•The compression curves of undisturbed loess have normalizable characteristics.•A new method for calculating the loess collapsibility index is proposed.•The calculated value of the new method is ...closer to the field-measured value.
Collapsibility affects loess engineering stability. Currently, there are two methods used to determine the collapsibility of loess: the traditional indoor collapsibility test (indoor test) method and the field immersion test (field test) method. However, for the same loess site, the collapse values under overburden pressure obtained by the two methods are quite different. For sites that cannot be tested in situ, it is easy to misjudge the collapsibility of the loess foundation when depending only on indoor test results. To improve the accuracy of the indoor collapsibility determination, the characteristics of the compression curves obtained from confined compression tests at six different loess sites are analyzed in this paper. The compression curves of loess under different states are normalized and described by the composite power exponential model. The collapsibility of loess is closely related to its structure. A new method for analyzing and evaluating the collapsibility of loess is proposed; the method combines the relationship between the compression characteristics and initial structural properties of loess and the relationship between the initial structural properties and physical comprehensive indexes. To verify the applicability and accuracy of the new method, the collapse values under overburden pressure of two test sites along the Xi'an Metro Line 5 were calculated using the physical indexes of loess at different depths and compared with the values calculated from the indoor test and field-measured values. The results show that the calculated value of the new method is closer to the measured value of the field test than is the calculated value of the indoor test, and the new method can correctly determine the collapsibility type and grade of the site. The new method provides a simple and feasible means by which to correctly and quickly evaluate site collapsibility in loess engineering, which is beneficial for conducting loess site collapsibility evaluations under full operation to develop and implement the measures of foundation treatment in loess areas. The method can be used as a reference at loess sites where field tests cannot be performed.
Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies
; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients ...with hepatocellular carcinoma
. The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis)
. Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. Sertraline suppressed mTOR signalling, and selective drugs that target this pathway were highly effective in causing the apoptotic cell death of hepatocellular carcinoma cells treated with a CDC7 inhibitor. The feedback reactivation of mTOR signalling after its inhibition
is blocked in cells that have been treated with a CDC7 inhibitor, which leads to the sustained inhibition of mTOR and cell death. Using multiple in vivo mouse models of liver cancer, we show that treatment with combined inhibition of of CDC7 and mTOR results in a marked reduction of tumour growth. Our data indicate that exploiting an induced vulnerability could be an effective treatment for liver cancer.
Hepatocellular carcinoma (HCC)-the most common form of liver cancer-is an aggressive malignancy with few effective treatment options
. Lenvatinib is a small-molecule inhibitor of multiple receptor ...tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit
. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR) by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.
The accurate description of the stress-strain relationships of rock and soil is very important to analyze its mechanical properties, but the forms of stress-strain curves are different, which can be ...softening, hardening, or ideal elastoplastic. With the change of confining pressure, they can be transformed into each other. Taking one of loess as the research object, consolidated drained triaxial tests of undisturbed loess under different confining pressures are carried out. The stress-strain relationship obtained is described by the composite power exponential model (CPE model). According to the results, the critical confining pressure during the transformation of the stress-strain curve and the stress-strain relationship under a given confining pressure are predicted. The comparison with the experimental data shows that the CPE model has high accuracy in description and prediction, and the predicted critical confining pressure can correctly judge the type of stress-strain curve of undisturbed loess under different confining pressures. The predicted ideal elastic-plastic stress-strain curve and the curves under given confining pressures conform to the curve change law, which can reflect the real characteristics of loess. Finally, the stress-strain curves of coral clay, silica sand and cement mortar are described and predicted by the CPE model, and then compared with the experimental data. The high consistency between the two further verifies the wide applicability of the CPE model. It provides a method to infer the results under other conditions from a limited number of test results, which will help to correctly analyze the mechanical properties of loess, clay, sand, cement mortar and other materials in practical projects, and to be realized in numerical analysis.
•The stress-strain relationship can be described and predicted by the composite power exponential model (CPE model).•The prediction methods of critical confining pressure and ideal elastic-plastic stress-strain curve are proposed.•The CPE model is applicable not only to loess, but also to other materials with similar stress-strain relationship.
•Medium residue polysaccharide (RPS) from Cordyceps militaris SU-12 was isolated.•Glycosidic bond types and Molecular weight were characterized.•Three monosaccharide components of RPS were ...confirmed.•Antihyperlipidemic and hepatoprotective activities were investigated in vivo.•Antioxidant analysis of RPS in vivo was processed.
Cordyceps militaris has been artificially cultivated in China, and the great amounts of produced medium residue were discarded after the harvest. The aims of this work were to analyze the structure of the residue polysaccharide (RPS) of C. militaris SU-12, and to investigate the pharmacological effects of RPS on lipid metabolism and oxidative stress. RPS was composed of glucose, arabinose and mannose with a ratio of 62:1.6:1 by gas chromatography analysis, and the Mw (weight-average molecular weight), Mn (number-average molecular weight) and Mz (z-average molecular weight) of RPS were 2.86×103, 6.85×102, and 1.97×104Da, respectively. The mice experiments demonstrated that RPS could reduce the levels of blood and liver lipid, and improve the glutamate pyruvate transaminase and antioxidant activity. The histopathological observations of mice livers indicated that RPS could attenuate liver cell injury. Results suggest that the RPS might be used as a potential antihyperlipidemic, hepatoprotective and antioxidant product.
Abstract
Objective
The study sought to review recent literature regarding use of speech recognition (SR) technology for clinical documentation and to understand the impact of SR on document accuracy, ...provider efficiency, institutional cost, and more.
Materials and Methods
We searched 10 scientific and medical literature databases to find articles about clinician use of SR for documentation published between January 1, 1990, and October 15, 2018. We annotated included articles with their research topic(s), medical domain(s), and SR system(s) evaluated and analyzed the results.
Results
One hundred twenty-two articles were included. Forty-eight (39.3%) involved the radiology department exclusively and 10 (8.2%) involved emergency medicine; 10 (8.2%) mentioned multiple departments. Forty-eight (39.3%) articles studied productivity; 20 (16.4%) studied the effect of SR on documentation time, with mixed findings. Decreased turnaround time was reported in all 19 (15.6%) studies in which it was evaluated. Twenty-nine (23.8%) studies conducted error analyses, though various evaluation metrics were used. Reported percentage of documents with errors ranged from 4.8% to 71%; reported word error rates ranged from 7.4% to 38.7%. Seven (5.7%) studies assessed documentation-associated costs; 5 reported decreases and 2 reported increases. Many studies (44.3%) used products by Nuance Communications. Other vendors included IBM (9.0%) and Philips (6.6%); 7 (5.7%) used self-developed systems.
Conclusion
Despite widespread use of SR for clinical documentation, research on this topic remains largely heterogeneous, often using different evaluation metrics with mixed findings. Further, that SR-assisted documentation has become increasingly common in clinical settings beyond radiology warrants further investigation of its use and effectiveness in these settings.
Introduction The autonomy-supportive coaching style is recognized for its positive impact on athletes’ well-being and performance. However, the transition of excessive autonomy into a laissez-faire ...coaching style has not been thoroughly examined within the context of coach evaluation scales. Existing scales focus predominantly on the positive dimensions of autonomy support, and do not possess the capabilities to measure outcomes which may be viewed as negative or other outcomes. This study aims to integrate the autonomy-supportive and laissez-faire coaching styles within the same measurement framework. Methods Our study developed a comprehensive scale to assess both the autonomy-supportive and laissez-faire coaching styles, drawing on items from the Sport Climate Questionnaire for autonomy support and adapting items from leadership research for laissez-faire coaching. We conducted two studies: the first with 148 athletes to refine the laissez-faire items and the second with 460 athletes to validate the full scale, utilizing exploratory factor analysis, confirmatory factor analysis, and correlation analysis. We also measured internal consistency and split-half reliability. Results The finalized scale includes a 6-item autonomy-supportive subscale and a 5-item laissez-faire subscale. Validation processes confirmed the scale’s construct and criterion validity, alongside its reliability. Discussion The Chinese Coaches’ Autonomy-Supportive— Laissez-Faire Coaching Style Scale effectively captures both the beneficial and potentially detrimental aspects of coaching styles, addressing a critical gap in the literature and providing a reliable tool for evaluating coaching approaches.
Cellular senescence is characterized as a stable proliferation arrest that can be triggered by multiple stresses. Most knowledge about senescent cells is obtained from studies in primary cells. ...However, senescence features may be different in cancer cells, since the pathways that are involved in senescence induction are often deregulated in cancer. We report here a comprehensive analysis of the transcriptome and senolytic responses in a panel of 13 cancer cell lines rendered senescent by two distinct compounds. We show that in cancer cells, the response to senolytic agents and the composition of the senescence-associated secretory phenotype are more influenced by the cell of origin than by the senescence trigger. Using machine learning, we establish the SENCAN gene expression classifier for the detection of senescence in cancer cell samples. The expression profiles and senescence classifier are available as an interactive online Cancer SENESCopedia.
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•Senescent cancer cells respond differently to senolytic ABT-263•SASP expression in cancer is heterogeneous and influenced by cell origin•The SENCAN classifier detects cancer cell senescence in vitro•The Cancer SENESCopedia contains transcriptome data from 37 senescence models
Jochems et al. define common vulnerabilities of senescent cancer cells and shared features for the unequivocal detection of cancer cell senescence. Comprehensive analysis in a cancer cell panel reveals the context dependency of cancer cell senescence and allows the establishment of a SENCAN classifier to detect cancer cell senescence.
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•ERK2 inhibition was identified as an enhancer of the response to sorafenib in HCC.•Selumetinib increases the response of sorafenib in HCC cell lines with high p-ERK.•The synthetic ...lethal effect is derived from synergistic inhibition of ERK kinase.•The combination therapy is most likely to be effective in tumors with high p-ERK.
Treatment of liver cancer remains challenging because of a paucity of drugs that target critical dependencies. Sorafenib is a multikinase inhibitor that is approved as the standard therapy for patients with advanced hepatocellular carcinoma, but it only provides limited survival benefit. In this study we aimed to identify potential combination therapies to improve the clinical response to sorafenib.
To investigate the cause of the limited therapeutic effect of sorafenib, we performed a CRISPR-Cas9 based synthetic lethality screen to search for kinases whose knockout synergizes with sorafenib. Synergistic effects of sorafenib and selumetinib on cell apoptosis and phospho-ERK (p-ERK) were analyzed by caspase-3/7 apoptosis assay and western blot, respectively. p-ERK was measured by immunochemical analysis using a tissue microarray containing 78 liver cancer specimens. The in vivo effects of the combination were also measured in two xenograft models.
We found that suppression of ERK2 (MAPK1) sensitizes several liver cancer cell lines to sorafenib. Drugs inhibiting the MEK (MEK1/2 MAP2K1/2) or ERK (ERK1/2 MAPK1/3) kinases reverse unresponsiveness to sorafenib in vitro and in vivo in a subset of liver cancer cell lines characterized by high levels of active p-ERK, through synergistic inhibition of ERK kinase activity.
Our data provide a combination strategy for treating liver cancer and suggest that tumors with high basal p-ERK levels, which are seen in approximately 30% of liver cancers, are most likely to benefit from such combinatorial treatment.
Sorafenib is approved as the standard therapy for patients with advanced hepatocellular carcinoma, but only provides limited survival benefit. Herein, we found that inhibition of the kinase ERK2 increases the response to sorafenib in liver cancer. Our data indicate that a combination of sorafenib and a MEK inhibitor is most likely to be effective in tumors with high basal phospho-ERK levels.
The mixed-lubrication model of the planetary roller screw is proposed considering contact load, contact geometry of thread, surface roughness and transient effects. The influences of rotational speed ...of the screw, axial load and surface roughness on lubrication are discussed. Increasing rotational speed has a significant effect on the lubrication of contact areas. As the speed increases, the film thickness increases while the friction coefficient and contact-area ratio decrease, and the lubrication mode changes from mixed to full-film. As the load increases, the film-thickness ratio decreases while the friction coefficient and maximum subsurface von Mises stress increase. High-precision machining can improve lubrication by properly reducing the roughness of the machined surface, which would increase film thickness and decrease the contact-area ratio.
•Load distribution across the threads of planetary roller screw is calculated.•The mixed-lubrication model of the planetary roller screw is proposed.•Rotational speed of the screw has a significant influence on the frictional behaviors.•Overload causes the lubrication worsening and reduces the life of planetary roller screw.•The lubrication mode of thread interface changes as the root mean square roughness increases.
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