Summary
During the past 30 years, with the possible biggest population with chronic HBV infection in the world, the physicians and scientists in China have unique experience in the fight against HBV. ...Even though some drugs are not recommended anymore, but this kind of experience are very helpful for the development of new medicine and strategy against HBV.
Seasonal forecasts using coupled ocean–atmosphere climate models are increasingly employed to provide regional climate predictions. For the quality of forecasts to improve, regional biases in climate ...models must be diagnosed and reduced. The evolution of biases as initialized forecasts drift away from the observations is poorly understood, making it difficult to diagnose the causes of climate model biases. This study uses two seasonal forecast systems to examine drifts in sea surface temperature (SST) and precipitation, and compares them to the long-term bias in the free-running version of each model. Drifts are considered from daily to multi-annual time scales. We define three types of drift according to their relation with the long-term bias in the free-running model: asymptoting, overshooting and inverse drift. We find that precipitation almost always has an asymptoting drift. SST drifts on the other hand, vary between forecasting systems, where one often overshoots and the other often has an inverse drift. We find that some drifts evolve too slowly to have an impact on seasonal forecasts, even though they are important for climate projections. The bias found over the first few days can be very different from that in the free-running model, so although daily weather predictions can sometimes provide useful information on the causes of climate biases, this is not always the case. We also find that the magnitude of equatorial SST drifts, both in the Pacific and other ocean basins, depends on the El Niño Southern Oscillation (ENSO) phase. Averaging over all hindcast years can therefore hide the details of ENSO state dependent drifts and obscure the underlying physical causes. Our results highlight the need to consider biases across a range of timescales in order to understand their causes and develop improved climate models.
Forkheadbox protein 3 (FOXP3), initially identified as a key transcription factor for regulatory T cells (Treg cells), was also expressed in many tumors including pancreatic ductal adenocarcinoma ...(PDAC). However, its role in PDAC progression remains elusive. In this study, we utilized 120 PDAC tissues after radical resection to detect cancer-FOXP3 and Treg cells by immunohistochemistry and evaluated clinical and pathological features of these patients. Cancer-FOXP3 was positively correlated with Treg cells accumulation in tumor tissues derived from PDAC patients. In addition, high cancer-FOXP3 expression was associated with increased tumor volumes and poor prognosis in PDAC especially combined with high levels of Treg cells. Overexpression of cancer-FOXP3 promoted the tumor growth in immunocompetent syngeneic mice but not in immunocompromised or Treg cell-depleted mice. Furthermore, CCL5 was directly trans-activated by cancer-FOXP3 and promoted the recruitment of Treg cells from peripheral blood to the tumor site in vitro and in vivo. This finding has been further reinforced by the evidence that Treg cells recruitment by cancer-FOXP3 was impaired by neutralization of CCL5, thereby inhibiting the growth of PDAC. In conclusion, cancer-FOXP3 serves as a prognostic biomarker and a crucial determinant of immunosuppressive microenvironment via recruiting Treg cells by directly trans-activating CCL5. Therefore, cancer-FOXP3 could be used to select patients with better response to CCL5/CCR5 blockade immunotherapy.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
With increased global warming, cyanobacteria are blooming more frequently in lakes and reservoirs, severely damaging the health and stability of aquatic ecosystems and threatening drinking water ...safety and human health. There is an urgent demand for the effective prediction and prevention of cyanobacterial blooms. However, it is difficult to effectively reduce the risks and loss caused by cyanobacterial blooms because most methods are unable to successfully predict cyanobacteria blooms. Therefore, in this study, we proposed a new cyanobacterial bloom occurrence prediction method to analyze the probability and driving factors of the blooms for effective prevention and control. Dominant cyanobacterial species with bloom capabilities were initially determined using a dominant species identification model, and the principal driving factors of the dominant species were then analyzed using canonical correspondence analysis (CCA). Cyanobacterial bloom probability was calculated using a newly-developed model, after which, the probable mutation points were identified and thresholds for the principal driving factors of cyanobacterial blooms were predicted. A total of 141 phytoplankton data sets from 90 stations were collected from six large-scale hydrology, water-quality ecology, integrated field surveys in Jinan City, China in 2014–2015 and used for model application and verification. The results showed that there were six dominant cyanobacterial species in the study area, and that the principal driving factors were water temperature, pH, total phosphorus, ammonia nitrogen, chemical oxygen demand, and dissolved oxygen. The cyanobacterial blooms corresponded to a threshold water temperature range, pH, total phosphorus (TP), ammonium nitrogen level, chemical oxygen demand, and dissolved oxygen levels of 19.5–32.5 °C, 7.0–9.38, 0.13–0.22 mg L−1, 0.38–0.63 mg L−1, 10.5–17.5 mg L−1, and 4.97–8.28 mg L−1, respectively. Comparison with research results from other global regions further supported the use of these thresholds, indicating that this method could be used in habitats beyond China. We found that the probability of cyanobacterial bloom was 0.75, a critical point for prevention and control. When this critical point was exceeded, cyanobacteria could proliferate rapidly, increasing the risk of cyanobacterial blooms. Changes in driving factors need to be rapidly controlled, based on these thresholds, to prevent cyanobacterial blooms. Temporal and spatial scales were critical factors potentially affecting the selection of driving factors. This method is versatile and can help determine the risk of cyanobacterial blooms and the thresholds of the principal driving factors. It can effectively predict and help prevent cyanobacterial blooms to reduce the global probability of occurrence, protect the health and stability of water ecosystems, ensure drinking water safety, and protect human health.
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•Our method can analyze probability and driving factors before cyanobacteria bloom occur.•Studies from other regions approved our method and results.•Probability of 0.75 is a critical point for cyanobacteria bloom prevention.•It can effectively predict cyanobacteria blooms and help reduce occurrence risk.
Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors ...(TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study.
Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis.
EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments.
EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and 'second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.
Emerging chemotherapy drugs and targeted therapies have been widely applied in anticancer treatment and have given oncologists a promising future. Nevertheless, regeneration and recurrence are still ...huge obstacles on the way to cure cancer. Cancer stem cells (CSCs) are capable of self-renewal, tumor initiation, recurrence, metastasis, therapy resistance, and reside as a subset in many, if not all, cancers. Therefore, therapeutics specifically targeting and killing CSCs are being identified, and may be promising and effective strategies to eliminate cancer. MicroRNAs (miRNAs, miRs), small noncoding RNAs regulating gene expression in a post-transcriptional manner, are dysregulated in most malignancies and are identified as important regulators of CSCs. However, limited knowledge exists for biological and molecular mechanism by which miRNAs regulate CSCs. In this article, we review CSCs, miRNAs and the interactions between miRNA regulation and CSCs, with a specific focus on the molecular mechanisms and clinical applications. This review will help us to know in detail how CSCs are regulated by miRNAs networks and also help to develop more effective and secure miRNA-based clinical therapies.
•Simple, robust, efficient and fully explicit algorithm for phase field fracture model.•The explicit algorithm overcomes difficulties concerning the convergence.•The explicit algorithm facilitates ...the calculation of the anisotropic material tensor.•Introduction of the concept of phase field modulus.•New linear tetrahedra element with displacement gradient average scheme.
In this paper, we propose an explicit phase field model for dynamic brittle fracture. The mechanical field is integrated with a Verlet-velocity scheme, while the phase field is incremented with sub-steps at each step. The sub-stepping is adaptive based on the phase field residual and fast convergence is obtained in a few sub-steps. The numerical difficulty in convergence and the calculation of anisotropic stiffness tensor in the implicit phase field model are avoided in the explicit scheme. The explicit phase field model uses the phase field modulus, rather than the conventional phase field viscosity. The proposed scheme can achieve the same result by the implicit dynamic scheme phase field model. Several numerical examples are presented to validate the explicit method.
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