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Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4‐related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4‐mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain‐of‐function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT‐mediated α‐synuclein (α‐syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α‐syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT‐induced α‐syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α‐syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4‐related disorders and related therapeutic strategies. [ABSTRACT FROM AUTHOR]

Currently, the discriminative correlation filter‐based trackers have achieved higher tracking accuracy. However, visual tracking still faces challenges in terms of heavy occlusion, scale variation and so on. In this study, the authors intend to solve heavy occlusion by introducing collaborative model into classifier‐box. Firstly, they introduce complex colour features into correlation filter tracker to improve the effect of the tracker. Secondly, they introduce a multi‐scale method into their tracker to ease the scale problem. Thirdly, in order to solve the heavy occlusion in the tracking process, they adopt the locally weighted distance and classifier‐box. Their algorithm achieves distance precision rates of 81.7 and 77.4% on OTB2013 dataset and OTB2015 dataset, respectively. Their contribution focuses on solving heavy occlusion by using colour features, locally weighted distance and classifier‐box. The experimental results on OTB2013 and OTB2015 datasets demonstrate their algorithm to perform better than state‐of‐the‐art methods. [ABSTRACT FROM AUTHOR]

Discriminative correlation filter‐based tracking algorithms have recently shown impressive performance on benchmark data sets. However, visual tracking is still a challenging task in the case of partial occlusions, irregular deformations and so on. In this study, the authors intend to solve these issues by introducing the adaptive collaborative model into part‐based tracking. First, instead of a simple linear superposition, the collaborative strategy they proposed combines the template model and colour‐based model adaptively and relies on the strengths of both to promote the accuracy. Second, we utilise the voting strategy to figure out the final object position from reliable parts, and the motion information is used in evaluation for reliable parts to enable the tracker to be robust in various situations. Third, the authors utilise a discriminative multi‐scale estimate method to solve the problem of scale variations. Finally, they introduce a dimensionality reduction method to limit the computational complexity of the tracker. Abundant experiments demonstrate that the tracker performs superiorly against several advanced algorithms on both the Online Tracking Benchmark (OTB) 2013 and OTB2015 data sets while maintaining the high frame rates. [ABSTRACT FROM AUTHOR]

Resumen A partir de una muestra de recién graduados del área de Beijing, se examinan cómo afectan a las perspectivas de empleo y a los salarios iniciales el prestigio de la universidad (como ≪señal≫ de competencia y calificación), la especialidad y el sexo. Las estimaciones con un modelo paramétrico de supervivencia y un modelo de selección de Heckman muestran que los graduados de universidades prestigiosas encuentran trabajo más rápidamente y reciben salarios iniciales más altos que los de otras universidades, así como los graduados en ingeniería y empresariales, mientras que los de humanidades y ciencias sociales obtienen salarios iniciales más altos. Las mujeres encuentran trabajo más rápido, pero ganan menos que los hombres. [ABSTRACT FROM AUTHOR]

Aims The Notch signalling pathway is involved in normal development as well as tumorigenesis. However, it is unclear whether Notch activation is related to diverse clinicopathological factors in papillary thyroid carcinoma ( PTC). Methods and results We examined the relationship between clinicopathological factors and the expression of activated Notch1 and Hey1, which are indicators of Notch signalling pathway activation, in 109 PTC cases. Activated Notch1 showed strong, moderate and weak expression in 23, 48 and 36 cases, respectively. Its expression was related significantly to histopathological variants ( P = 0.007), lymph node metastasis ( P = 0.016), BRAF mutation ( P = 0.036) and extent of surgery ( P = 0.014). Hey1 immunostaining could be divided into two groups: positive and negative, with 26 and 83 cases, respectively. Its expression was related significantly to histopathological variants ( P = 0.026), extrathyroidal extension ( P = 0.005), BRAF mutation ( P = 0.048) and recurrence or soft tissue metastasis ( P = 0.000). Multivariate analysis revealed that tumour size (>1 cm), Hey1 immunoreactivity and the presence of lymph node metastasis were associated significantly with recurrence or soft tissue metastasis (odds ratio = 7.38, 4.28 and 12.00, respectively). Conclusions Thus, we found that activation of Notch signalling was correlated significantly with clinicopathological parameters. Therefore, Notch signalling could be a useful prognostic marker in patients with PTC. [ABSTRACT FROM AUTHOR]

Recently, Siamese‐based trackers have drawn amounts of attention in visual tracking field because of their excellent performance on different tracking benchmarks. However, most Siamese‐based trackers encounter difficulties under circumstances such as similar objects interference and background clutters. Besides, there exists an extreme foreground–background data imbalance that weakens the performance during training but few loss functions pay attention to it. The authors intend to address the issues mentioned above by introducing a module named paralleled spatial and channel attention (PSCA) and adaptive focal loss (AFL). Firstly, paralleled spatial and channel attention is proposed to enhance the extracted features and eliminate the noise information from both spatial and channel aspects. Secondly, adaptive focal loss is proposed as the loss function to make the model focus on hard samples that contribute more to training process. Finally, paralleled spatial and channel attention and modified ResNet are combined for extracting more powerful features. Experimental results show that the authors' method achieves outstanding performance in multiple benchmarks while keeping a beyond‐real‐time frame rate. [ABSTRACT FROM AUTHOR]

Recently, kernelised correlation filter (KCF)‐based trackers aroused increasing interest and achieved extremely compelling results in different competitions and benchmarks in the field of visual object tracking. However, the training mechanism of the KCF that exploits simple linear combinations of filter from the previous frame easily cause error accumulation. To overcome this problem, the authors propose a novel training strategy that utilises all of the previous training samples, and a sparsity‐related loss function regularised by the L1 norm to deal with the problem of the fixed template size in KCF trackers, a separate scale filter is learned for scale estimation during the tracking process. Moreover, powerful features that include histogram of oriented gradients (HOG) and colour features are integrated to further improve the robustness of the authors' tracking. Extensive experiments in various challenging situations demonstrate that the proposed method performs favourably against several state‐of‐the‐art tracking algorithms. [ABSTRACT FROM AUTHOR]

Introduction: AML patients with KMT2A‐MLLT3 and other 11q23 abnormalities belong to the intermediate and high‐risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site‐1 (EVI1) overexpression suits either the subtypes of KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. Methods: We retrospectively analyzed the clinical characteristics of 166 KMT2A‐r and KMT2A‐PTD AML patients. Results: For the Non‐KMT2A‐MLLT3 group, patients in the EVI1‐high subgroup had shorter OS and DFS and higher CIR than those in the EVI1‐low subgroup (p =.027, p =.018, and p =.020, respectively). Additionally, both KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo‐HSCT) regardless of their EVI1 expression level (all p <.001). For transplanted patients with KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 rearrangement, the EVI1‐high subgroup had worse prognosis than the EVI1‐low subgroup (all p <.05). The 2‐year CIR of the KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2‐year CIR of transplanted patients with KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 was relatively low. Conclusions: Our study showed that for the Non‐KMT2A‐MLLT3 group, the EVI1‐high group had shorter OS and DFS than the EVI1‐low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1‐high patients with non‐KMT2A‐MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration. [ABSTRACT FROM AUTHOR]

The article presents chemical equations for the article "Copper-Mediated Trifluoromethylation of Propargyl Acetates Leading to Trifluoromethyl-allenes" by J.-J. Kong and others published in the journal "Organic & Biomolecular Chemistry" in 2014.

Purpose: Accurately segmenting curvilinear structures, for example, retinal blood vessels or nerve fibers, in the medical image is essential to the clinical diagnosis of many diseases. Recently, deep learning has become a popular technology to deal with the image segmentation task, and it has obtained remarkable achievement. However, the existing methods still have many problems when segmenting the curvilinear structures in medical images, such as losing the details of curvilinear structures, producing many false‐positive segmentation results. To mitigate these problems, we propose a novel end‐to‐end curvilinear structure segmentation network called Curv‐Net. Methods: Curv‐Net is an effective encoder–decoder architecture constructed based on selective kernel (SK) and multibidirectional convolutional LSTM (multi‐Bi‐ConvLSTM). To be specific, we first employ the SK module in the convolutional layer to adaptively extract the multi‐scale features of the input image, and then we design a multi‐Bi‐ConvLSTM as the skip concatenation to fuse the information learned in the same stage and propagate the feature information from the deep stages to the shallow stages, which can enable the feature captured by Curv‐Net to contain more detail information and high‐level semantic information simultaneously to improve the segmentation performance. Results: The effectiveness and reliability of our proposed Curv‐Net are verified on three public datasets: two color fundus datasets (DRIVE and CHASE_DB1) and one corneal nerve fiber dataset (CCM‐2). We calculate the accuracy (ACC), sensitivity (SE), specificity (SP), Dice similarity coefficient (Dice), and area under the receiver (AUC) for the DRIVE and CHASE_DB1 datasets. The ACC, SE, SP, Dice, and AUC of the DRIVE dataset are 0.9629, 0.8175, 0.9858, 0.8352, and 0.9810, respectively. For the CHASE_DB1 dataset, the values are 0.9810, 0.8564, 0.9899, 0.8143, and 0.9832, respectively. To validate the corneal nerve fiber segmentation performance of the proposed Curv‐Net, we test it on the CCM‐2 dataset and calculate Dice, SE, and false discovery rate (FDR) metrics. The Dice, SE, and FDR achieved by Curv‐Net are 0.8114 ± 0.0062, 0.8903 ± 0.0113, and 0.2547 ± 0.0104, respectively. Conclusions: Curv‐Net is evaluated on three public datasets. Extensive experimental results demonstrate that Curv‐Net outperforms the other superior curvilinear structure segmentation methods. [ABSTRACT FROM AUTHOR]

Plants often show remarkable elevational distribution patterns in arid‐montane ecosystems. However, it is not clear if soil microbes follow elevational diversity patterns, even though they represent the majority of biodiversity and drive varieties of ecological processes. Here, we conducted a survey of fungal and bacterial communities across an elevational gradient from 2350 to 3850 m in a typical mountainous grassland of arid northwestern China. Our results revealed co‐ordinated alpha and beta diversity patterns for soil microbes and plants along the elevational gradient, and the richness and Shannon diversity of bacteria, fungi, and plants exhibited a unimodal elevational pattern. The unimodal diversity pattern for soil microbes was further confirmed by the shifts in the relative abundance of dominant bacterial phyla (Actinobacteria, Firmicutes and Nitrospirae) and fungal phyla (Zygomycota) along the elevational gradient. Soil variables (soil pH, organic carbon, total nitrogen, available phosphorus, and nitrate nitrogen) explained the largest proportion of the variability in both bacterial and fungal communities, followed by plant (richness and Shannon diversity) and climatic (mean annual temperature and precipitation) variables. These environmental factors together explained a larger proportion of variability in bacterial communities (54.88%) than in fungal communities (24.15%). Our results strongly supported the existence of co‐ordinated elevational diversity patterns for soil microbes and plants in arid‐montane ecosystems, and highlighted that the importance of soil pH in microbial elevational patterns was also apparently in alkaline soils. Highlights: Soil bacteria and fungi follow elevational diversity patterns of plants.Species richness and Shannon diversity index exhibited unimodal elevational patterns.Soil, plant, and climatic factors are co‐responsible for microbial diversity.These factors explained more variation in bacteria than that in fungi.Microbial diversity is more vulnerable to precipitation than temperature. [ABSTRACT FROM AUTHOR]

Background: Human herpesvirus 6 (HHV‐6) reactivation is relatively common after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). However, the incidence of HHV‐6 reactivation and the clinical outcomes following unmanipulated haploidentical HSCT (haplo‐HSCT) remain unknown. Method: We prospectively monitored blood HHV‐6 DNA using real‐time quantitative polymerase chain reaction weekly until day 100 post unmanipulated haplo‐HSCT in patients with hematological malignancies. Results: From November 2016 to March 2017, 102 patients (58 male and 44 female, median age 25(2‐58) years old) were enrolled. Within 100 days post‐transplantation, 27 patients (27/136, 19.9%) developed HHV‐6 viremia with a median onset time of 14 (7‐98) days. The cumulative incidence of HHV‐6 reactivation on day 100 post‐HSCT was 25.5 ± 4.3% in haplo‐HSCT. The median HHV‐6 copy number was 1.45 × 103 (5.48 × 102‐2.00 × 104) copies/ml. The HHV‐6 viremia duration time was 7 days in 23 patients, 14 days in one patient and 21 days in one patient. In multivariate analysis, prior HHV‐6 reactivation was an independent risk factor for grade 2‐4 graft‐versus‐host disease (GVHD). But it did not influence the overall survival (OS)(HR 1.624, 95%CI 0.768‐3.432, P =.204), disease‐free survival (DFS) (HR 1.640, 95%CI 0.799‐3.367, P =.177) and non‐relapse mortality (NRM) (HR 1.644, 95%CI 0.670‐4.038, P =.278). Conclusion: The reactivation of HHV‐6 after unmanipulated haploidentical transplantation predicts the occurrence of grade 2‐4 a‐GVHD, but it may not influence the overall survival (OS), disease‐free survival (DFS) and non‐relapse mortality (NRM). [ABSTRACT FROM AUTHOR]

Summary: We explored the prognostic factors for children with very high‐risk (VHR) Philadelphia chromosome (Ph) negative B‐cell acute lymphoblastic leukaemia (B‐ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) as post‐remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B‐ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo‐HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3‐year overall survival (OS), disease‐free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow‐up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long‐term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative‐to‐positive MRD. Haplo‐HSCT may be an option for children with VHR Ph‐negative B‐ALL in CR1, especially for patients with persistent positive or negative‐to‐positive MRD, and could achieve better survival than intensive chemotherapy as post‐remission treatment. [ABSTRACT FROM AUTHOR]