Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management

Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape

Optimal automobile distribution model in multimodal freight transportation networks

This paper proposes a novel optimal automobile distribution problem for a large automobile manufacturer. The proposed problem concerns the cost-effective distribution of automobiles to vehicle distribution centers and vehicle storage centers in a multimodal freight transportation network including truck, rail, and ship modes by taking into account practical service frequencies and the capacities of ships and trains, multiple batches daily delivery, and demanded delivery time. The problem is formulated as an integer linear programming model, which can be solved efficiently by an optimization solver such as CPLEX. A case study created by the Shanghai Automobile Industry Corporation is carried out to assess the applicability and performance of the model developed in this study

Short-term Efficacy of Hand-Arm Bimanual Intensive Training on Upper Arm Function in Acute Stroke Patients: A Randomized Controlled Trial

BackgroundRehabilitation training during the acute phase of stroke (<48 h) markedly improves impaired upper-limb movement. Hand-arm bimanual intensive training (HABIT) represents an intervention that promotes improvements in upper extremity function in children with cerebral palsy. This study repurposed HABIT in acute stroke patients and assessed recovery of upper extremity function when compared with a conventional rehabilitation program (CRP).MethodsIn a randomized trial, 128 patients with acute stroke were assigned to the HABIT or the CRP groups. The primary endpoint was clinical motor functional assessment that was guided by the Fugl-Meyer motor assessment (FMA) and outcomes of the action research arm test (ARAT). The secondary endpoint was an improved neurophysiological evaluation according to the motor-evoked potential amplitude (AMP), resting motion threshold (RMT), and central motor conduction time (CMCT) scores over the 2-week course of therapy. In both groups, scores were evaluated at baseline, 1 week from commencing therapy, and post-therapy.ResultsAfter 2 weeks, the HABIT group showed improved scores as compared the CRP group for FMA (51.7 ± 6.44 vs. 43.5 ± 5.6, P < 0.001), ARAT (34.5 ± 6.2 vs. 33.3 ± 6.3, P = 0.022), and AMP (1.1 ± 0.1 vs. 1.0 ± 0.1, P < 0.001). However, CMCT (8.6 ± 1.0 vs. 9.1 ± 0.6, P = 0.054) and RMT (55.3 ± 4.2 vs. 57.5 ± 4.1, P = 0.088) were similar when comparing between groups.ConclusionHABIT significantly improved motor functional and neuro-physiological outcomes in patients with acute stroke, which suggested that HABIT might represent an improved therapeutic strategy as compared CRP

A double-channel multiscale depthwise separable convolutional neural network for abnormal gait recognition

Abnormal gait recognition is important for detecting body part weakness and diagnosing diseases. The abnormal gait hides a considerable amount of information. In order to extract the fine, spatial feature information in the abnormal gait and reduce the computational cost arising from excessive network parameters, this paper proposes a double-channel multiscale depthwise separable convolutional neural network (DCMSDSCNN) for abnormal gait recognition. The method designs a multiscale depthwise feature extraction block (MDB), uses depthwise separable convolution (DSC) instead of standard convolution in the module and introduces the Bottleneck (BK) structure to optimize the MDB. The module achieves the extraction of effective features of abnormal gaits at different scales, and reduces the computational cost of the network. Experimental results show that the gait recognition accuracy is up to 99.60%, while the memory size of the model is reduced 4.21 times than before optimization

The Preparation, Microstructure, and Wet Wear Properties of an Fe55-Based Welding Layer with the Co-Addition of 0.01 wt% CeO₂ and 1.5 wt% SiC Particles Using the Plasma Beam Spraying Method

Severe erosion wear is found on valve spools, which threatens the safety and reliability of these units. The use of the plasma beam spraying surfacing method can significantly improve the corrosion resistance and sealing performance of hydraulic valve spools, reduce material waste, and reduce maintenance costs. The effects of the co-addition of CeO2 and SiC particles on the morphology, surface cracks, microstructure, precipitated phases, and wear property of plasma-beam-sprayed Fe55-based coatings on 1025 steel were investigated using OM, EDS, ultra-deep field microscopy, and a wet sand rubber wheel friction tester, respectively. The dendrite exhibited a directional growth pattern perpendicular to the substrate and the transitional states of the microstructure with the co-addition of CeO2 and SiC particles. CeO2 or SiC reduced the liquid phase diffusion coefficient DL of Cr and C and resulted in a decrease in the G/R ratio. The dendrites changed into equiaxed grains. The main phase composition of the Fe55 welding layer was Cr7C3, γ-Fe. The martensite in the surfacing layer and the carbides formed Cr7C3, which can improve the hardness of the surfacing layer. The grain boundaries consisted mainly of a reticular eutectic structure. The uniform distribution of the Cr7C3 hard phase in the Fe55+1.5 wt% SiC+0.01 wt% CeO2 resulted in a uniformly worn surface. The sub-wear mechanisms during the friction process were micro-ploughing and micro-cutting. The hardness and toughness of Fe55+1.5 wt% SiC+0.01 wt% CeO2 were well-matched, avoiding excessive micro-cutting and microplastic deformation. A low content of CeO2 could lead to the formation of equiaxed grain and effectively improve the uniformity of the microstructure. The wear-resistant layer of Fe55+1.5 wt% SiC+0.01 wt% CeO2 can effectively improve the service life and long-term sealing performance of the valve spools

Novel DnaJ Protein Facilitates Thermotolerance of Transgenic Tomatoes

DnaJ proteins, which are molecular chaperones that are widely present in plants, can respond to various environmental stresses. At present, the function of DnaJ proteins was studied in many plant species, but only a few studies were conducted in tomato. Here, we examined the functions of a novel tomato (Solanum lycopersicum) DnaJ protein (SlDnaJ20) in heat tolerance using sense and antisense transgenic tomatoes. Transient conversion assays of Arabidopsis protoplasts showed that SlDnaJ20 was targeted to chloroplasts. Expression analysis showed that SlDnaJ20 expression was induced by chilling, NaCl, polyethylene glycol, and H2O2, especially via heat stress. Under heat stress, sense plants showed higher fresh weights, chlorophyll content, fluorescence (Fv/Fm), and D1 protein levels, and a lower accumulation of reactive oxygen species (ROS) than antisense plants. These results suggest that SlDnaJ20 overexpression can reduce the photoinhibition of photosystem II (PSII) by relieving ROS accumulation. Moreover, higher expression levels of HsfA1 and HsfB1 were observed under heat stress in sense plants, indicating that SlDnaJ20 overexpression contributes to HSF expression. The yeast two-hybrid system proved that SlDnaJ20 can interact with the chloroplast heat-shock protein 70. Our results indicate that SlDnaJ20 overexpression enhances the thermotolerance of transgenic tomatoes, whereas suppression of SlDnaJ20 increases the heat sensitivity of transgenic tomatoes