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Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Direct numerical simulation of spanwise-rotation-driven flow transitions in viscoelastic plane Couette flow from a drag-reduced inertial to a drag-enhanced elasto-inertial turbulent flow state followed by full relaminarization is reported for the first time. Specifically, this novel flow transition begins with a drag-reduced inertial turbulent flow state at a low rotation number $0\leqslant Ro \leqslant 0.1$, and then transitions to a rotation/polymer-additive-driven drag-enhanced inertial turbulent regime, $0.1\leqslant Ro \leqslant 0.3$. In turn, the flow transitions to a drag-enhanced elasto-inertial turbulent state, $0.3\leqslant Ro \leqslant 0.9$, and eventually relaminarizes at $Ro=1$. In addition, two novel rotation-dependent drag enhancement mechanisms are proposed and substantiated. (1) The formation of large-scale roll cells results in enhanced convective momentum transport along with significant polymer elongation and stress generated in the extensionally dominated flow between adjacent roll cells at $Ro\leqslant 0.2$. (2) Coriolis-force-generated turbulent vortices cause strong incoherent transport and homogenization of significant polymer stress in the bulk via their vortical circulations at $Ro=0.5 - 0.9$.
The flow physics of inertio-elastic turbulent Taylor–Couette flow for a radius ratio of $0.5$ in the Reynolds number ($Re$) range of $500$ to $8000$ is investigated via direct numerical simulation. It is shown that as $Re$ is increased the turbulence dynamics can be subdivided into two distinct regimes: (i) a low $Re \leqslant 1000$ regime where the flow physics is essentially dominated by nonlinear elastic forces and the main contribution to transport and mixing of momentum, stress and energy comes from large-scale flow structures in the bulk region and (ii) a high $Re \geqslant 5000$ regime where inertial forces govern the flow physics and the flow dynamics is mainly governed by small-scale flow structures in the near-wall region. Flow–microstructure coupling analysis reveals that the elastic Görtler instability in the near-wall region is triggered via significant polymer extension and commensurately high hoop stresses. This instability gives rise to small-scale elastic vortical structures identified as elastic Görtler vortices which are present at all $Re$ considered. In fact, these vortices develop herringbone streaks near the inner wall that have a longer average life span than their Newtonian counterparts due to their elastic origin. Examination of the budgets of mean streamwise enstrophy, mean kinetic energy, turbulent kinetic energy and Reynolds shear stress demonstrates that increasing fluid inertia hinders the generation of elastic stresses, leading to a monotonic reduction of the elastic-related effects on the flow physics.
The present study aimed to explore the association between dietary patterns in abdominal obesity obtained by reduced-rank regression (RRR) with visceral fat index (VFI) as a dependent variable and dyslipidemia in rural adults in Henan, China. A total of 29538 people aged 18–79 were selected from the Henan Rural Cohort Study. RRR analysis was used to identify dietary patterns; logistic regression analysis and restricted cubic spline regression models were applied to analyze the association between dietary patterns in abdominal obesity and dyslipidemia. VFI was used as a mediator to estimate the mediation effect. The dietary pattern in abdominal obesity was characterized by high carbohydrate and red meat intake and low consumption of fresh fruits, vegetables, milk, etc. After full adjustment, the highest quartile of dietary pattern scores was significantly associated with an increased risk of dyslipidemia (OR: 1·33, 95 % CI 1·23–1·44, Ptrend < 0·001), there was a non-linear dose–response relationship between them (Poverall-association < 0·001, Pnon-lin-association = 0·022). The result was similar in dose-response between the dietary pattern scores and VFI. The indirect effect partially mediated by VFI was significant (OR: 1·07, 95 % CI 1·06–1·08). VIF explained approximately 53·3 % of odds of dyslipidemia related to the dietary pattern. Abdominal obesity dietary pattern scores positively affected VFI and dyslipidemia; there was a dose-response in both relationships. Dyslipidemia progression increased with higher abdominal obesity dietary pattern scores. In addition, VFI played a partial mediating role in relationship between abdominal obesity dietary pattern and dyslipidemia.
The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
This study aimed to investigate the environmental contamination of nucleic acid at 2019 novel coronavirus (2019-nCOV) vaccination site and to evaluate the effect of improvement to the vaccination process. Nucleic acid samples were collected from the surface of the objects in 2019-nCOV vaccination point A (used between 15 November 2020 and 25 December 2020) and point B (used after 27 December 2020) in a comprehensive tertiary hospital. Samples were collected from point A before improvement to the vaccination process, and from point B (B1 and B2) after improvement to the vaccination process. The real-time fluorescence polymerase chain reaction method was used for detection. The positive rate of vaccination room was 47.06% (24/51) at point A. No positive result was found in point B1 both at working hours (0/27) and after terminal disinfection (0/27). In point B2, the positive results were found in vaccine's outer packaging and staff gloves at working hours, with a positive rate of 7.41% (2/27). The positive rate was 0 (0/27) after terminal disinfection in point B2. The nucleic acid contamination in the vaccination room of 2019-nCOV vaccine nucleic acid sampling point is serious, which can be avoided through the improvement and intervention (such as personal protection, vaccination operation and disinfection methods).
The objective of this study was to delineate the characteristics and incidence of congenital heart disease (CHD) in patients with isolated microtia and to determine whether the prevalence of CHD among patients with isolated microtia increases with the severity of microtia.
A total of 804 consecutive patients had a pre-operative colour Doppler echocardiographic examination. A retrospective study was performed with the clinical and imaging data from November, 2017 to January, 2019. The χ2 test was performed to analyse the interaction between isolated microtia and CHD.
With the colour Doppler echocardiographic examination’s data from 804 consecutive isolated microtia patients, we found CHD, including atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, and others, occurred in 52 of 804 patients (6.5%). Atrial septal defect prevalence in patients with isolated microtia was significantly higher than ventricular septal defect (24/804 versus 11/804, p < 0.05) and patent ductus arteriosus (24/804 versus 2/804, p < 0.001). Ventricular septal defect prevalence in patients with isolated microtia was significantly higher than patent ductus arteriosus (11/804 versus 2/804, p < 0.05). All four types of microtia (concha-type microtia, small concha-type microtia, lobule-type microtia, and anotia) had similar incidences of CHD with no difference in the incidences among these types (p > 0.05 respectively). Furthermore, there was no significant difference in the incidence of the atrial septal defect among the four subtypes (p > 0.05 respectively). Similarly, ventricular septal defect and patent ductus arteriosus also showed no differences (p > 0.05 respectively).
The overall incidences of CHD and three most common CHD subtypes (atrial septal defect, ventricular septal defect, and patent ductus arteriosus) in patients with isolated microtia are higher than general population. The prevalence of CHD among patients with isolated microtia does not increase with the severity of microtia. According to our experience in this study, we suggest colour Doppler echocardiographic imaging should be performed for isolated microtia patients soon after birth if possible. Furthermore, for the plastic surgeon and anaesthesiologist, it is important to take pre-operative colour Doppler echocardiographic images which can help evaluate heart function to ensure the safety of the peri-operative period. Future studies when investigating CHDs associated with isolated microtia could focus on genetic and molecular mechanisms.
The accurate prediction of turbulent mixing induced by Rayleigh–Taylor (R–T), Richtmyer–Meshkov (R–M) and Kelvin–Helmholtz (K–H) instabilities is very important in understanding natural phenomena and improving engineering applications. In applications, the prediction of mixing with the Reynolds-averaged Navier–Stokes (RANS) equation remains the most widely used method. The RANS method involves two aspects, i.e. physical modelling and model coefficients. Generally, the latter is determined empirically; thus, there is a lack of universality. In this paper, inspired by the well-known Reynolds decomposition, we propose a methodology to determine the model coefficients with the following three steps: (i) preset a set of analytical RANS solutions by fully using the knowledge of mixing evolutions; (ii) simplify the differential RANS equations to algebraic equations by imposing the preset solutions to RANS equations; (iii) solve the algebraic equations approximately to give the values of the entire model coefficients. The specific application of this methodology in the widely used K–L mixing model shows that, using the same set of model coefficients determined from the current methodology, the K–L model successfully predicts the mixing evolutions in terms of different physical quantities (e.g. temporal scalings and spatial profiles), density ratios and problems (e.g. R–T, R–M, K–H and reshocked R–M mixings). It is possible to extend this methodology to other turbulence models characterised with self-similar evolutions, such as K-$\epsilon$ mixing models.
Increased intake of vegetables and fruits has been associated with reduced risk of tuberculosis infection. Vegetables and fruits exert immunoregulatory effects; however, it is not clear whether vegetables and fruits have an adjuvant treatment effect on tuberculosis. Between 2009 and 2013, a hospital-based cohort study was conducted in Linyi, Shandong Province, China. Treatment outcome was ascertained by sputum smear and chest computerised tomography, and dietary intake was assessed by a semi-quantitative FFQ. The dietary questionnaire was conducted at the end of month 2 of treatment initiation. Participants recalled their dietary intake of the previous 2 months. A total of 2309 patients were enrolled in this study. After 6 months of treatment, 2099 patients were successfully treated and 210 were uncured. In multivariate models, higher intake of total vegetables and fruits (OR 0·70; 95 % CI 0·49, 0·99), total vegetables (OR 0·68; 95 % CI 0·48, 0·97), dark-coloured vegetables (OR 0·61; 95 % CI 0·43, 0·86) and light-coloured vegetables (OR 0·67; 95 % CI 0·48, 0·95) were associated with reduced failure rate of tuberculosis treatment. No association was found between total fruit intake and reduced failure rate of tuberculosis treatment (OR 0·98; 95 % CI 0·70, 1·37). High intake of total vegetables and fruits, especially vegetables, is associated with lower risk of failure of tuberculosis treatment in pulmonary tuberculosis patients. The results provide important information for dietary guidelines during tuberculosis treatment.
Clonorchis sinensis (C. sinensis) is one of the most serious food-borne parasites, which can lead to liver fibrosis or cholangiocarcinoma. Effective measures for clonorchiasis prevention are still urgently needed. Bacillus subtilis (B. subtilis) is an effective antigen delivery platform for oral vaccines. Chonorchis sinensis serpin (CsSerpin) was proved to be potential vaccine candidates. In this study, CsSerpin3 was displayed on the surface of B. subtilis spore and recombinant spores were orally administrated to BALB/C mice. CsSerpin3-specific IgA levels in faecal, bile and intestinal mucous increased at 4–8 weeks after the first administration compared with those in control groups. The mucus production and the number of goblet cells in intestinal mucosa elevated in B.s-CotC-CsSerpin3 (CotC, coat protein of B. subtilis spore) spores treated group compared to those in blank control. No significant difference in the activities of glutamic-pyruvic transaminase/ alanine aminotransferase and glutamic oxalacetic transaminase/aspartate aminotransferase were observed between groups. There was no side effect inflammation and observable pathological damage in the liver tissue of mice after administration. Moreover, collagen deposition and Ishak score were statistically reduced in B.s-CotC-CsSerpin3 spores treated mice. In conclusion, B. subtilis spores displaying CsSerpin3 could be investigated further as an oral vaccine against clonorchiasis.
In this research communication, a cell model with elevated β-CASEIN synthesis was established by stimulating bovine mammary epithelial cells with 0.6 mM methionine, and the genome-wide gene expression profiles of methionine-stimulated cells and untreated cells were investigated by RNA sequencing. A total of 458 differentially expressed genes (DEGs; 219 upregulated and 239 downregulated) were identified between the two groups. Gene Ontology (GO) analysis showed that the two highest-ranked GO terms in ‘molecular function’ category were ‘binding’ and ‘catalytic activity’, suggesting that milk protein synthesis in methionine-stimulated cells requires induction of gene expression to increase metabolic activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that within the ‘environmental information processing’ category, the subcategory that is most highly enriched for DEGs was ‘signal transduction’. cGMP-PKG, Rap1, calcium, cAMP, PI3K-AKT, MAPK, and JAK-STAT are the pathways with the highest number of DEGs, suggesting that these signaling pathways have potential roles in mediating methionine-induced milk protein synthesis in bovine mammary epithelial cells. This study provides valuable insights into the physiological and metabolic adaptations in cells stimulated with methionine. Understanding the regulation of this transition is essential for effective intervention in the lactation process.
We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (<818·9 μmol/l). Similar trends were found in males and females. Higher plasma Mg levels were associated with a decreased risk of new-onset hyperuricaemia in hypertensive adults.
Pancreatic cancer is currently one of the most lethal tumors because of delayed diagnosis and treatment. Aminopeptidase N (CD13/APN), expressed in pancreatic cancer cells, is closely related to the malignant biological behavior, for instance, angiogenesis formation, tumor proliferation, and metastasis. In this study, asparagine–glycine–arginine (Asn–Gly–Arg, NGR), selectively binding to CD13 receptor, was modified to construct a novel contrast agent of QDs@Gd3+-NGR for targeted diagnosis and treatment of pancreatic cancer. It consists of QDs-unit for fluorescence imaging, Gd3+-unit for magnetic resonance imaging (MRI), and NGR for binding to CD13 receptor. PANC-1 cells labeled by QDs@Gd3+-NGR showed significant red fluorescence and high intensity on fluorescence and MR imaging, respectively. Besides, it was confirmed that QDs@Gd3+-NGR could inhibit theproliferation, metastasis, and invasion of PANC-1 cells, and increase reactive oxygen species production and death rate in vitro. Reasonably, we believe the targeted contrast agent of QDs@Gd3+-NGR can sensitively detect pancreatic cancer via MR-fluorescence dual-modality imaging, and plays an active role in inhibition of tumor progression. The promising results in this study provide integration of diagnostic and therapeutic strategy for the management of pancreatic cancer in future.
This article presents a brief review of our case studies of data-driven Integrated Computational Materials Engineering (ICME) for intelligently discovering advanced structural metal materials, including light-weight materials (Ti, Mg, and Al alloys), refractory high-entropy alloys, and superalloys. The basic bonding in terms of topology and electronic structures is recommended to be considered as the building blocks/units constructing the microstructures of advanced materials. It is highlighted that the bonding charge density could not only provide an atomic and electronic insight into the physical nature of chemical bond of materials but also reveal the fundamental strengthening/embrittlement mechanisms and the local phase transformations of planar defects, paving a path in accelerating the development of advanced metal materials via interfacial engineering. Perspectives on the knowledge-based modeling/simulations, machine-learning knowledge base, platform, and next-generation workforce for sustainable ecosystem of ICME are highlighted, thus to call for more duty on the developments of advanced structural metal materials and enhancement of research productivity and collaboration.
In order to improve the training efficiency and establish a multi-person cooperative training simulation system, including “virtual human,” in the process of virtual reality-based astronaut training, it is necessary to plan the velocity at which astronauts carry the target object. A velocity planning algorithm, combining a traditional six-stage acceleration/deceleration algorithm, based on a time-discrete model with high-order dynamic constraints, considering the elastic damping torque of the space suit, is proposed. The described algorithm is verified on MATLAB to prove its feasibility. Compared to other algorithms, the planning time of the proposed algorithm is significantly reduced.
We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case–control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2–4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose–response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).
Differences in pipe wall microstructure at various positions throughout the wall thickness of high strength aluminum alloy thick-wall pipes produced by reverse hot extrusion were investigated. The microstructures of the inner wall (IW), outer wall (OW), and half wall (HW) were compared. Further, heterogeneity in the mechanical properties of the pipe throughout the wall thickness was also investigated. Results revealed that the volume fraction of precipitation was highest at the HW position because of the higher Zn and Mg contents. Further, approximately 26% of grains were recrystallized in the OW position due to the greater strain during extrusion, while the recrystallization fractions of the IW and HW positions were 13% and 21%, respectively. The effects of precipitation strengthening and deformation strengthening contribute to the highest ultimate tensile strength and Vickers hardness of the HW position, and to the higher elongation of the IW and OW positions.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
GH3536 alloy is one of the high-temperature nickel-based alloys and widely applied in aviation and aerospace industries. In this study, a combination of experiment and simulation is proposed to study the effect of processing parameters on the selective laser melting (SLM) of GH3536 powder. It is concluded that the relationship between density and laser input energy during SLM complies with a quadratic function and presents an inverted U-shaped distribution. By fitting density and input power to a quadratic polynomial, the optimal laser input energy during SLM of GH3536 alloy can be obtained. The result shows that using 275 W laser power and 960 mm/s scanning speed, the SLM GH3536 specimens can reach the maximum density. This experimental result is consistent with the simulation result obtained by analyzing molten pool dimension. Furthermore, a full process energy prediction diagram for SLM GH3536 alloy based on the simulated molten pool depth and width is proposed. The result shows that it provides an innovative and efficient method for the selection of processing parameters during SLM of GH3536 powder.