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Background Brown-Vialetto-Van Laere syndrome-2 (BVVLS2) is a rare autosomal recessive neurological disorder caused by mutations in the SLC52A2 gene, which is characterized by early childhood onset of sensorineural hearing loss, bulbar palsy, peripheral neuropathy, and respiratory insufficiency. We aimed to investigate the genetic cause of a 4-year-old boy who suffered from BVVLS2 whose initial presentation was severe normocytic anemia and had been overlooked for three years in a local hospital. He was misdiagnosed with pure red cell aplasia (PRCA) and treated with hormones and chemotherapy drugs, but there was no obvious effect. Methods The targeted capture of 927 genes associated with neuromuscular disorders and next-generation sequencing were performed. Sanger sequencing was employed to verify the variant mutations. Results The proband was found to be heterozygous for c.350T > C (p.L117P) in exon 3 and c.1135_1137delTGG (p.W379del) in exon 5 of SLC52A2 gene. His anemia and neurological symptoms improved significantly after treatment with low dose oral riboflavin. Conclusions This study expands the mutational spectrum of SLC52A2 and phenotypic spectrum of BVVLS2, which provides a foundation for further investigations elucidating the SLC52A2 related mechanisms of BVVLS2. A low-dosage of riboflavin supplementation was used to obtain good curative effect, which provides further future references for the clinical treatments of BVVLS.

Deep learning has seen its promising applications in manufacturing processes. In this study, a deep network named Cascade Tri-DFPN based on the two-stage target detection algorithm is proposed for detecting the defects on the texture surface of plastic relays. The network adopts a derivative Resnet-101d as the backbone to obtain a loss-reduced feature extraction. Meanwhile, an enhanced feature pyramid module is put forward to enhance the feature representation of the network by adding a dense connection of feature layers through the self-attentive block. Moreover, the defect region proposals are optimized by introducing a cascade module to obtain high-quality defective proposal boxes. Experimental results on the augmented data set of relays’ surface defect reveal an average accuracy of 88.57% and an average recall rate of 94.58%, much higher than those of traditional RCNN or FPN detectors, demonstrating the remarkable improvement of the proposed network. Robustness of the method is also verified by performing tests with deteriorative image processing, which indicates an eligible defect detection under relatively complex scenarios such as image blurring. The proposed deep network could be used in surface defect detection of plastic relays and other potentially related industrial defect detection fields.

Even though high-strength steel has been widely used across the world, the global buckling behaviour of high-strength steel beams has yet to be systematically investigated through experimental tests and numerical simulations. This paper describes an experimental and numerical study of the lateral-torsional buckling resistance of welded Q690 steel beams. Eight beams with doubly-symmetric cross-sections and different height-to-width ratios were tested under a concentrated point load. To allow free lateral deflections, a special loading system was designed and erected at the mid-span of steel beams. The applied load remained in the vertical direction during the whole loading process, despite significant rotations and lateral deflections of the beam. The critical bending moment of steel beams was quantified in the experimental tests. Besides, numerical models were established by using ABAQUS and initial imperfections were properly defined in the model. Direct comparisons were made among numerical results of steel beams of different steel grades and design curves in different standards. Based on experimental and numerical results, recommendations were provided for the lateral-torsional buckling design of Q690 steel beams. It was suggested that GB50017-2003 and GB50017-201X can predict the buckling resistance of Q690 steel beams with slightly conservative results, Eurocode 3 yields rather conservative estimations, but ANSI/AISC360-10 significantly overestimates the buckling resistance.

Many field observations have shown that rock bursts occur frequently near the terminal mining line (TML) and dip coal pillar area in deep coalfaces. Taking the “7.26” rock burst in coalface 3302 in Xingcun Coal Mine as an example, the rock burst mechanism was investigated based on theoretical analysis and field observations, and a combined evaluation method using the stress field under seismic wave excitation was established to determine the reasonable TML of coalface 3302. Firstly, the static geological data revealed during roadway excavation were used for preevaluation of rock burst risk at the working face. By theoretically analyzing the stress transfer mechanism of the two types of the roof structure, the computational model of abutment pressure was established and the calculation method giving the abutment stress was proposed. Subsequently, a dynamic evaluation method that adopts microseismic and stress online monitoring system to monitor dynamic information, such as mine tremors and stress during coalface mining, was developed to define stress anomaly areas and then dynamically determine the TML. Finally, the proposed model was used to optimize the position of the TML of LW3302 in Xingcun Coal Mine; findings obtained in this study provide theoretical guidance for safe coal mining. Combined with the results of theoretical analysis (255 m), online stress monitoring (200 m), microseismic (MS) monitoring (262 m), and passive seismic velocity tomography (220–250 m), it can be finally determined that the width of the protective coal pillar for the TML of coalface 3302 should be at least 262 m.

Background Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. Extracellular volume (ECV) to guide late gadolinium enhancement (LGE) analysis may achieve a robust scar assessment. Methods Three cohorts of 80 non-ischemic-training, 20 non-ischemic-validation, and 10 ischemic-validation were prospectively enrolled and underwent 3.0 Tesla cardiac MRI. An ECV cutoff to differentiate LGE scar from non-scar was identified in the training cohort from the receiver-operating characteristic curve analysis, by comparing the ECV value against the visually-determined presence/absence of the LGE scar at the highest signal intensity (SI) area of the mid-left ventricle (LV) LGE. Based on the ECV cutoff, an LGE semi-automatic threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was optimized in the individual cases ensuring correspondence between LGE and ECV images. The inter-method agreement of scar amount in comparison with manual (for non-ischemic) or full-width half-maximum (FWHM, for ischemic) was assessed. Intra- and inter-observer reproducibility were investigated in a randomly chosen subset of 40 non-ischemic and 10 ischemic cases. Results The non-ischemic groups were all female with the HIV positive rate of 73.8% (training) and 80% (validation). The ischemic group was all male with reduced LV function. An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity: 86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). The identified n-SD threshold varied widely (range 3 SD–18 SD), and was independent of scar amount (β = −0.01, p = 0.92). In the non-ischemic cohorts, results suggested that the manual LGE assessment overestimated scar (%) in comparison to ECV-guided analysis [training: 4.5 (3.2–6.4) vs. 0.92 (0.1–2.1); validation: 2.5 (1.2–3.7) vs. 0.2 (0–1.6); P P Conclusions ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort. Trial registration ClinicalTrials.gov; NCT00000797, retrospectively-registered 2 November 1999; NCT02501811, registered 15 July 2015.

The success of neural network based methods in named entity recognition (NER) is heavily relied on abundant manual labeled data. However, these NER methods are unavailable when the data is fully-unlabeled in a new domain. To address the problem, we propose an unsupervised cross-domain model which leverages labeled data from source domain to predict entities in unlabeled target domain. To relieve the distribution divergence when transferring knowledge from source to target domain, we apply adversarial training. Furthermore, we design an entity-aware attention module to guide the adversarial training to reduce the discrepancy of entity features between different domains. Experimental results demonstrate that our model outperforms other methods and achieves state-of-the-art performance.

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.

Stimuli-responsive micro/nanostructures that exhibit not only programmable but also reprogrammable actuation behaviors are highly desirable for various advanced engineering applications (e.g., anticounterfeiting, information encoding, dynamic imaging and display, microrobotics, etc.) but yet to be realized with state-of-the-art technologies. Here we report a concept and a corresponding experimental technique for core-shell magnetic micropillars enabling simultaneously programmable and reprogrammable actuations using a simple magnetic field. The micropillars are composed of elastomeric hollow shells for shaping encapsulated with liquid magnetic nanocomposite resin cores for actuating. The spatial distribution of the magnetic nanoparticles inside the resin channels can be dynamically modulated within individual micropillars, which consequently regulates the magnetomechanical responses of the pillars upon actuation (bending deformation varied near 1 order of magnitude under the same actuation field). We demonstrate that the micropillars with contrasting bending responses can be configured in an arbitrary spatial pattern by direct magnetic writing, and the written pattern can then be easily magnetically erased to facilitate next-round rewriting and reconfiguration. This reprogrammable actuation capability of the micropillars is further demonstrated by their potential applications for rewritable paper and recyclable displays, where various microscale characteristics can be controlled to dynamically appear and disappear at the same or different locations of one single micropillar array. The core-shell magnetic micropillars reported here provide a universal prototype for reprogrammable responsive micro/nanostructures through rational design and facile fabrication from conventional materials.

Background: Odor identification dysfunction occurs early in Alzheimer’s disease (AD) and is considered a preclinical symptom along with subjective cognitive decline (SCD). Nevertheless, whether subjects with SCD are co-symptomatic with odor identification dysfunction remains unclear. Objective: To compare the degree of odor identification dysfunction and assess the relation between odor identification and cognitive performance in the AD spectrum (including SCD, mild cognitive impairment (MCI), and AD). Methods: Patients (84 SCD, 129 MCI, 52 AD) and 35 controls underwent the Sniffin’ Sticks Screen 16 test and comprehensive neuropsychological examination. Results: Odor identification scores were progressively lower moving from normal older adult to SCD, MCI, and AD. Additionally,the proportion of odor identification dysfunction were increasingly higher in the AD spectrum (p for trend

There were gender differences in the prevalence and severity of allergic diseases. Group 2 innate lymphoid cells (ILC2s) were recently reported to play a critical role in allergic diseases. We investigated the sex-dependent differences in ILC2-dominant allergic airway inflammation model using T\B cell-deficient mice, and determined the gender differences of ILC2 levels in patients with asthma and allergic rhinitis. Female mice exhibited higher levels of inflammatory infiltration and large production of IL-5 and IL-13, especially for ILC2 levels compared to male mice with the induction of IL-33. However, no significant differences were found for the levels of circulating ILC2s between the genders of patients. The treatment of testosterone significantly decreased the intracellular type 2 cytokines in ILC2s and the proliferation of pure ILC2s in response to epithelial cytokines. Our study suggested the sex differences and the involvement of androgen on ILC2s in allergic diseases.

Significance Anxiety disorders and obsessive-compulsive disorder (OCD) are highly prevalent and debilitating psychiatric disorders commonly co-occurring in our stressful modern life. Yet the common effective therapeutic target is still unknown. Here we report that activation of the histaminergic afferent system, particularly the histamine H3 receptor, in the nucleus accumbens (NAc) core, a vital node in the limbic loop, inhibits glutamatergic synaptic transmission in the circuit from the prelimbic prefrontal cortex (PrL) to NAc and improves both anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Our results define a common glutamatergic PrL–NAc circuit involved in both anxiety- and obsessive-compulsive-like behaviors modulated by the H3 presynaptic heteroreceptor and pave a path for developing potential strategies for clinical treatment of anxiety and OCD., Anxiety commonly co‐occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL– and not BLA– and vHipp–NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL–NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

Stable electron transport materials (ETMs) with fewer surface defects and proper energy level alignments with halide perovskite active layers are required for efficient perovskite solar cells (PSCs) with long-term durability. Here, two-dimensional van der Waals mixed valence tin oxides Sn2O3 and Sn3O4 are controllably synthesized and applied as ETMs for planar PSCs. The synthesized Sn2O3 and Sn3O4 have size of 5-20 nm and disperse well in water as stable colloids for months. Both Sn2O3 and Sn3O4 exhibit typical n-type semiconductor energy band structures, low trap density, and suitable energy level alignments with halide perovskites. Steady-state power conversion efficiencies (PCEs) of 22.36% and 21.83% are obtained for Sn2O3-based and Sn3O4-based planar PSCs. In addition, the half cells without hole transport materials and back electrodes show good UV-stability with average PCE of 99.0% and 95.7% for Sn2O3-based and Sn3O4-based devices remaining after 1000 h of ultraviolet soaking with an intensity of 70 mW cm-2.

Background With the increase of oral chemotherapy drugs, patients receiving cancer treatment prefer oral chemotherapy versus intravenous, given equal efficacy and toxicity. However, they need to take an active part in their care, which is vital with home-based oral therapy, therefore the self-management is important for patients with oral chemotherapy. Unfortunately, the development of self-management assessment tools for oral chemotherapy still lags behind. Methods The OCSMS item pool was formulated based on literature review and semi-structured interviews, An initial scale containing 5 dimensions and 38 items was constructed through research seminar, Delphi survey and pilot testing. To assess the validity and reliability, We recruited 261 patients from cancer hospital in China. Results A 36-item scale was developed with five dimensions identified through factor analysis: daily life management, symptom management, medication management, emotional cognitive management and social support. Cronbach’s coefficient Alpha, split-half coefficient, test-retest reliability and S-CVI/UA scores were 0.929, 0.773, 0.966 and 0.833, respectively, indicating that OCSMS has good reliability and validity. Conclusions The OCSMS is a valid, reliable measurement method of the self-management ability of patients with oral chemotherapy. The OCSMS shows potential as a tool to ensure the safety of patients with cancer. The OCSMS may help evaluate the effectiveness of interventions to improve the self-management ability of patients.

As one of the three most famous brewed wines in the world, Chinese rice wine is made from rice and husked millet, containing 14 percent to 20 percent alcohol. Highly original, yellow wine brewing techniques are regarded as the model of the wine brewing industry in Asia. Shaoxing Huangjiu is produced in Zhejiang province and remains the oldest and most representative Chinese rice wine. During storage, Shaoxing Huangjiu is susceptible to environmental disturbance and produces colloidal haze to result in turbidity. In this study, the main composition and source of colloidal haze protein in Shaoxing Huangjiu were analyzed by two‐dimensional electrophoresis and matrix‐assisted laser ionization time‐of‐flight tandem mass spectrometry (MALDI‐TOF/TOF MS). The results showed that the proteins in colloidal haze mainly consisted of oat protein b1, oat‐like protein, di‐amylase inhibitor, pathogenesis‐related protein, pathogenesis‐related protein‐4, chitinase II derived from wheat and oat‐like protein, and beta‐amylase derived from rice. The amino acid composition and secondary structure of haze protein and supernatant protein in Huangjiu were further explored by high‐performance liquid chromatography and Fourier transform infrared spectroscopy. The study has broadened knowledge of the main composition and source of colloidal haze protein in Shaoxing Huangjiu. The corresponding results indicated that the amino acid composition from colloidal haze had the main characteristics of high hydrophobicity and low water solubility., In this study, the main composition and source of colloidal haze protein in Chinese rice wine (Shaoxing Huangjiu) were analyzed by two‐dimensional electrophoresis and matrix‐assisted laser ionization time‐of‐flight tandem mass spectrometry (MALDI‐TOF/TOF MS). Meanwhile, the amino acid composition and secondary structure of haze protein and supernatant protein in Huangjiu were further explored by high‐performance liquid chromatography and Fourier transform infrared spectroscopy.

The possible mechanism of preeclampsia is investigated in this study to facilitate the exploration of the future remediation of this disease by analysing the changes of IL-17 and IL-35 in peripheral blood and placental tissue of pregnant women with preeclampsia (PE).The study was conducted using 45 healthy pregnant women as the control group and 90 pregnant women in the preeclampsia group, including 45 cases with severe preeclampsia and 45 cases with mild preeclampsia. All of 135 pregnant women underwent caesarean delivery. IL-17 and IL-35 concentrations in the serum were measured by ELISA, and IL-17 and IL-35 expression in placental specimens was detected by immunohistochemistry.There were no statistically significant differences in age among the three study groups. Serum IL-17 levels were significantly higher in PE patients than in healthy pregnant women (P 0.01). The ratio of positive staining for IL-17 was markedly higher in mild PE tissues (84.44%; 38/45) and severe PE tissues (86.67%; 39/45) than in healthy pregnant tissues (35.56%; 16/45) (P 0.01). The strong positive rates for IL-17 were markedly higher in mild PE tissues (48.89%; 22/45) and severe PE tissues (68.89%; 31/45) than in healthy pregnant tissues (13.33%; 6/45) (P 0.01). No differences between mild PE tissues and severe PE tissues were noted in both positive case rates and strong positive rates. Consistent with this finding, the ratio of strong positive staining for IL-35 was higher in healthy pregnant tissues (66.67%; 30/45) than in mild PE tissues (33.11%; 14/45) and severe PE tissues (26.67%; 12/45) (P 0.01).The abnormal increase in serum and placental of IL-17 has an association with the formation and development of PE. IL-35 expression is significantly lower in severe PE placenta tissue and serum compared with normal pregnant women. These results suggested that IL-17/IL-35 imbalance may play a role in the pathophysiology of PE.

Background: Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival. Methods: We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss. Results: Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P= 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305–7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio= 0.359; 95% CI= 0.197–0.652; P= 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130–0.728; P = 0.007) with ECD kidneys. Conclusion: DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys. Key words: Chronic kidney disease; Delayed graft function; Expanded-criteria donors; Graft survival; Standard-criteria donors

Purpose To investigate a method to classify tissues types for synthetic CT generation using MRI for treatment planning in abdominal radiotherapy. Methods An institutional review board approved volunteer study was performed on a 3T MRI scanner. In‐phase, fat and water images were acquired for five volunteers with breath‐hold using an mDixon pulse sequence. A method to classify different tissue types for synthetic CT generation in the abdomen was developed. Three tissue clusters (fat, high‐density tissue, and spine/air/lungs) were generated using a fuzzy‐c means clustering algorithm. The third cluster was further segmented into three sub‐clusters that represented spine, air, and lungs. Therefore, five segments were automatically generated. To evaluate segmentation accuracy using the method, the five segments were manually contoured on MRI images as the ground truth, and the volume ratio, Dice coefficient, and Hausdorff distance metric were calculated. The dosimetric effect of segmentation accuracy was evaluated on simulated targets close to air, lungs, and spine using a two‐arc volumetric modulated arc therapy (VMAT) technique. Results The volume ratio of auto‐segmentation to manual segmentation was 0.88–2.1 for the air segment and 0.72–1.13 for the remaining segments. The range of the Dice coefficient was 0.24–0.83, 0.84–0.93, 0.94–0.98, 0.93–0.96, and 0.76–0.79 for air, fat, lungs, high‐density tissue, and spine, respectively. The range of the mean Hausdorff distance was 3–29.1 mm, 0.5–1.3 mm, 0.4–1 mm, 0.7–1.6 mm, and 1.2–1.4 mm for air, fat, lungs, high‐density tissue, and spine, respectively. Despite worse segmentation accuracy in air and spine, the dosimetric effect was 0.2% ± 0.2%, with a maximum difference of 0.8% for all target locations. Conclusion A method to generate synthetic CT in the abdomen was developed, and segmentation accuracy and its dosimetric effect were evaluated. Our results demonstrate the potential of using MRI alone for treatment planning in the abdomen.

Phase aberration is one of the prime factors that degrade the quality of observed images. Pupil-size diversity technology (PSDT) is a newly developed post-processing method for aberration correction and image reconstruction. However, images reconstructed using PSDT suffer from massive grains when imaging astronomical faint objects, which extremely limits its further application. In this paper, we propose an improved PSDT with embedded denoising reprocessing to overcome this drawback. Diversity raw images, generated by modulating the size of the pupil, are firstly processed by blocking-matching and 3D filtering (BM3D), a state-of-art denoising algorithm. Then, the traditional PSDT can be employed to estimate the wavefront and reconstruct a high-resolution image. Both numerical simulations and experiment demonstrations show that our proposed strategy exhibits superior performance for aberrations correction and image restoration of faint objects in view of its efficiency and robustness. Being capable of realizing high-resolution imaging with faint objects, this proposed method may have important application prospects in the fields of astronomical object detection, remote sensing, etc.

Background: Neuropsychiatric symptoms (NPS) and cognitive impairments are both common in patients with late-life depression (LLD). However, the relationship between NPS and cognitive functions in LLD patients remains unclear. The current study aims to explore the effects of NPS on cognitive impairments in LLD patients.Methods: Two hundred and sixty-two LLD patients and 141 normal controls (NC) were recruited. Exploratory factor analysis was used to extract factors from the Neuropsychiatric Inventory (NPI). Correlation, mediation, and moderation analyses were used to explore whether NPS exacerbated the cognitive impairments in LLD and whether NPS exhibited different effects on cognitive impairments in acute-state LLD (aLLD) and recovery-state LLD (rLLD).Results: Three main factors were extracted from the NPI, including emotional, behavioral, and psychotic factors. The patients with LLD exhibited worse cognition and higher NPI scores, and the scores of NPI-total and three extracted factors were negatively associated with cognitive scores. The mediation analyses exhibited that NPI-total and behavioral factor scores increase the difference in cognition scores between LLD and NC groups. The mediation analyses exhibited that behavioral factor score played a greater effect on impairing MMSE in the rLLD group than in the aLLD group. Additionally, behavioral factor score was in a trend to be negatively associated with Mini-Mental State Examination (MMSE) score changes at a one-year follow-up (p = 0.051).Conclusions: NPS, especially behavioral symptoms, exacerbate cognitive impairments in LLD and may contribute to residual cognitive impairment in rLLD patients. Early intervention for behavioral symptoms in LLD patients may be beneficial to their long-term clinical prognosis.

To remove space debris actively, the key step is choosing a suitable capturing method. The size characteristics of space debris are an important factor that affects the capturing method. This paper presents a contour-extracting algorithm for rolling targets, such as space debris. The representation of the point in Euclidean space is converted to a conformal space to obtain candidate contour points through the computational geometric and topological relationships among the points, lines, and surfaces in a high-dimensional space. By combining this conversion with the multiview stitching algorithm, the complete candidate contour point model is obtained. The final contour points are extracted by determining the concave and convex points in conformal space. Simulation results prove that the unified expression of the geometric features in conformal space not only reduces the computational complexity but also increases the speed of the contour point extraction. The method proposed in this paper is superior to other methods in terms of measurement accuracy, speed, and robustness; in particular, the accuracy increased by 60%.

Striving to develop public transport is an effective way of alleviating traffic congestion in large and medium-sized cities, and arterial transit signal priority is an important measure for improving the reliability of bus operations. However, only few studies have evaluated the quality of arterial transit signal priority scenarios. To address this gap this article proposes a transit signal priority scheme evaluation model. First, an evaluation index for arterial transit signal priority is established. Second, a decisive model of interval D-S evidence theory for arterial transit signal priority is built. Finally, to address the uncertainty of the index attribute and the one-sidedness of a single decision maker, the advantages and disadvantages of the model is assessed on the basis of D-S evidence theory, and the optimal scheme is selected. This research provides a new theory and method for the transit signal priority scheme that can effectively avoid the one-sidedness of a single decision maker in evaluating transit signal priority and the uncertainty of index attributes, and provides technical support for extending the application of transit signal priority.

The knowledge of bubble profiles in gas-liquid two-phase flows is crucial for analyzing the kinetic processes such as heat and mass transfer, and this knowledge is contained in field data obtained by surface-resolved computational fluid dynamics (CFD) simulations. To obtain this information, an efficient bubble profile reconstruction method based on an improved agglomerative hierarchical clustering (AHC) algorithm is proposed in this paper. The reconstruction method is featured by the implementations of a binary space division preprocessing, which aims to reduce the computational complexity, an adaptive linkage criterion, which guarantees the applicability of the AHC algorithm when dealing with datasets involving either non-uniform or distorted grids, and a stepwise execution strategy, which enables the separation of attached bubbles. To illustrate and verify this method, it was applied to dealing with 3 datasets, 2 of them with pre-specified spherical bubbles and the other obtained by a surface-resolved CFD simulation. Application results indicate that the proposed method is effective even when the data include some non-uniform and distortion.

Natural disaster vulnerability can intuitively reflect the susceptibility of an area to environmental changes. Better understanding the spatial distribution of natural disaster vulnerability is a critical process for taking effective adaptation and management. Although significant achievements have been made in disaster vulnerability, few studies are known about natural disaster vulnerability at the national scale, especially from the typical natural disaster events in China. In this study, with normalizing selected indicators and calculating vulnerability index, we analyzed the spatial distribution of natural disasters vulnerability during 2010–2017 using the geospatial techniques. The results showed that natural disaster vulnerability has certain spatial differences, but different natural disaster can occur in the same area during the study period. Drought disaster can occur in all regions of China, especially in Inner Mongolia. Flood disaster is mainly concentrated in the middle and lower reaches of the Yangtze River and the Yellow River Basin. The wind and storm disaster is chiefly in the northern regions in China. The freezing disaster is widely distributed in China. Furthermore, the regions with low vulnerability were primarily distributed in the eastern coastal region, indicating that the rapid development of economy and technology can resist or mitigate natural disaster to a certain extent. This study offers a solution to study natural disasters and provides scientific basis for disaster prevention and mitigation actions.

The fatigue life prediction of solder joints under random vibration load is one of the most important aspect in design of packaging. A fatigue-life estimation in the frequency domain is proved to have advantages in comparison to the time-domain estimation. This paper presents a comparison of the fatigue life prediction of solder joints under random vibration load by several popular frequency domain methods, including the narrow-band, the Wirsching–Light, the single-moment, the Empirical α0.75, the Tovo–Benasciutti, the Zhao–Baker, and the Dirlik methods. The comparison between these selected frequency domain methods and the traditional Steinberg method was investigated with the help of the relative error. Results indicate that most spectral methods are accurate than the Steinberg method, the Tovo–Benasciutti method is proved to be the best method for the life estimation of solder joints suited not only to the BGA package but also to the PoP package.

Objectives:Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression.Methods:A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE.Results:Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores.Conclusions:This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.

The diversity of immune responses in allergic diseases is critically mediated by dendritic cells (DCs), including myeloid and plasmacytoid DCs. Allergen inhalation increased the release of IL-33 from patients with allergic rhinitis (AR), which affecting the downstream cells by binding to its receptor (ST2). However, the effects of inhaled allergens on the expression of ST2 by DCs and IL-33 on the function of mDCs are unknown. The levels of ST2+mDCs and ST2+pDCs in the blood from patients with AR and healthy subjects were examined using flow cytometry. Moreover, the patients were challenged using the allergens and the levels of ST2+mDCs and ST2+pDCs were investigated at different time points. We found that there were higher levels of ST2+ mDCs and ST2+ pDCs in patients with AR, and these levels were further increased 0.5 h after allergen inhalation. Additionally, the type 2 immune response was upregulated after challenge. IL-33 treatment increased the expression of ST2 on mDCs. Our study demonstrated that ST2 was upregulated on DCs after allergen inhalation and that mDCs responded directly to IL-33 through ST2, suggesting that the IL-33/ST2 axis might play an important role in the pathogenesis of allergic rhinitis by DCs.

Allergic diseases include asthma, atopic-dermatitis, allergic-rhinitis, drug hypersensitivity and food-allergy. During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical-burden. A large fraction of allergic diseases is characterized by a type-2 immune response involving Th2 cells, type-2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and non-invasive methods. In recent years, a plethora of research has been directed towards finding novel biomarkers of allergic diseases. Promising biomarkers of type-2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric-oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body-fluids and exhaled-air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic-urticaria, atopic-dermatitis, allergic-rhinitis, chronic-rhinosinusitis, food-allergies, anaphylaxis, drug hypersensitivity and allergen-immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.

Three-dimensional (3D) printing technologies have been increasingly utilized in medicine over the past several years and can greatly facilitate surgical planning thereby improving patient outcomes. Although still much less utilized compared to computed tomography (CT), magnetic resonance imaging (MRI) is gaining traction in medical 3D printing. The purpose of this study was two-fold: 1) to determine the prevalence in the existing literature of using MRI to create 3D printed anatomic models for surgical planning and 2) to provide image acquisition recommendations for appropriate clinical scenarios where MRI is the most suitable imaging modality. The workflow for creating 3D printed anatomic models from medical imaging data is complex and involves image segmentation of the regions of interest and conversion of that data into 3D surface meshes, which are compatible with printing technologies. CT is most commonly used to create 3D printed anatomic models due to the high image quality and relative ease of performing image segmentation from CT data. As compared to CT datasets, 3D printing using MRI data offers advantages since it provides exquisite soft tissue contrast needed for accurate organ segmentation and it does not expose patients to unnecessary ionizing radiation. MRI, however, often requires complicated imaging techniques and time-consuming postprocessing procedures to generate high-resolution 3D anatomic models needed for 3D printing. Despite these challenges, 3D modeling and printing from MRI data holds great clinical promises thanks to emerging innovations in both advanced MRI imaging and postprocessing techniques. EVIDENCE LEVEL: 2 TECHNICAL EFFICATCY: 5.

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. Results: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. Conclusions: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.

This paper investigates the influences of change recipients’ supportive behaviors toward the national reform in the Chinese football sector. Qualitative data were collected through semi-structured interviews (n = 29), which were conducted with change recipients from national and local football associations and commercial football clubs. Drawing on an integrated conceptual framework, the findings suggest that the change-supportive behaviors demonstrated by the change recipients were influenced and incentivised by managerial factors (i.e., management competency, communication channels, participation in decision-making, leaders’ commitment to change, and principal support); and contextual factors (i.e., an amenable football environment and the perceived political pressure to change). Three manifestations of change-supportive behaviors were identified: a) showing understanding of the change but pessimistic about the outcome; b) supporting the change and being willing to take risks; and c) supporting the change and actively seeking alternative solutions.

Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis.Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants.Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (Pauc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (Pauc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, Pfdr = 0.0744 & P = 0.0004, Pfdr = 0.0744).Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD.

Robot detection, recognition, positioning, and other applications require not only real-time video image information but also the distance from the target to the camera, that is, depth information. This paper proposes a method to automatically generate any monocular camera depth map based on RealSense camera data. By using this method, any current single-camera detection system can be upgraded online. Without changing the original system, the depth information of the original monocular camera can be obtained simply, and the transition from 2D detection to 3D detection can be realized. In order to verify the effectiveness of the proposed method, a hardware system was constructed using the Micro-vision RS-A14K-GC8 industrial camera and the Intel RealSense D415 depth camera, and the depth map fitting algorithm proposed in this paper was used to test the system. The results show that, except for a few depth-missing areas, the results of other areas with depth are still good, which can basically describe the distance difference between the target and the camera. In addition, in order to verify the scalability of the method, a new hardware system was constructed with different cameras, and images were collected in a complex farmland environment. The generated depth map was good, which could basically describe the distance difference between the target and the camera.

Pulmonary infection is common in patients with heart failure, yet the risk factors remain unclear. We aimed to evaluate the clinical characteristics and risk factors of pulmonary infection in elderly patients with heart failure, to provide reference to the prevention of pulmonary infection.This study was a retrospective study design. We included elderly heart failure patient admitted to our hospital from April 1, 2018 to August 31, 2020. The characteristics and clinical data of pulmonary infection and no infection patients were assessed. Logistic regression analyses were conducted to identify the risk factors of pulmonary infections in patients with heart failure.A total of 201 patients were included. The incidence of pulmonary infection in patients with heart failure was 23.88%. There were significant differences in the age, diabetes, New York Heart Association (NYHA) grade, left ventricular ejection fraction (LVEF), C-reactive protein (CRP) between infection and no infection group (all P .05), and there were not differences in the sex, body mass index, alcohol drinking, smoking, hypertension, hyperlipidemia, length of hospital stay between 2 groups (all P .05). Logistic regression analyses indicated that age ≥70 years, diabetes, NYHA grade III, LVEF ≤55%, and CRP ≥10 mg/L were the independent risk factors of pulmonary infections in patients with heart failure (all P .05). Pseudomonas aeruginosa (34.48%), Staphylococcus aureus (19.57%), and Klebsiella pneumoniae (15.22%) were the most common 3 pathogens in patients with pulmonary infection.Heart failure patients with age ≥70 years, diabetes, NYHA grade III, LVEF ≤55%, and CRP ≥10 mg/L have higher risks of pulmonary infections, preventive measures targeted on those risk factors are needed to reduce pulmonary infections.

Background: Potential modification of the association between maternal particulate matter (PM) exposure and preterm delivery (PTD) by folic acid (FA) supplementation has not been studied. Objective: We examined whether FA supplementation could reduce the risk of PTD associated with maternal exposure to PM in ambient air during pregnancy. Method: In a cohort study covering 30 of the 31 provinces of mainland China in 2014, 1,229,556 primiparas of Han ethnicity were followed until labor. We collected information on their FA supplementation and pregnancy outcomes and estimated each participant’s exposure to PM with diameters of ≤10μm (PM10), 2.5μm (PM2.5), and 1μm (PM1) using satellite remote-sensing based models. Cox proportional hazard regression models were used to examine interactions between FA supplementation and PM exposures, after controlling for individual characteristics. Results: Participants who initiated FA ≥3 months prior to pregnancy (38.1%) had a 23% [hazard ratio (HR)=0.77 (95% CI: 0.76, 0.78)] lower risk of PTD than women who did not use preconception FA. Participants with PM concentrations in the highest quartile had a higher risk of PTD [HR=1.29 (95% CI: 1.26, 1.32) for PM1, 1.52 (95% CI: 1.46, 1.58) for PM2.5, and 1.22 (95% CI: 1.17, 1.27) for PM10] than those with exposures in the lowest PM quartiles. Estimated associations with a 10-μg/m3 increase in PM1 and PM2.5 were significantly lower among women who initiated FA ≥3 months prior to pregnancy [HR=1.09 (95% CI: 1.08, 1.10) for both exposures] than among women who did not use preconception FA [HR=1.12 (95% CI: 1.11, 1.13) for both exposures; pinteraction

This paper starts with a brief introduction of computer-aided product innovation design technology, and then expounds the application of computer-aided product design technology in computer-aided innovation in detail. Then it expounds the hardware design of computer-aided product innovation system; Then it analyzes the application of knowledge resources in the process of computer-aided product innovation design, including the comprehensive utilization of knowledge resources in computer-aided product innovation design and the obstacles to the application of knowledge resources in computer-aided product innovation design. This paper starts with a brief introduction of computer-aided product innovation design technology, and then expounds the application of computer-aided product design technology in computer-aided innovation in detail. Then it analyzes the application of knowledge resources in the process of computer-aided product innovation design, including the comprehensive utilization of knowledge resources in computer-aided product innovation design and the obstacles to the application of knowledge resources in computer-aided product innovation design. Finally, the paper analyzes the product innovation design based on computer-aided innovation technology, including the problems in the process of product innovation design, how to solve the problems encountered in the process of product design, the generation of solutions to the problems in the process of product design and the process of value analysis in product innovation design, in order to make product design stakeholders pay attention to the research and specific research and development process of computer-aided product innovation design system.

In order to evaluate the maximum available wind power capacity more accurately, a comprehensive evaluation method based on peak load regulation capability, static security and transient stability is proposed. With the help of stochastic production simulation technology, the wind power capacity absorbed by the power grid under the constraint of traditional peak load regulation capacity is modified, the combined capacity of each wind power access point is globally optimized by enumeration method, and the transient stability of the system is verified by setting large disturbance conditions, and finally the maximum wind power capacity that can be absorbed by the regional power grid is obtained.

A control design approach with the integration of online delay estimation is proposed for wireless networked control systems (WNCSs) with unknown round-trip delay, which improves control performance in a practically feasible way. We introduce a delay probability estimation unit to obtain the delay characteristics by estimating the delay when the control system is running. We also present a piecewise approximation control strategy to take advantage of the estimation. Furthermore, the control gain is synthesized with stability guarantee. The conditions to ensure the stochastic stability of the closed-loop system are given, and the effectiveness of the proposed approach is verified numerically.

so-called MGMN (Multiple-Granularity- Middle Network) algorithm is proposed to improve the detection accuracy of distracted driving, based on multigranularity features and middle-level features. The algorithm is derived from the ResNet50 neural network and is the first time to use multi-granularity features and mid-level features of images in the field of distracted driving detection. The multigranularity feature extraction module consists of three branches: the global branch to learn the global features without local information, the second branch to divide the image level into two parts and later to learn the local features of the upper and lower parts, and the third branch to divide the image level into three parts, and later to learn the local features of the upper, middle and lower parts. By extracting the features of the middle layer of the image, the feature extraction of the algorithm is enriched. While the multi-granularity features are individually input to the cross-entropy loss function, the multi-granularity features of the image and the middle-level features are combined and input into the cross-entropy loss function. The proposed algorithm has an accuracy of 99.8% on the dataset "Districted-Driver- Detection" published by State Farm Company, which is 1.5% to 3% higher than existing algorithms, and an improved accuracy of 98.7% on the dataset "AUC-Districted-Driver-Detection".

IntroductionThis study aimed to investigate the preventive effects of oral administration of probiotics on the incidence and severity of atopic dermatitis (AD) in infants.Material and methodsA total of 396 full-term infants were enrolled in this study. Of these, 132 newborns without a family history of AD were assigned to group A, and the other 264 newborns were randomly divided into groups B and C. Infants in groups A and B were solely breastfed, while probiotics were administered to those in group C as well as breastfeeding. The information of all subjects was recorded, and the incidence of AD was followed up. The levels of serum IgE and IL-4 were measured at the age of 3 years.ResultsThe incidence of AD in infants in group B was higher than that in group A at 3 months, 4–6 months, and 7–36 months after birth, together with increased symptom scores. For infants in group C, the incidence of AD at 4–6 months and 7–36 months after birth and the SCORAD scores at 0–3 months and 4–6 months after birth were lower than those in group B. The levels of IgE and IL-4 in group B were higher than those in groups A and C at 36 months old.ConclusionsAdding probiotics could favor the establishment of the intestinal microecological balance in the neonatal period, thereby reducing the incidence of AD, decreasing the levels of serum immune indexes and alleviating the severity of the disease.

Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

Esports is a rapidly growing industry. However, the unidentifiable governance structure of the industry has contributed to a number of integrity-eroding activities. By exploring esports stakeholder dynamics, this paper answers the question, &ldquo, Is the esports governance model sustainable?&rdquo, Data were sourced from documentation, focus groups (N = 3) and semi-structured interviews (N = 6). Thematic analysis was conducted using Nvivo. The findings suggest that (1) the current esports governance framework features some attributes of the &ldquo, lead organisation-governed network&rdquo, with the power residing mainly in game publishers, (2) the rising power of other stakeholders in the network seeking to address integrity issues has caused fragmentation of the esports governance framework, (3) esports governance is evolving towards a network administration organisation (NAO) model. Such evolution has a few challenges&mdash, most notably, the compliance of game publishers. Given the social impact of the integrity issues, governments should play a main role in facilitating a NAO model.

Background Our previous study in animal models revealed that bilirubin could induce Aβ formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aβ deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain-barrier may benefit the treatment of Alzheimer's disease (AD). Objectives The objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aβ deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD. Methods Bilirubin and albumin concentrations in dementia patients with Aβ deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms. Results Significantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies, and general paresis of insane. In vitro assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores. Conclusion IBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aβ deposition, and intravenous administration of albumin is beneficial to AD treatment. Trial registration The intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.

Background Thalassemia is a common inherited hematological disease in tropical and subtropical regions. This study aimed to investigate the mutation spectrum of thalassemia in the Dongguan region of southern China and comprehensively analyze hematologic features of thalassemia carriers with various types of globin mutations. Methods A hematological screening including hematological indices such as mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH), and mean corpuscular hemoglobin concentration (MCHC) was conducted in 19 442 people from Dongguan region, Guangdong province of China. Then, 4891 suspected thalassemia carriers were further investigated by genetic analysis of combined NGS and gap‐PCR. Results Totally, 2319 (11.9%) cases were diagnosed as carriers of thalassemia, of which 1483 cases (7.6%) were α‐thalassemia, 741 cases (3.8%) were β‐thalassemia, and 95 cases (0.5%) were co‐inheritance of α‐ and β‐thalassemia. In α‐thalassemia carriers, the phenotypic severity increases with the number of nonfunctional α‐globin genes. The patients with –SEA/αWSα genotype have less severe clinical phenotypes than those with other Hb H diseases. As for β‐thalassemia, the MCV and MCH in both β0 and β+ carriers are markedly reduced. Conclusions This is the first comprehensive molecular epidemiological survey and hematological profiling of thalassemia in Dongguan area. This study will be benefit for genetic counseling in the clinic and may help pediatricians to make a correct diagnosis of different types of thalassemia., This study is the first large‐scale epidemiological investigation and full‐spectrum analysis of mutations and hematological profile in thalassemia in Dongguan, southern China. The results of this study will provide reference for genetic counseling and preventive measures to reduce cases of the severe thalassemia. In addition, the genotype‐phenotype correlation in this study might help the clinicians to have rapid and accurate referrals in genetic counseling.

Background: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer’s disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. Objective: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Methods: Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1–40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Results: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. Conclusion: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

Effectively monitoring ships and discovering abnormal ship trajectory in time is necessary for marine traffic supervision. The basic work of discovering the ship’s abnormal trajectory is to predict the ship’s navigation dynamically. Previous works in ship trajectory prediction are basically concern on single-source data, for example, the AIS data. These methods ignore the relations between different sources which may improve the performance of predicting ship trajectory. We propose a neural sequence model based on heterogeneous multisource fusion for ship trajectory completion and prediction. Our method makes better utilization of AIS, GPS and ARPA radar information to predict ship trajectory precisely. We construct a dataset which contains about 8 million ship trajectory samples and the experiments demonstrate that our multi-source fusion model gains promising results.

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia.