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Precise stratification of patients into homogeneous disease subgroups could address the heterogeneity of phenotypes and enhance understanding of the pathophysiology underlying specific subtypes. Existing literature on subtyping patients with major depressive disorder (MDD) mainly utilized clinical features only. Genomic and imaging data may improve subtyping, but advanced methods are required due to the high dimensionality of features.
Methods
We propose a novel disease subtyping framework for MDD by integrating brain structural features, genotype-predicted expression levels in brain tissues, and clinical features. Using a multi-view biclustering approach, we classify patients into clinically and biologically homogeneous subgroups. Additionally, we propose approaches to identify causally relevant genes for clustering.
Results
We verified the reliability of the subtyping model by internal and external validation. High prediction strengths (PS) (average PS: 0.896, minimum: 0.854), a measure of generalizability of the derived clusters in independent datasets, support the validity of our approach. External validation using patient outcome variables (treatment response and hospitalization risks) confirmed the clinical relevance of the identified subgroups. Furthermore, subtype-defining genes overlapped with known susceptibility genes for MDD and were involved in relevant biological pathways. In addition, drug repositioning analysis based on these genes prioritized promising candidates for subtype-specific treatments.
Conclusions
Our approach successfully stratified MDD patients into subgroups with distinct clinical prognoses. The identification of biologically and clinically meaningful subtypes may enable more personalized treatment strategies. This study also provides a framework for disease subtyping that can be extended to other complex disorders.
Broadband frequency-tripling pulses with high energy are attractive for scientific research, such as inertial confinement fusion, but are difficult to scale up. Third-harmonic generation via nonlinear frequency conversion, however, remains a trade-off between bandwidth and conversion efficiency. Based on gradient deuterium deuterated potassium dihydrogen phosphate (KDxH2-xPO4, DKDP) crystal, here we report the generation of frequency-tripling pulses by rapid adiabatic passage with a low-coherence laser driver facility. The efficiency dependence on the phase-matching angle in a Type-II configuration is studied. We attained an output at 352 nm with a bandwidth of 4.4 THz and an efficiency of 36%. These results, to the best of our knowledge, represent the first experimental demonstration of gradient deuterium DKDP crystal in obtaining frequency-tripling pulses. Our research paves a new way for developing high-efficiency, large-bandwidth frequency-tripling technology.
The assessment of seed quality and physiological potential is essential in seed production and crop breeding. In the process of rapid detection of seed viability using tetrazolium (TZ) staining, it is necessary to spend a lot of labour and material resources to explore the pretreatment and staining methods of hard and solid seeds with physical barriers. This study explores the TZ staining methods of six hard seeds (Tilia miqueliana, Tilia henryana, Sassafras tzumu, Prunus subhirtella, Prunus sibirica, and Juglans mandshurica) and summarizes the TZ staining conditions required for hard seeds by combining the difference in fat content between seeds and the kinship between species, thus providing a rapid viability test method for the protection of germplasm resources of endangered plants and the optimization of seed bank construction. The TZ staining of six species of hard seeds requires a staining temperature above 35 °C and a TZ solution concentration higher than 1%. Endospermic seeds require shorter staining times than exalbuminous seeds. The higher the fat content of the seeds, the lower the required incubation temperature and TZ concentration for staining, and the longer the staining time. And the closer the relationship between the two species, the more similar their staining conditions become. The TZ staining method of similar species can be predicted according to the genetic distance between the phylogenetic trees, and the viability of new species can be detected quickly.
The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about under the reasonable assumption of constant mass density.
To comprehensively study the physical properties of inductively coupled plasma (ICP), a finite element method (FEM) simulation model of ICP is developed using the well-established COMSOL software. To benchmark the validation of the FEM model, two key physical parameters, the electron density and the electron temperature of the ICP plasma, are precisely measured by the state-of-the-art laser Thomson scattering diagnostic approach. For low-pressure plasma such as ICP, the local pressure in the generator tube is difficult to measure directly. The local gas pressure in the ICP tube has been calibrated by comparing the experimental and simulation results of the maximum electron density. And on this basis, the electron density and electron temperature of ICP under the same gas pressure and absorbed power have been compared by experiments and simulations. The good agreement between the experimental and simulation data of these two key physical parameters fully verifies the validity of the ICP FEM simulation model. The experimental verification of the ICP FEM simulation model lays a foundation for further study of the distribution of various physical quantities and their variation with pressure and absorption power, which is beneficial for improving the level of ICP-related processes.
Several studies have been conducted on collision avoidance (CA) and path planning for maritime autonomous surface ships (MASS) based on artificial potential field (APF) and electronic navigation chart (ENC) data. However, to date, accurate, highly efficient, and automatic modelling of complicated geometry environment potential fields (EPFs) has not been realised. In this study, an accurate EPF model is established using ENC data to describe different types of obstacles, navigable areas, and non-navigable areas. The implicit equations of complex polygons are constructed based on the R-function theory, and the discrete-convex hull method is introduced to realise the automatic modelling of EPF. Moreover, collaborative CA and obstacle avoidance (OA) experiments are designed and conducted in a simulated environment and based on the ENC data. The results show that the proposed EPF modelling method is accurate, reliable, and time-efficient even with numerous ENC data and complex shapes owing to the R-function representation for geometric objects and discrete-convex hull method. The combination of improved APF and EPF models is proven to be effective for CA and OA. This paper presents a practical EPF modelling approach for APF-based ship path planning.
Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
Aims
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
Method
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
Results
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
Conclusions
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
We report the results of a longitudinal intervention with students across 5 universities in China designed to reduce online consumer debt. We allocate participants to either a financial literacy treatment group, a self-control treatment group, or a zero-touch control group. Our self-control training intervention features detailed tracking of spending and borrowing, budgeting, and introspection about consumption choices. This intervention reduces online borrowing and delinquency charges, mainly driven by a reduction in entertainment-related spending and borrowing. In contrast, financial literacy interventions improve test scores but only marginally affect borrowing. Our results suggest that cultivating self-regulation and budgeting skills can improve borrowing behavior on e-commerce platforms.
To explore if there is association between vitamin D supplementation through cod liver oil ingestion around the periconceptional period and the risk of developing severe CHD in offspring. Furthermore, we would examine the interaction between vitamin D and folic acid supplementation in the association.
Methods:
A case–control study was conducted in Shanghai Children’s Medical Center, in which, a total of 262 severe CHD cases versus 262 controls were recruited through June 2016 to December 2017. All children were younger than 2 years. To reduce potential selection bias and to minimise confounding effects, propensity score matching was applied.
Results:
After propensity score matching, vitamin D supplementation seemed to be associated with decreased odds ratio of severe CHD (odds ratio = 0.666; 95% confidence intervals: 0.449–0.990) in the multivariable conditional logistic analysis. Furthermore, we found an additive interaction between vitamin D and folic acid supplementation (relative excess risk due to interaction = 0.810, 95% confidence intervals: 0.386–1.235) in the association.
Conclusion:
The results suggested that maternal vitamin D supplementation could decrease the risk of offspring severe CHD; moreover, it could strengthen the protective effect of folic acid. The significance of this study lies in providing epidemiological evidence that vitamin D supplementation around the periconceptional period could be a potential nutritional intervention strategy to meet the challenge of increasing CHD.
To detect the abnormal behaviour of ships in the waters of any jurisdiction and to improve the safety of maritime navigation, the meshing-based method is adopted to obtain discrete trajectory data and a probabilistic directed graph model is established to obtain historical data from ships' AIS (automatic identification systems). The state statistical characteristics of each node in the ship probability map are obtained to detect the navigation state of the ship in real time. By predicting the normal navigation trajectory of the ship, it can be judged whether the ship has the potential to behave abnormally at some moment in the future. Simulation experiments were designed based on a maritime simulator platform. The experimental results indicate that the model can correctly predict abnormal behaviour by ships, including excessive speed and deviation from the channel or normal sailing mode.
This paper presents new LA-ICP-MS zircon U–Pb chronology, whole-rock geochemical and zircon Hf isotopic data for the felsic lavas of the Huili Group from the southwestern Yangtze Block. LA-ICP-MS zircon U–Pb dating shows that these rocks were emplaced in Late Mesoproterozoic time (∼1028 to 1019 Ma). Relative to typical I-type and S-type granitoids, all the samples are characterized by low Sr and Eu, and high high-field-strength element contents, high TFeO/MgO, enriched rare earth element compositions and negative Eu anomalies, indicating that they share the geochemical signatures of A-type granitoid. They can be further divided into two groups: Group I and Group II. Group I are A1-type felsic rocks and were produced by fractional crystallization of alkaline basaltic magmas. The Group II felsic lavas belong to the A2-type and were derived by partial melting of a crustal source with mixing of mantle-derived magmas. Both Group I and Group II felsic lavas may erupt in a continental back-arc setting. The coexistence of A1- and A2-type rocks in the southwestern Yangtze Block suggests that they can occur in the same tectonic setting.
This paper presents a real-time and deterministic path planning method for autonomous ships or Unmanned Surface Vehicles (USV) in complex and dynamic navigation environments. A modified Artificial Potential Field (APF), which contains a new modified repulsion potential field function and the corresponding virtual forces, is developed to address the issue of Collision Avoidance (CA) with dynamic targets and static obstacles, including emergency situations. Appropriate functional and safety requirements are added in the corresponding virtual forces to ensure International Regulations for Preventing Collisions at Sea (COLREGS)-constrained behaviour for the own ship's CA actions. Simulations show that the method is fast, effective and deterministic for path planning in complex situations with multiple moving target ships and stationary obstacles and can account for the unpredictable strategies of other ships. The authors believe that automatic navigation systems operated without human interaction could benefit from the development of path planning algorithms.
The present study was undertaken to investigate the antiparasitic activity of extracellular products of Streptomyces albus. Bioactivity-guided isolation of chloroform extracts affording a compound showing potent activity. The structure of the compound was elucidated as salinomycin (SAL) by EI-MS, 1H NMR and 13C NMR. In vitro test showed that SAL has potent anti-parasitic efficacy against theronts of Ichthyophthirius multifiliis with 10 min, 1, 2, 3 and 4 h (effective concentration) EC50 (95% confidence intervals) of 2.12 (2.22–2.02), 1.93 (1.98–1.88), 1.42 (1.47–1.37), 1.35 (1.41–1.31) and 1.11 (1.21–1.01) mg L−1. In vitro antiparasitic assays revealed that SAL could be 100% effective against I. multifiliis encysted tomonts at a concentration of 8.0 mg L−1. In vivo test demonstrated that the number of I. multifiliis trophonts on Erythroculter ilishaeformis treated with SAL was markedly lower than that of control group at 10 days after exposed to theronts (P < 0.05). In the control group, 80% mortality was observed owing to heavy I. multifiliis infection at 10 days. On the other hand, only 30.0% mortality was recorded in the group treated with 8.0 mg L−1 SAL. The median lethal dose (LD50) of SAL for E. ilishaeformis was 32.9 mg L−1.
We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60–<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.
A compact dual-wideband (DWB) bandpass filter utilizing open-shorted coupled lines (OSCL) is proposed in this paper. The introduction of the folded structure not only reduces the overall size but also contribute to the split of the transmission zero (TZ), which improves the selectivity effectively. Six transmission poles and five TZs are realized utilizing the shorted-circuit stub and OSCL. The characteristic of the flexible adjustment method of TZs guarantees an independently wide adjustable range of the bandwidth. For demonstration, a DWB filter (3 dB bandwidth 120 and 28%, respectively) is designed and fabricated. The filter is compact and has the characteristics of extraordinary wide bandwidth, low insertion loss, as well as high selectivity.
Heading angle is a vital parameter in maintaining a vessel's track along a planned course and should be guaranteed in a stable and reliable way. An innovative method of heading determination based on a fisheye camera, which is almost totally unaffected by electromagnetism and geomagnetism, is proposed in this paper. In addition, unlike traditional astronomical methods, it also has a certain degree of adaptability to cloudy weather. Utilising the super wide Field Of View (FOV) of the camera, it is able to simultaneously image the Moon and the horizon. The Moon is treated as the observed celestial body and the horizon works as the horizontal datum. Two experiments were conducted at sea, successfully proving the feasibility of this method. The proposed heading determination system has the merits of automation, resistance to interference and could be miniaturised, making application viable.
Jurassic sandstones in the Xiongcun porphyry copper–gold district, southern Lhasa subterrane, Tibet, China were analysed for petrography, major oxides and trace elements, as well as detrital zircon U–Pb and Hf isotopes, to infer their depositional age, provenance, intensity of source-rock palaeo-weathering and depositional tectonic setting. This new information provides important evidence to constrain the tectonic evolution of the southern Lhasa subterrane during the Late Triassic – Jurassic period. The sandstones are exposed in the lower and upper sections of the Xiongcun Formation. Their average modal abundance (Q21F11L68) classifies them as lithic arenite, which is also supported by geochemical studies. The high chemical index of alteration values (77.19–85.36, mean 79.96) and chemical index of weathering values (86.19–95.59, mean 89.98) of the sandstones imply moderate to intensive weathering of the source rock. Discrimination diagrams based on modal abundance, geochemistry and certain elemental ratios indicate that felsic and intermediate igneous rocks constitute the source rocks, probably with a magmatic arc provenance. The detrital zircon ages (161–243 Ma) and εHf(t) values (+10.5 to +16.2) further constrain the sandstone provenance as subduction-related Triassic–Jurassic felsic and intermediate igneous rocks from the southern Lhasa subterrane. A tectonic discrimination method based on geochemical data of the sandstones, as well as detrital zircon ages from sandstones, reveals that the sandstones were most likely deposited in an oceanic island-arc setting. These results support the hypothesis that the tectonic background of the southern Lhasa subterrane was an oceanic island-arc setting, rather than a continental island-arc setting, during the Late Triassic – Jurassic period.
Children acquiring sociolinguistic knowledge in transnational migration settings must learn to evaluate multiple languages and dialects in a fluid, multifaceted social landscape. This study examines the sociolinguistic development of local and expatriate children in Singapore and investigates the extent to which they share sociolinguistic knowledge and norms. One hundred fourteen children ages five to nineteen completed a region identification task and an occupation judgment task, focusing on their perception of four regional English varieties: Australian English, Northern-China-accented English, Filipino English, and Singapore English. While all groups performed well on the region identification task, expatriate children outperformed locals within the youngest age group. Singaporean and expatriate children attending local schools showed greater familiarity with local norms than international school students in their occupation ratings. Participants mapped speakers to occupations by general prestige level, suggesting that children rely on indirect knowledge of social status rather than direct experience with speakers in their development of sociolinguistic evaluation. (Children's sociolinguistic development, transnational migration, language attitudes)*
A stalagmite with high 238U content from Yangkou Cave, China, revealed the evolution of the Asian summer monsoon (ASM) between 49.1 and 59.5 ka, and the δ18O values recorded Dansgaard/Oeschger (D/O) events 13–17. The Yangkou record shows a relatively gradual transition into the D/O 14 and 16 events. The discrepancy between the abrupt and gradual transitions of D/O 14 in the records from northern and southern China, respectively, suggests different responses of the ASM to climate changes in the high northern latitudes. The higher resolution δ18O record and more precise 230Th dating indicate that the timing of D/O 14 and 17 in the Hulu records at 53 and 58 ka should be shifted to 54.3 and 59 ka, respectively. The gradual strengthening of the ASM at the onsets of D/O 16 and 14 in our record is different from the abrupt temperature rise in the northern high latitudes. Some other factors must contribute to this relatively gradual ASM change in southern China, but the actual reason is still unknown.
The depositional history of the lower Yangtze River and sea-level changes during Marine Oxygen Isotope Stage (MIS) 3 was established using three long drill cores from the northern Yangtze deltaic plain and southern Yellow Sea by using sedimentary analysis and AMS 14C dates. Voluminous channel deposits of the lower Yangtze River in MIS 3 were found from the northern deltaic plain and offshore area, with a thickness of over 30 m. The thick channel deposits are characterized by massive medium-to-fine sand deposits with sporadic tidal influence. During MIS 3, the Yangtze River appears to have mainly migrated between the modern river mouth and middle Jiangsu coastal plain, and likely built a delta complex in the field of Yangtze Sand Shoal in northern East China Sea. A large sediment supply and rapid sea-level variations promoted rapid progradation of the delta onto the flat shelf. The highest sea levels during MIS 3 are estimated to have reached 25 ± 5 m below the present sea level.