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On September 5, 2022, the Luding M6.8 earthquake occurred in the Moxi-Shimian segment of the Xianshuihe fault, coinciding with the historical ruptured zone of the 1786 Moxi earthquake. Its seismogenic environment provides a foundation for comprehending the mechanism of the earthquake and its future hazard. In the Moxi-Shimian segment, we establish a series of near-field Global Navigation Satellite Systems (GNSS) stations to enhance the spatial resolution of observational data for the inversion of the interseismic kinematic parameters. In this study, with an elastic screw dislocation model constrained by GNSS observations, the slip rate of the Moxi-Shimian segment is estimated to be 10.9 ± 1.0 mm/yr, while the locking depth is 15.7 ± 6.2 km. Additionally, we utilize a block-dislocation model to invert the interseismic fault coupling along the Kangding-Moxi-Shimian segment. The result indicates a gradual deepening of the locking depth along the section from Kangding to Shimian. The coseismic rupture of the 2022 event occurred within the high coupling regions in the Kangding-Moxi-Shimian segment, which indicates that the rupture kinematics in this event might be controlled by the interseismic deformation. The seismic moment accumulated within the ruptured zone of the Luding earthquake since 1786 ranges in [1.42–3.40] × 1019 N·m, which is significantly greater than the seismic moment released during the 2022 event. As a result, we infer that the Luding earthquake released only a portion of the accumulated energy within the original rupture zone since 1786, indicating that the 2022 event has not caused a complete rupture in the Moxi-Shimian segment. Consequently, there remains a substantial seismic hazard in this area.

Abstract Background Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential “sparing effects” of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. Methods A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. Results Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (− 0.08 DDE, 95% CI: − 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, − 0.04 DDE, 95% CI: − 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: − 0.009 to 0.12) per patient was noted. Conclusions This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. Highlights • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Abstract Small-field-of-view reconstruction CT images (sFOV-CT) increase the pixel density across airway structures and reduce partial volume effects. Multi-instance learning (MIL) is proposed as a weakly supervised machine learning method, which can automatically assess the image quality. The aim of this study was to evaluate the disparities between conventional CT (c-CT) and sFOV-CT images using a lung nodule system based on MIL and assessments from radiologists. 112 patients who underwent chest CT were retrospectively enrolled in this study between July 2021 to March 2022. After undergoing c-CT examinations, sFOV-CT images with small-field-of-view were reconstructed. Two radiologists analyzed all c-CT and sFOV-CT images, including features such as location, nodule type, size, CT values, and shape signs. Then, an MIL-based lung nodule system objectively analyzed the c-CT (c-MIL) and sFOV-CT (sFOV-MIL) to explore their differences. The signal-to-noise ratio of lungs (SNR-lung) and contrast-to-noise ratio of nodules (CNR-nodule) were calculated to evaluate the quality of CT images from another perspective. The subjective evaluation by radiologists showed that feature of minimal CT value (p = 0.019) had statistical significance between c-CT and sFOV-CT. However, most features (all with p

The etiology of hemorrhagic fever with renal syndrome (HFRS) is significantly impacted by a variety of immune cells. Nevertheless, the existing techniques for sequencing peripheral blood T cell receptor (TCR) or B cell receptor (BCR) libraries in HFRS are constrained by both limitations and high costs. In this investigation, we utilized the computational tool TRUST4 to generate TCR and BCR libraries utilizing comprehensive RNA-seq data from peripheral blood specimens of HFRS patients. This facilitated the examination of clonality and diversity within immune libraries linked to the condition. Despite previous research on immune cell function, the underlying mechanisms remain intricate, and differential gene expression across immune cell types and cell-to-cell interactions within immune cell clusters have not been thoroughly explored. To address this gap, we performed clustering analysis on 11 cell subsets derived from raw single-cell RNA-seq data, elucidating characteristic changes in cell subset proportions under disease conditions. Additionally, we utilized CellChat, a tool for cell–cell communication analysis, to investigate the impact of MIF family, CD70 family, and GALECTIN family cytokines—known to be involved in cell communication—on immune cell subsets. Furthermore, hdWGCNA analysis identified core genes implicated in HFRS pathogenesis within T cells and B cells. Trajectory analysis revealed that most cell subsets were in a developmental stage, with high expression of transcription factors such as NFKB and JUN in Effector CD8+ T cells, as well as in Naive CD4+ T cells and Naive B cells. Our findings provide a comprehensive understanding of the dynamic changes in immune cells during HFRS pathogenesis, identifying specific V genes and J genes in TCR and BCR that contribute to advancing our knowledge of HFRS. These insights offer potential implications for the diagnosis and treatment of this autoimmune disease.

Background:The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients via bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed.Results:Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA.Conclusion:In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.

Background: For patients with atrial fibrillation who have an ischemic stroke or transient ischemic attack (TIA) despite taking direct oral anticoagulants (DOACs), the optimal strategy for ongoing anticoagulation is unknown. Methods: Using provincial administrative databases in Alberta, Canada, we compared anticoagulant use before/after the breakthrough stroke/TIA and assessed recurrence of stroke/TIA or bleeding, with consideration of medication adherence. Adherence was defined as the proportion of days covered (PDC) being ≥ 80%. Results: Among 985 patients, the median age was 80 years (interquartile range 13), with a mean CHADS2 score of 1.7± 1 prior to the index event. Patients were followed for a median of 643 days (interquartile range 836). Following the index stroke/TIA event, 623 patients (63%) filled a prescription for the same DOAC regimen, 83 (8%) filled a prescription for a different dose, 155 (16%) switched DOAC agents, 51 (5%) switched to warfarin, and 73 (7%) filled no oral anticoagulant prescription. Patients who kept the same regimen more commonly had TIA index events (59%); patients who changed dose or drug more often had stroke index events (55%-78%). During follow-up, 135 (14%) had stroke/TIA recurrence, and 46 (5%) had bleeding; rates of each did not differ between prescribing patterns. Post-index event, the proportion of patients with a proportion of days covered ≥ 80% improved from 55% to 80%. Conclusions: Although most maintained the same DOAC regimen after stroke/TIA, rates of recurrent stroke/TIA and bleeding were similar across prescribing patterns. Stroke/TIA severity may have influenced prescribing practices. DOAC prescription adherence improved poststroke/TIA and signals an opportunity for optimization in patients with atrial fibrillation. Résumé: Contexte: Chez les patients atteints de fibrillation auriculaire qui subissent un accident vasculaire cérébral (AVC) ischémique ou un accident ischémique transitoire (AIT) malgré la prise d’anticoagulants oraux directe (AOD), la stratégie optimale pour la poursuite de l’anticoagulation est inconnue. Méthodologie: À partir des bases de données administratives provinciales en Alberta, au Canada, nous avons comparé l’utilisation d’anticoagulants avant/après l’AVC/AIT survenu pendant l’anticoagulothérapie et avons évalué la récurrence d’un AVC/AIT ou d’un saignement, en tenant compte de l’adhésion au traitement médicamenteux. L’adhésion a été définie comme une proportion de jours couverts (PJC) de 80 % ou plus. Résultats: Chez 985 patients, l’âge médian était de 80 ans (écart interquartile de 13) et le score CHADS2 moyen, de 1,7 ± 1 avant l’événement de référence. Les patients ont été suivis pendant une médiane de 643 jours (écart interquartile de 836). Après l’AVC/AIT de référence, 623 patients (63 %) ont fait exécuter une ordonnance du même schéma d’AOD, 83 (8 %) ont fait exécuter une ordonnance d’une dose différente, 155 (16 %) sont passés à d’autres AOD, 51 (5 %) sont passés à la warfarine et 73 (7 %) n’ont fait exécuter aucune ordonnance d’anticoagulant oral. Chez les patients qui ont continué à recevoir le même schéma, la plupart (59 %) avaient eu un AIT comme événement de référence; chez les patients qui ont changé de dose ou de médicament, la plupart (55 à 78 %) avaient eu un AVC comme événement de référence. Durant le suivi, 135 (14 %) ont connu un AVC/AIT récurrent et 46 (5 %) ont présenté un saignement; les taux de chaque manifestation ont été similaires pour les différents schémas de prescription. Après l’événement de référence, le pourcentage de patients ayant une PJC ≥ 80 % a augmenté, passant de 55 à 80 %. Conclusions: Malgré le maintien du même schéma d’AOD chez la plupart des patients après l’AVC/AIT, les taux d’AVC/AIT récurrent et de saignement ont été similaires avec tous les schémas de prescription. La gravité d’un AVC/AIT pourrait avoir influencé les pratiques de prescription. L’adhésion aux AOD prescrits s’est améliorée après un AVC/AIT et témoigne d’une possibilité d’optimisation chez les patients atteints de fibrillation auriculaire.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems and organs, with pulmonary involvement known to be associated with disease prognosis and mortality. Acute lupus pneumonitis (ALP) resembling miliary tuberculosis (TB) is rare. Here, we present a case of ALP mimicking miliary TB and review the literature. A 19-year-old male student was referred to our hospital with fever. Although the patient met the diagnostic criteria for SLE, diffuse miliary nodules in both lungs were observed on a chest computed tomography scan. A series of tests, including pathological testing of bronchoscopy brushes, T-lymphocyte culture + interferon assay (A + B), tuberculin test, detection of mycobacterium TB DNA, and acid-fast bacilli smear in bronchoalveolar lavage fluid, were unable to confirm the presence of TB infection. We considered the patient to have ALP. After beginning ALP therapy, his symptoms disappeared, and the imaging and hematological results returned to normal. Miliary TB and ALP have similar clinical manifestations and imaging changes, which make diagnosis difficult. This case highlights the need to ensure accurate diagnosis and treatment to improve prognosis.

Abstract The valve‐side bushing of the UHV converter transformer is the key equipment in the DC transmission project, and its running state directly affects the security and stability of the power system. This paper analyses the attributes of the physical entities, uses the digital twins to establish the state feature set and proposes a zero‐sample state evaluation algorithm for the valve‐side bushing. First, the geometric, materials and electrical characteristics are analyzed, and the detailed components of carrier current are obtained by empirical mode decomposition. Then, COMSOL is used to establish digital twins, verify the validity of twins with axial heat distribution of bushing, and establish a state feature set with the extreme temperature inside and outside bushing. Finally, the fuzzy clustering algorithm is used to classify the state feature set, and the similarity is used as the index to realize the zero‐sample state evaluation of the valve‐side bushing. Through the demonstration and analysis of examples, the evaluation model solves the problems of difficulty in extracting the internal features, fewer fault samples, and training difficulty, which is conducive to improving the operation and maintenance management level of power transmission equipment.

Abstract To analyze the overheating problem of the valve‐side bushings of high voltage direct current (HVDC) converter transformer, which is mainly caused by current‐carrying connections defects at copper–aluminium transition region in the bushing, this paper set up a 3‐D electromagnetic‐thermal analysis model for the valve‐side bushings, and a method was proposed to calculate the thermal distribution of the valve‐side bushings under the influence of current‐carrying connections defects. Based on this model, the details of an example were shown in this paper, and the numerical results agreed with the measured results within 1%. Then, the temperature field distribution characteristics of valve‐side bushing under different working current I, defect degree k, and ambient temperature Tamb were determined. According to the characteristics, the temperature difference ΔT and working current I of the bushing were applied to evaluate contact resistance at the copper–aluminium transition region of the bushing, which can be provided by a novel method to evaluate for current‐carrying connections defects in the valve‐side bushings.

In China, although drug use is an administrative and not criminal offense, individuals detained by public security authorities are subject to coercive or compulsory “treatment,” which can include community-based detoxification and rehabilitation and two years of compulsory isolation. Individuals are also entered into a system called the Drug User Internet Dynamic Control and Early Warning System, or simply the Dynamic Control System. The Dynamic Control System, run by the Ministry of Public Security, acts as an extension of China’s drug control efforts by monitoring the movement of people in the system and alerting police when individuals, for example, use their identity documents when registering at a hotel, conducting business at a government office or bank, registering a mobile phone, applying for tertiary education, or traveling. This alert typically results in an interrogation and a drug test by police. This paper seeks to summarize, using published government reports, news articles, and academic papers, what is known about the Dynamic Control System, focusing on the procedures of (1) registration; (2) management; and (3) exit. At each step, people subject to the Dynamic Control System face human rights concerns, especially related to the right to privacy, rights to education and work, and right to health.

Estimating and predicting the epidemic size from wastewater surveillance results remains challenging for the practical implementation of wastewater-based epidemiology (WBE). In this study, by employing a highly sensitive detection method, we documented the time series of SARS-CoV-2 RNA occurrence in the wastewater influent from an urban community with a 360,000 population in Japan, from August 2020 to February 2021. The detection frequency of the viral RNA increased during the outbreak events of COVID-19 and the highest viral RNA concentration was recorded at the beginning of January 2021, amid the most serious outbreak event during the study period. We found that: (1) direct back-calculation still suffers from great uncertainty dominated by inconsistent detection and the varying gap between the observed wastewater viral load and the estimated patient viral load, and (2) the detection frequency correlated well with reported cases and the prediction of the latter can be carried out via data-driven modeling methods. Our results indicate that wastewater virus occurrence can contribute to epidemic surveillance in ways more than back-calculation, which may spawn future wastewater surveillance implementations. HIGHLIGHTS Time series of SARS-CoV-2 wastewater presence in a low-prevalence community.; SARS-CoV-2 detection frequency correlates with reported cases.; Reported cases can be predicted by detection frequency within a period.; Data-driven methods may facilitate wastewater-based epidemic modeling.;

Daily runoff is the data to estimate the water resources in a river. In many catchments, the daily discharge is not well observed. Flow duration curve is an important characteristic of daily runoff, and important for the design of water conservancy projects. In the ungauged catchments, the evaluation of distribution functions and the parameters of flow duration curve is a helpful method to understand the characteristics of the flow. This study uses data from 19 hydrological stations to evaluate the applicability of 11 distribution functions to simulate flow duration curves in the northwest of China. The fitted flow duration curves are evaluated by Nash-Sutcliffe efficiency, the root mean square relative error and the coefficient of determination. The evaluation shows that, among the 11 distribution functions, the log normal model is the most suitable model to construct flow duration curves of 19 hydrological stations. Based on a multivariate linear regression model, a regional model of distribution parameters is constructed, including functions of watershed geomorphologic and climatic characteristics. The analysis of Baijiachuan hydrological station shows that the parameters a and b showed a decreasing trend. This study presents an innovative approach to evaluate regionalized parameters of flow duration curves considering the impacts of geomorphologic and climatic characteristics. HIGHLIGHTS Daily discharge at 19 hydrological stations in the northwest of China are used to evaluate the applicability of 11 distribution functions to simulate flow duration curves.; The log normal distribution function is the most suitable model to construct flow duration curves.; A regional model of distribution parameters is constructed, and they are functions of watershed geomorphologic and climatic characteristics.;

Abstract Background The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013 and 2018 in Alberta, Canada. Methods All adult patients defined as chronic opioid users who were authorized medical cannabis by their health care provider in Alberta, Canada from 2013 to 2018 were propensity score matched to non-authorized chronic opioid using controls. A total of 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users. Results Average age was 52 years and 54% were female. Patients on low dose opioids ( 100), showed a significant decrease over 6 months (− 435.5, 95% CI: − 596.8 to − 274.2) compared to controls. Conclusions This short-term study found that medical cannabis authorization showed intermediate effects on opioid use, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME > 100); however, continued surveillance of patients utilizing both opioids and medical cannabis is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.

In this paper, by utilizing fixed-time control technique and a leader-follower control scheme, a three-dimensional (3-D) cooperative guidance law is developed to tackle impact angle constrained simultaneous arrival problem. Firstly, in the line-of-sight (LOS) direction, guidance command for the leader is put forward to make impact time error converge to zero in fixed time such that the leader is capable of reaching the target at prespecified impact time. Then, guidance command for each follower is designed based on information from adjacent interceptors to guarantee each follower's impact time achieves consensus with that of the leader. Secondly, in the azimuth direction and elevation direction of the LOS, guidance commands are put forward to nullify the LOS angular rates within fixed time. Then, the interceptors are able to reach the target with desired impact angles. Meanwhile, the cooperative guidance law's fixed-time convergence is rigorously proved by Lyapunov stability theory. Finally, simulations are given to illustrate the effectiveness of the theoretical results.

Summary: Background: In drug-resistant epilepsy, surgical resection of the epileptic focus can end seizures. However, success is dependent on the ability to identify foci locations and, unfortunately, current methods like electrophysiology and positron emission tomography can give contradictory results. During seizures, glucose is metabolized at epileptic foci through aerobic glycolysis, which can be imaged through the oxygen-glucose index (OGI) biomarker. However, inter-ictal (between seizures) OGI changes have not been studied, which has limited its application. Methods: 18 healthy controls and 24 inter-ictal, temporal lobe epilepsy patients underwent simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) scans. We used [18F]fluorodeoxyglucose-PET (FDG-PET) to detect cerebral glucose metabolism, and calibrated functional MRI to acquire relative oxygen consumption. With these data, we calculated relative OGI maps. Findings: While bilaterally symmetrical in healthy controls, we observed, in patients during the inter-ictal period, higher OGI ipsilateral to the epileptic focus than contralateral. While traditional FDG-PET results and temporal lobe OGI results usually both agreed with invasive electrophysiology, in cases where FDG-PET disagreed with electrophysiology, temporal lobe OGI agreed with electrophysiology, and vice-versa. Interpretation: As either our novel epilepsy biomarker or traditional approaches located foci in every case, our work provides promising insights into metabolic changes in epilepsy. Our method allows single-session OGI measurement which can be useful in other diseases. Funding: This work was supported by ShanghaiTech University, the Shanghai Municipal Government, the National Natural Science Foundation of China Grant (No. 81950410637) and Shanghai Municipal Key Clinical Specialty (No. shslczdzk03403). F. H. and P. H. were supported by USA National Institute of Health grants (R01 NS-100106, R01 MH-067528).Z. W. was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), National Natural Science Foundation of China (No. 82151303), and National Key R&D Program of China (No. 2021ZD0204002).

Abstract Purpose Evaluate the feasibility of fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging in patients with gastric cancer by optimizing the scan protocol and to compare the image quality to 18F FDG PET and computed tomography (CT). Methods The PET/CT and PET/MR imaging were sequentially performed in 30 patients with gastric cancer diagnosed by gastroscope using a single-injection-with-dual-imaging protocol. After intravenous injection of 18F-FDG (mean, 249 MBq), PET/CT imaging including low-dose CT was performed (mean uptake time, 47 ± 6 min), and PET/MR imaging including a T1-weighted Dixon sequence for attenuation correction and two different T2-weighted sequences was subsequently acquired (88 ± 15 min after 18F-FDG injection). Four series of images (CT from PET/CT, T1W, T2W Half-Fourier acquisition single-shot turbo spin-echo [T2W-HASTE] and T2W-BLADE from PET/MR) were visually evaluated using a 3–4 points scale for: (1) image artifacts, (2) lesion conspicuity and (3) image fusion quality. The characteristics of the primary lesions were assessed and compared between the PET/CT and PET/MR acquisitions. Results The image quality and lesion conspicuity of the T2W-HASTE images were significantly improved compared to that of the T2W-BLADE images. A significantly higher number of artifacts were seen in the T2W-HASTE images compared with the T1W and CT images (p 0. 05); however, significant difference was seen in the lesion conspicuity measurements (p

Seeking land use development strategies is an effective policy tool to support economic development, especially in developing countries. Previous studies evidence the indispensable role of urban construction land use (UCLU) in regional economic development. However, neglecting the two-stage characteristic and mismatch of UCLU could misinterpret the strategy. This study, considering a two-stage characteristic, aims to explore how land use development strategy affects economic development. First, we create a measure for UCLU mismatch. Second, using both linear and nonlinear models, we explore the possible relationship between the land use strategy and economic development. Subsequently, robustness and the potential path-dependent reinforcement loop (PDRL) are discussed further. Finally, the fundamental channels are investigated in the mechanism analysis section. The results confirm that temporary positive effects stimulate economic development, whereas permanent potential negative effects undermine robust economic development. In addition, the PDRL shows that irrational adoption of the strategy would mean succumbing to low- and medium-industries. We also find that land and capital demonstrate exogenous properties that function as visible hands, with economic regulation exploring UCLU mismatches and misallocation of resources. However, the overuse of these two policies could lead to an unhealthy cycle of mutually reinforcing adverse effects. Based on these findings, we propose policy recommendations to support the rational use of this strategy.

Objective: We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer’s disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated 11C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value.Methods: Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an 11C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated.Results: Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 ± 0.10 vs. 1.42 ± 0.16 and 1.17 ± 0.08; p < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 ± 0.06 vs. 1.21 ± 0.06; p < 0.0001) and significantly lower than in AD patients (1.66 ± 0.06 vs. 1.86 ± 0.17; p < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 ± 0.02) relative to AD patients (1.05 ± 0.02 vs. 0.99 ± 0.04; p < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR.Conclusion: Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.

Introduction Mutations in the filaggrin ( FLG ) gene are known to cause ichthyosis vulgaris. Methods We used whole-genome sequencing (WGS) technology to investigate the genetic causes of rare and complex inherited diseases including rheumatoid arthritis, ichthyosis, and congenital fibrosis of the extraocular muscles type 1 (CFEOM1) in a Chinese family. WGS was performed in four topics, and the identified candidate mutations were further verified through Sanger sequencing. Results We identified a mutation in FLG gene (g.152280098 C>A, p.E2422∗) that may be associated with ichthyosis and arthritis. Moreover, a mutation in KIF21A (g.39726207 G>A, p.R954 W) was also determined in affected members as the cause of CFEOM1. The gene interaction network demonstrated an interesting correlation between FLG and genes associated with arthritis and ichthyosis. Functional enrichment analysis of these interacting genes revealed several possible pathways that might be linked to arthritis and ichthyosis. Conclusion In general, we confirmed a loss of function mutation in the FLG gene associated with ichthyosis vulgaris and rheumatoid arthritis in this family.

Sediment yield is affected by many factors, such as climate, geology, geomorphology, land use and human activities. Sediment signatures are the statistic indices or curves that are able to effectively describe the temporal and spatial characteristics of sediment transport and evaluate the ability of the streamflow to deliver the sediment. In this study, the sediment signatures of Upper Sangamon River Basin, which is an intensively managed watershed for agriculture development, are analyzed. Firstly, a semi-distributed model of sediment transport is built up based on the Tsinghua Representative Elementary Watershed (THREW) model, and it is applied to Upper Sangamon River Basin. The result of sediment simulation is analyzed by four sediment signatures, i.e. specific sediment yield, sediment delivery ratio, cumulative sediment curve and effective discharge. The sediment signatures are consistent with each other and accord with the fact of the agricultural production in Upper Sangamon River Basin.

Real-time strategy (RTS) game is a kind of strategy game, in which the players compete for resources on 2D terrain by establishing the economy, training army, and guiding them into battle in real time. The winner prediction of the RTS games often involves studying a highly uncertain problem in an adversarial environment. In addition, the limit of the number of samples restricts on the application and performance of the prediction models. To obtain better winner prediction accuracy and maintain the prediction uncertainty under an adversarial environment, this paper proposes a neural network-based prediction method incorporated probability inference dealing with a small set of samples. This paper uses a dataset released based on SC2LE, a reinforcement learning environment released jointly by Blizzard Entertainment and DeepMind, and then employed the proposed neural processes model to build a winner prediction model. To verify, this paper implemented different features types' grouping and different game length grouping experiments for demonstrating better adaptability to such problems. Furthermore, this paper also implemented the SVM model experiments and compared the proposed method with the SVM model. Finally, when making predictions on a 1000 size testing data, the results show that the proposed prediction model achieves an accuracy of 0.811 at 200 and 0.821 at 1000 sizes of training sets, which is better than the SVM model with small training datasets.

Abstract Background Currently, ribosome-binding protein 1 (RRBP1) is considered to be a novel oncogene that is overexpressed in colorectal cancer, lung cancer, mammary cancer, esophageal cancer and other carcinomas. However, the relationship between RRBP1 and endometrioid-type endometrial carcinoma (EC) remains unknown. Our purpose is to explore the function of RRBP1 in endometrioid-type endometrial carcinoma. Methods We investigated the expression of RRBP1 protein by immunohistochemistry on paraffin-embedded surgical specimens from one hundred thirty patients with endometrioid-type endometrial carcinoma. We also evaluated the differences in RRBP1 expression between endometrial cancer samples (n = 35) and normal endometrial tissues (n = 19) by western blotting. Results RRBP1 was more highly expressed in endometrial cancer samples than in normal samples (P

Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are deemed to be the principal causes of MI. Icariside II (ICS II), one of the main active ingredients of Herbal Epimedii, possesses extensive pharmacological activities. However, whether ICS II can protect against MI is still unknown. Therefore, this study was designed to investigate the effect and possible underlying mechanism of ICS II on MI both in vivo and in vitro. The results showed that pretreatment with ICS II not only dramatically mitigated MI-induced myocardial damage in mice but also alleviated H9c2 cardiomyocyte injury elicited by oxygen and glucose deprivation (OGD), which were achieved by suppressing mitochondrial oxidative stress and apoptosis. Furthermore, ICS II elevated the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) expression, thereby activating SIRT3. However, these protective effects of ICS II on MI injury were largely abolished in SIRT3-deficient mice, manifesting that ICS II-mediated cardioprotective effects are, at least partly, due to the presence of SIRT3. Most interestingly, ICS II directly bound with SIRT3, as reflected by molecular docking, which indicated that SIRT3 might be a promising therapeutic target for ICS II-elicited cardioprotection in MI. In conclusion, our findings illustrate that ICS II protects against MI-induced oxidative injury and apoptosis by targeting SIRT3 through regulating the AMPK/PGC-1α pathway.

Abstract Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5’‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics.

ObjectivesThe purpose of this study was to evaluate the feasibility and diagnostic performance of prostate-specific membrane antigen (PSMA) based 18F-DCFPyL PET/CT-ultrasound (PET/CT-US) or PET/MRI-ultrasound (PET/MRI-US) fusion targeted biopsy for intra-prostatic PET-positive lesions.MethodsFrom April 2018 to November 2019, we prospectively enrolled 55 candidates to perform PET/CT-US or PET/MRI-US fusion targeted biopsies for solitary PET-positive prostate lesions (two to four cores/lesion). The positive rates of prostate cancer based on patients and biopsy cores were calculated respectively. With reference to the pathological results of biopsy cores, the MR signal characteristics in the area of the PET-positive lesion were analyzed for the patients who underwent PET/MRI.ResultsA total of 178 biopsy cores were taken on the 55 patients. One hundred forty-six biopsy cores (82.0%, 146/178) from 51 (92.7%, 51/55) patients were positive for prostate cancer; 47 (85.5%, 47/55) were clinically significant prostate cancer. It is noteworthy that nine patients underwent both 18F-DCFPyL PET/CT and PET/MRI examinations; the seven patients with prostate cancer showed abnormal MR signal in the area of the PET-positive lesion while the other two patients with prostatic hyperplasia and prostatitis showed normal MR signal in the area of the PET-positive lesion.ConclusionThis study indicated that 18F-DCFPyL PET/CT-US or PET/MRI-US fusion targeted prostate biopsies may be valuable for prostate cancer diagnosis and have a high detection rate of clinically significant prostate cancer for PET-positive lesions. PET/MR can rule out some false PET-positive lesions, which may potentially reduce unnecessary prostate biopsies.

This paper researches the ascent trajectory optimization problem in view of multiple constraints that effect on the launch vehicle. First, a series of common constraints that effect on the ascent trajectory are formulated for the trajectory optimization problem. Then, in order to reduce the computational burden on the optimal solution, the restrictions on the angular momentum and the eccentricity of the target orbit are converted into constraints on the terminal altitude, velocity, and flight path angle. In this way, the requirement on accurate orbit insertion can be easily realized by solving a three-parameter optimization problem. Next, an improved particle swarm optimization algorithm is developed based on the Gaussian perturbation method to generate the optimal trajectory. Finally, the algorithm is verified by numerical simulation.

ObjectivesThe present study aims to compare the diagnostic efficacy of MR, 18F-FDG PET/CT, and 18F-FDG PET/MR for the local detection of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).Patients and MethodsThirty-six patients with histologically proven early-stage ENKTL were enrolled from a phase 2 study (Cohort A). Eight nasopharyngeal anatomical regions from each patient were imaged using 18F-FDG PET/CT and MR. A further nine patients were prospectively enrolled from a multicenter, phase 3 study; these patients underwent 18F-FDG PET/CT and PET/MR after a single 18F-FDG injection (Cohort B). Region-based sensitivity and specificity were calculated. The standardized uptake values (SUV) obtained from PET/CT and PET/MR were compared, and the relationship between the SUV and apparent diffusion coefficients (ADC) of PET/MR were analyzed.ResultsIn Cohort A, of the 288 anatomic regions, 86 demonstrated lymphoma involvement. All lesions were detected by 18F-FDG PET/CT, while only 70 were detected by MR. 18F-FDG PET/CT exhibited a higher sensitivity than MR (100% vs. 81.4%, χ2 = 17.641, P < 0.001) for local detection of malignancies. The specificity of 18F-FDG PET/CT and MR were 98.5 and 97.5%, respectively (χ2 = 0.510, P = 0.475). The accuracy of 18F-FDG PET/CT was 99.0% and the accuracy of MR was 92.7% (χ2 = 14.087, P < 0.001). In Cohort B, 72 anatomical regions were analyzed. PET/CT and PET/MR have a sensitivity of 100% and a specificity of 92.5%. The two methods were consistent (κ = 0.833, P < 0.001). There was a significant correlation between PET/MR SUVmax and PET/CT SUVmax (r = 0.711, P < 0.001), and SUVmean (r = 0.685, P < 0.001). No correlation was observed between the SUV and the ADC.ConclusionIn early-stage ENKTL, nasopharyngeal MR showed a lower sensitivity and a similar specificity when compared with 18F-FDG PET/CT. PET/MR showed similar performance compared with PET/CT.

A marine oil spill produces oil-related hazardous material (OHM) which can cause damage to the marine ecological environment, and seriously affect coastal economic development such as tourism and aquaculture. The turbulent momentum and energy generated by the wave breaking process have a significant effect on accelerating the mixing of OHM and seawater, which is one of the main factors in oil becoming sunken or submerged. In order to explore the influence of offshore wave breaking on the formation and transportation of OHM, the wave breaking process was simulated in a 2D laboratory flume, and the behavior process of OHM was identified and tracked in this paper. Five groups of breaking waves of different significant wave height (SWH) were set up in the experiment, and then OHM with the same density and mass was added, respectively, in order to observe the sinking process under the action of wave-induced turbulence. The results show that the turbulence intensity is closely related to the phase of the wave, the turbulence activity is violent at the wave crest, and the vertical distribution of the turbulent energy dissipation rate in the turbulent mixing zone remains basically unchanged. Under the actions of wave breaking and turbulence, the OHM’s submergence depth shows a good binomial growth trend. For SWH = 12.45 cm, the OHM stays under the water for nearly 2.32 s, and it reaches the deepest position of 0.165 m. Compared with SWH = 12.45 cm, the submergence depths for waves with SWHs of 20.61 cm, 26.81 cm, 32.32 cm, and 36.54 cm are increased by 8%, 37%, 80%, and 159%, respectively. Then, the submergence depths due to the other four waves are increased progressively, and the growth rates are 8%, 26%, 31%, 44%, respectively (compared with the same period of the previous wave).

The April 25, 2015 Mw7.8 Nepal earthquake was successfully recorded by Crustal Movement Observation Network of China (CMONOC) and Nepal Geodetic Array (NGA). We processed the high-rate GPS data (1 Hz and 5 Hz) by using relative kinematic positioning and derived dynamic ground motions caused by this large earthquake. The dynamic displacements time series clearly indicated the displacement amplitude of each station was related to the rupture directivity. The stations which located in the direction of rupture propagation had larger displacement amplitudes than others. Also dynamic ground displacement exceeding 5 cm was detected by the GPS station that was 2000 km away from the epicenter. Permanent coseismic displacements were resolved from the near-field high-rate GPS stations with wavelet decomposition-reconstruction method and P-wave arrivals were also detected with S transform method. The results of this study can be used for earthquake rupture process and Earthquake Early Warning studies.