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Background 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. Methods 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. Results 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. Conclusions 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.

Silicene is a 2D topological insulator due to its fairly large spin-orbital interaction and features a buckled lattice structure that allows one to control the effective mass of Dirac electrons by a perpendicular electric field. We propose the use of a spatially alternative electric field to generate multiple topologically-protected interface states (TIS) in the bulk silicene. It is shown that when the valley-dependent electron mass (defining the Chern number of an insulating bulk silicene) changes its sign or discontinues due to spatial variation of the electric field, multiple TIS appear in the insulating bulk silicene. The TIS come from the K and valleys and sustain dissipationless valley or spin-valley-dependent currents, which are immune to both the valley-conservation and spin-observation scattering. It is also found that the coupling among TIS due to spatial electron tunneling excites the TIS, and whether there is an excitation gap or not depends on the even or odd TIS number. Our findings may shed light on manufacturing topological electron devices.

This paper presents a novel stochastic optimisation approach to determining the feasible optimal solution of the economic dispatch (ED) problem considering various generator constraints. Many practical constraints of generators, such as ramp rate limits, prohibited operating zones and the valve point effect, are considered. These constraints make the ED problem a non-smooth/nonconvex minimisation problem with constraints. The proposed optimisation algorithm is called self-tuning hybrid differential evolution (self-tuning HDE). The self-tuning HDE utilises the concept of the 1/5 success rule of evolution strategies in the original HDE to accelerate the search for the global optimum. Three test power systems, including 3-unit power systems, 13-unit power systems and 40-unit power systems, are applied to compare the performance of the proposed algorithm with genetic algorithms, the differential evolution algorithm and the HDE algorithm. Numerical results indicate that the entire performance of the proposed self-tuning HDE algorithm outperforms the other three algorithms.

Aims/hypothesis We previously observed hyperglycaemia, hyperinsulinaemia, insulin resistance and obesity in Gpx1-overexpressing mice (OE). Here we determined whether these phenotypes were eliminated by diet restriction, subsequently testing whether hyperinsulinaemia was a primary effect of Gpx1 overexpression and caused by dysregulation of pancreatic duodenal homeobox 1 (PDX1) and uncoupling protein-2 (UCP2) in islets. Methods First, 24 male OE and wild-type (WT) mice (2 months old) were given 3 g (diet-restricted) or 5 g (full-fed) feed per day for 4 months to compare their glucose metabolism. Thereafter, several mechanistic experiments were conducted with pancreas and islets of the two genotypes (2 or 6 months old) to assay for beta cell mass, reactive oxygen species (ROS) levels, mitochondrial membrane potential (Δψm) and expression profiles of regulatory proteins. A functional assay of islets was also performed. Results Diet restriction eliminated obesity but not hyperinsulinaemia in OE mice. These mice had greater pancreatic beta cell mass (more than twofold) and pancreatic insulin content (40%) than the WT, along with an enhanced Δψm and glucose-stimulated insulin secretion in islets. With diminished ROS production, the OE islets displayed hyperacetylation of H3 and H4 histone in the Pdx1 promoter, elevated PDX1 and decreased UCP2. Conclusions/interpretation Overproduction of the major antioxidant enzyme, glutathione peroxidase 1, caused seemingly beneficial changes in pancreatic PDX1 and UCP2, but eventually led to chronic hyperinsulinaemia by dysregulating islet insulin production and secretion.

The relationship between calcium intake and hypertension is receiving increased research attention. The prevalence of hypertension is high among the obese populations. Calcium is a mineral that influences blood pressure. The aim of the study was to examine the association between calcium intake and hypertension in a large nationally representative sample of obese American adults. A total of 14 408 obese adults aged 20 years or older were obtained from the 1999–2010 National Health and Nutrition Examination Survey. Analysis of variance and linear regression models were used to examine relationships between calcium intake and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple logistic regression models were used to examine the association between calcium intake and hypertension after adjusting for potential confounders and interactions, including: age, race, education level, alcohol use, smoking, diabetes status, sodium intake and potassium intake. Calcium intake was significantly lower for the hypertensive group compared with the normotensive group ( P <0.0001), especially among those obese female young adults aged 20–44 years and among non-diabetic obese adults. Based on ordinary linear regression analysis, a significant inverse relationship was detected, SBP and DBP decreased if calcium intake increased (SBP: regression coefficient estimate=−0.015, P <0.0001; DBP: regression coefficient estimate=−0.028, P <0.0001). Multiple logistic regression showed that calcium intake was negatively associated with the probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI): 0.74–0.87, P <0.0001). In stratified analysis, calcium intake in youngest adults (age 20–44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI: 0.64–0.93, P <0.0001), the inverse relationship between calcium intake and probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55–0.84, P <0.0001), when compared with the whole sample including all of 14 408 obese adults. The protective effect of calcium intake and hypertension was found significantly in obese non-diabetic adults (OR: OR=0.77, 95% CI: 0.67–0.89, P <0.0001) not in obese diabetic adults. SBP, DBP and calcium intake were log transformed for both ordinary linear regression analysis and logistic regression analysis. Our study findings underscore the need to explore the physiological mechanism between calcium intake and hypertension. In this study, increased calcium intake was associated with the lowest risk of hypertension. Future studies utilizing longitudinal research designs are needed to quantify therapeutic levels of calcium for control of hypertension among obese adults. Increasing calcium intake among American adults may offer promise as a cost-effective strategy to improve hypertension among obese adults; however, further scientific exploration is warranted.

Defects in the enamelin gene (ENAM) cause amelogenesis imperfecta (AI). Our objective was to identify the genetic etiology of enamel hypoplasia in a Caucasian proband. Our hypothesis was that ENAM was defective. The proband and his father have an AG insertion (g.13185_13186insAG; p.422FsX448) in ENAM previously identified in AI kindreds from Slovenia and Turkey. The proband, his brother, and his mother have a novel missense mutation (g.12573C>T) that substitutes leucine for a phosphorylated serine (p.S216L) in the 32-kDa enamelin cleavage product. In this family, a defect in one ENAM allele caused minor pitting or localized enamel hypoplasia, whereas defects in both alleles caused severe enamel malformations, with little or no mineral covering dentin. Ser216 is one of two serines on the 32-kDa enamelin that is phosphorylated by Golgi casein kinase and is thought to mediate calcium binding. We propose that phosphorylation of enamelin is critical for its function.

Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men, but the molecular mechanism remains obscure. Here, we show that an androgen receptor (AR)-driven oncogene, cell cycle-related kinase (CCRK), collaborates with obesity-induced pro-inflammatory signaling to promote non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Lentivirus-mediated Ccrk ablation in liver of male mice fed with high-fat high-carbohydrate diet abrogates not only obesity-associated lipid accumulation, glucose intolerance and insulin resistance, but also HCC development. Mechanistically, CCRK fuels a feedforward loop by inducing STAT3-AR promoter co-occupancy and transcriptional up-regulation, which in turn activates mTORC1/4E-BP1/S6K/SREBP1 cascades via GSK3β phosphorylation. Moreover, hepatic CCRK induction in transgenic mice stimulates mTORC1-dependent G − csf expression to enhance polymorphonuclear myeloid-derived suppressor cell recruitment and tumorigenicity. Finally, the STAT3-AR-CCRK-mTORC1 pathway components are concordantly over-expressed in human NASH-associated HCCs. These findings unveil the dual roles of an inflammatory-CCRK circuitry in driving metabolic and immunosuppressive reprogramming through mTORC1 activation, thereby establishing a pro-tumorigenic microenvironment for HCC development. Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men. Here the authors find a potential mechanistic explanation by showing that, in mice, obesity-induced STAT3 cooperates with the androgen receptor to activate the mTORC pathway through up regulation of CCRK, resulting in hepatic steatosis worsening and HCC development via metabolic and immune reprogramming.

Although trauma-related symptoms (e.g. complex PTSD and dissociative symptoms) and psychotic symptoms often co-occur, little is known about the complex relationships among these symptoms over time. This study examined the bidirectional relationships among complex PTSD symptoms, dissociative symptoms, and positive symptoms of psychosis. This study analyzed available longitudinal data from two convenience samples (Sample 1:  = 214, Chinese-speaking adults; Sample 2:  = 301, English-speaking adults). Participants in both samples completed validated measures of ICD-11 complex PTSD (that included measurement of 'classical' PTSD), dissociation, and positive symptoms of psychosis at baseline and follow-up, six months (Sample 1) or 12 months (Sample 2) apart. A cross-lagged panel model was used to examine the longitudinal relationship between trauma-related symptoms and psychotic symptoms in each sample. In Sample 1, baseline dissociative symptoms significantly predicted positive symptoms of psychosis at follow-up. In Sample 2, no significant longitudinal relationships between trauma-related and psychotic symptoms were observed. In both samples, baseline disturbances in self-organization (DSO) symptoms predicted 'classical' PTSD symptoms at follow-up. This study made the first attempt to examine the longitudinal relationships among ICD-11 complex PTSD symptoms, dissociative symptoms, and psychotic symptoms. The inconsistent findings point to the importance of further research on the longitudinal relationships between trauma-related and psychotic symptoms. Moreover, our results indicate that addressing DSO symptoms may be important in the prevention and treatment of PTSD symptoms.

Trauma can give rise to mental health problems and emotional and interpersonal difficulties, which in turn can perpetuate the cycle of trauma and adversity for future generations. However, little is known about the prevalence and potential effects of trauma and trauma-related mental health problems among parents. The primary goal of this study was to examine childhood and adulthood trauma and trauma-related symptoms among mothers of children aged between 6 and 18. We also conducted exploratory analyses of their potential relationship with children's emotional and behavioural problems. A total of 817 mothers living with a child aged between 6 and 18 in Taiwan completed standardized self-report assessments of trauma exposure, trauma-related symptoms, and children's emotional and behavioural problems. A subsample (  = 256) also provided follow-up data after six months. Most surveyed mothers reported at least one childhood traumatic event (74.79%) and one adulthood traumatic event (78.70%); 4.4% met the ICD-11 criteria for PTSD, and 12.1% for complex PTSD; 11.4% reported clinically significant dissociative symptoms. Mothers' complex PTSD and dissociative symptoms were cross-sectionally correlated with children's emotional and behavioural problem (rs = .186 to .239,  < .001). After controlling for possible confounding variables and baseline scores, mothers' childhood non-betrayal trauma reported at baseline was found to be a predictor of children's emotional and behavioural problems reported at follow up. This study is the first to provide data regarding childhood and adulthood trauma and trauma-related disorders, including ICD-11 complex PTSD, among mothers in the community. It calls for more studies to understand the potential effects of intergenerational trauma.

Multilayered balloon catheters are attracting more attention in recent years. Multilayered balloon catheters have some unique properties such as meso-/microscale dimensions, small wall thickness, and strict requirements of dimensional accuracy. In this study, three-layered polymeric balloon catheters composed of polyamide, ethylene vinyl acetate, and polypropylene (PA/EVA/PP) are successfully fabricated using a three-layered coextrusion die and the polymer melt flowing behavior through the extrusion die are analyzed. Both the diameter and wall thicknesses have been selected as the targeted structural parameters to investigate the effects of pulling speed, air injection volume rate, and screw speed on the quality of the extrudates. The optimal combination of these three operating conditions has been achieved. It is found that pulling speed can significantly affect the diameters of the extruded balloon catheters. The variation interval values of outer profile diameter and inner cavity diameter with the extrusion experiments are 20.95% and 13.04%, respectively. The screw speed of each layer has a great influence on the wall thickness of each layer. Through the influence of outer screw speed, middle screw speed and inner screw speed, the variation interval values for outer layer wall thickness, middle layer wall thickness, and inner layer wall thickness are 31.06%, 35.69%, and 31.35%, respectively. The air injection volume rate has negligible effect.