.

We investigate the relationship between Google Trends Search Volume Index (SVI) and the average returns of Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX). In particular, we used the aggregate SVI searched by a company’s abbreviated name and by its ticker symbol to conduct our research. The results are very different. While the aggregate SVI of abbreviated names is significantly and positively correlated to the average returns of TAIEX, the aggregate SVI of ticker symbols is not. This gives strong evidence that investors in the Taiwan stock market normally use abbreviated names, not ticker symbols, to conduct Google search for stock information. Additionally, we found the aggregate SVI of small–cap companies has a higher degree of impact on the TAIEX average returns than that of the mid–cap and large–cap companies. Finally, we found the aggregate SVI with an increasing trend also has a stronger positive influence on the TAIEX average returns than that of the overall aggregate SVI, while the aggregate SVI with a decreasing trend has no influence on the TAIEX average returns. This supports the attention hypothesis of Odean [12] in that the increased investors attention, which is measured by the Google SVI, is a sign of their buying intention, hence caused the stock prices to increase while decreased investors attention is not connected to their selling intention or the decrease of stock prices.

We study how financial transparency and media coverage work in the Chinese stock markets. In this paper, transparency means information quantity, while media means information transmission. The market has negative momentum profits no matter how transparency or media coverage changes, which suggests that transparency or media coverage does not work individually in China. High transparency and high media coverage make significantly positive momentum profits, whereas low transparency and low media coverage make significantly negative momentum profits. These outcomes show that transparency and media coverage work jointly in China. Our findings imply that information quantity and transmission are both crucial in China.

In this paper, we carry out a sensitivity analysis for an agent-based model of the use of public resources as manifested by the El Farol Bar problem. An early study using the same model has shown that a good-society equilibrium, characterized by both economic efficiency and economic equality, can be achieved probabilistically by a von Neumann network, and can be achieved surely with the presence of some agents having social preferences, such as the inequity-averse preference or the 'keeping-up-with-the-Joneses' preference. In this study, we examine this fundamental result by exploring the inherent complexity of themodel; specifically, we address the effect of the three key parameters related to size, namely, the network size, the neighborhood size, and the memory size. We find that social preferences still play an important role over all the sizes considered. Nonetheless, it is also found that when network size becomes large, the parameter, the bar capacity (the attendance threshold), may also play a determining role.

This study explores the optimal extraction technology of polysaccharides from dendrobium officinale (DPS). The best combination of extraction parameters was through response surface methodology with a three-variable-three-level Box-Behnken design.

How to achieve a robust performance remains an intractable problem in the various object tracking algorithms due to some unfavorable factors, e.g. occlusions, appearance change, etc. In this paper, a robust object tracking approach is proposed based on a composite similarity measure. Experimental results on several challenging sequences demonstrate the effectiveness and feasibility of the proposed method.

17α-hydroxylase deficiency (17OHD) is a rare disorder of secondary hypertension caused by congenital adrenal hyperplasia. In addition, co-occurrence of an adrenal tumor with 17OHD is extremely rare and easily misdiagnosed. A 33-year-old female with sicca syndrome, persistent hypertension, hypokalemia, and a left adrenal tumor was referred for confirmation of primary aldosteronism. However, the absence of secondary sexual characteristics, persistent growth beyond puberty, and laboratory data of low plasma renin activity, high aldosterone, low cortisol, low sex hormones, elevated adrenocorticotropic hormone, elevated luteinizing hormone, elevated follicle-stimulating hormone, and most importantly, decreased 17-hydroxypregnenolone, supported a diagnosis of 17OHD. We sequenced the CYP17A1 gene of the patient and her parents, which demonstrated genetic defects (D487-S,488-F489 deletion and Y329K418X). 17OHD was diagnosed. The left adrenal tumor was assessed, and a non-functional adrenal incidentaloma was confirmed; NP-59 adrenal cortical scintigraphy and adrenal venous sampling showed no functional activity and non-lateralization. Hormone replacements with estrogen, spironolactone, and prednisolone were given. The patient became more feminized and confident, and her hypertension was controlled. Early diagnosis and treatment of 17OHD not only can prevent delay development of secondary sexual characteristics but also help the patient maintain mental health and improve their quality of life. In addition, the concomitant presence of a left adrenal tumor makes misdiagnosis of a functional adenoma more likely, possibly causing unnecessary surgery and delay inappropriate treatment.

This chapter provides an overview of the current development of big data in the computational social sciences and humanities. It is composed of two parts. In the first part, we review works incorporating the three most frequently seen types of big data, namely geographic data, text corpus data, and social media data, that are used to conduct research on the social sciences in a wide range of fields, including anthropology, economics, finance, geography, history, linguistics, political science, psychology, public health, and mass communications. The second part of the chapter provides a panoramic view of the development of big data in the computational social sciences and humanities, including recent trends and the evoked challenges. As for the former, we review four representative cases of its timely development. They are big data finance, big data in psychology, the spatial humanities, and cloud computing. As for the latter, we present an overview of four challenges associated with big data, namely the complexity of big data or the ontology and epistemology of big data, big data search, big data simulation, and big data risk.

Financial markets are always the most aggressive adopters of new information technologies. The recent boom in big data has enhanced the effect of information diffusion in financial markets since the physical cost of participation has been reduced and interactions among investors have become more efficient. In this chapter, we provide an overview of the current state of the art related to the utilization of big data in financial markets. To start with, we introduce the concept of financial big data from the perspective of complementing our understanding of the predictability and dynamics of financial markets as well as illustrating the changing landscape from conventional media to big data in academic research. Secondly, we summarize the medium effects of financial big data on the efficient market hypothesis and the market dynamics, respectively. Thirdly, we further probe into the underlying mechanisms as to why financial big data exhibits superior predictability and explanatory power for the market dynamics. Finally, this chapter outlines the challenges and promising avenues for future research.

Background: Hepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response. Methods: Liver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1-/- mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo. Results: Here, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC-/- mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA. Interpretation: We demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. Funding Statement: This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242), the Shanghai Municipal Education Commission — Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All of the human materials were obtained with informed content, and protocols were approved by the ethical review committee of the World Health Organization Collaborating Center for Research in Human Production (authorized by the Shanghai Municipal Government). Mice were housed and manipulated according to protocols approved by the East China Normal University Animal Care Commission. All animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences and published by the National Institutes of Health.