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Purpose: Immune checkpoint inhibitors (ICIs) have improved lung cancer treatment but are associated with immune-related adverse events (irAEs). This study analyzes the relationship between irAEs and treatment effectiveness in advanced non-small cell lung cancer (NSCLC) patients. Methods: We conducted a retrospective study of NSCLC patients treated with ICIs from March 2019 to October 2022 at Zhongshan Hospital (Xiamen). Patients were divided into irAE and non-irAE groups, and treatment outcomes were compared. Results: A total of 154 patients were included, with 36.4% in the irAE group and 63.6% in the non-irAE group. Most irAEs were Grade 1–2 (86.4%), with 13.6% being Grade 3 or higher. The irAE group had higher disease control rates (DCR: 94.6% vs. 76.5%, P = 0.004) and objective response rates (ORR: 42.9% vs. 26.5%, P = 0.037). Median progression-free survival (PFS) was longer in the irAE group (18 vs. 9 months, HR: 0.53, P = 0.001), as was overall survival (OS: 39.5 vs. 16 months, HR: 0.46, P = 0.001). Landmark analysis at 6 and 12 weeks confirmed that irAEs were associated with improved outcomes. Moreover, patients who experienced two or more adverse events during treatment had significantly longer OS compared to those who had only one or no adverse events (41.6 months vs. 34.0 vs. 23.6, P = 0.003). Conclusion: Patients with irAEs demonstrated better outcomes, including ORR, DCR, PFS, and OS. Further studies on biomarkers and irAE incidence are warranted to improve lung cancer management. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents a critical stage of cardiac disease, associated with high morbidity and mortality. Cardiac resynchronization therapy (CRT) has become a pivotal treatment for HF patients with prolonged QRS duration. This therapy employs a biventricular pacing system to correct cardiac electromechanical dyssynchrony, thereby improving cardiac function, symptoms, and prognosis. Numerous clinical trials have consistently highlighted the benefits of CRT in this subgroup, leading to its unanimous recommendation in clinical practice guidelines. However, a significant proportion of patients do not achieve an adequate therapeutic response, despite adherence to these guidelines. As CRT treats patients by correcting cardiac electromechanical dyssynchrony, assessing electrical and mechanical dyssynchrony is crucial in candidate selection. This review explores the evidence, recent clinical practice guidelines, and insight into electrical and mechanical dyssynchrony to optimize CRT candidate selection in HF patients with prolonged QRS duration. [ABSTRACT FROM AUTHOR]

Through a literature review, this study investigates the responsibility, application, and impact of Artificial Intelligence (AI) in organizational training based on the theoretical frameworks of Psychological, Economic, and Systems Theories in Human Resource Development (HRD). It emphasizes the importance of responsible AI training systems that adhere to non-discrimination, privacy, interpretability, professional responsibility, and accountability to ensure AI's beneficial and equitable contribution to training. The application scenarios of AI in areas such as knowledge management, training needs analysis, training delivery, and feedback to provide personalized and efficient training solutions are analyzed. Moreover, it highlights the differing impacts of AI-supported training on organizations, trainers, and trainees and the significance of stakeholder engagement. Finally, it proposes recommendations for future research to broaden our understanding of AI's application in training and assess its effects on policies and practices, guiding organizations to adopt AI technologies per HRD principles and ethical standards. [ABSTRACT FROM AUTHOR]

In this paper, an adaptive switching anti-disturbance attitude control scheme based on improved snake optimizer (SO) is proposed for quadrotor attitude control when a quadrotor unmanned aerial vehicle is affected by measurement noise. The adaptive switching disturbance rejection controller (AWDRC) is composed of linear active disturbance rejection control and adaptive switching extended state observer which is used to achieve accurate signals reconstruction performance under measurement noise. Then, the improved SO (ISO) algorithm is developed with quadratic interpolation and comprehensive learning strategies to obtain the optimal parameters of the quadrotor attitude controller. The performance validity of ISO is demonstrated here by experiments on the CEC-2017 and the CEC-2020 benchmark functions with several state-of-the-art meta-heuristic algorithms. Secondly, the proposed ISO-based AWDRC algorithm is used in quadrotor attitude tracking control and compared with three other excellent active disturbance rejection controllers in a comparative experiment, and the experimental results show the effectiveness of the proposal. Finally, the robustness of the proposed method to parameters perturbation of the quadrotor attitude system is analyzed by Monte Carlo experiments. [ABSTRACT FROM AUTHOR]

This study aims to explore how the Metaverse platform could be applied to the field of online education, the benefits it brings, and the challenges posed by the application of Metaverse to online education. The study analyzes the benefits of immersive learning brought about by Metaverse and its potential to save education costs, enhance efficiency and students' interest in learning, and explores the application of Metaverse technology in education in relation to the characteristics of online education. The results show that Metaverse technology can support several aspects of online classrooms with realistic senses, personalized teaching models, realistic 3D identities, interactive communication, virtual reality (VR) technology, and gamified learning. This research also presents the problems faced by the Edu-Metaverse, including technology development difficulties, interaction issues, content production, game addiction, privacy, and ethics. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination. Methods: A retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis. Results: A total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis. Conclusions: For NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT's diagnostic utility in this context. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore how human resource management can be digitally transformed in the context of the digital economy. The drivers, directions, and impacts of human resource management digital transformation constitute the major study content. The study proposes that five factors—internal customer digital needs, industry digital innovation, competitor challenges, digital innovation governance, and digital era needs—drive human resource management digital transformation. It analyzes the essence of the human resource management digital transformation, such as digital workplace, digital human resource management processes, and digital employee services. Particularly, the study points out that digital human resource management processes refer to the implementation of selection, training and development, and assessment functions leveraging state-of-the-art digital technologies. It is emphasized that although digital transformation brings benefits for business development, its potential impacts cannot be ignored, including how the old and new human resource management systems are converted and the negative effects of the new system. [ABSTRACT FROM AUTHOR]

Distribution grid network has problems such as long mileage, large scale, complex surrounding environment, and aging of equipment. It is the development trend of power distribution network operation and maintenance to use unmanned aerial vehicles to patrol and combine with image processing technology for intelligent detection of equipment status. Image segmentation is well-known technique for extracting defect regions of equipment from distribution network inspection images. Therefore, this paper proposes an efficient a novel multilevel thresholding segmentation method to improve the fault diagnosis process with an improved weighted mean of vectors optimization (IINFO) algorithm. The IINFO algorithm adopts various measures to improve the optimization results, including Gaussian mutation to increase the local search ability and range of the optimal individual, Cauchy mutation to enhance the global search ability of its vector individual, reflective learning operators to strengthen self-learning and avoid local optimal solutions, and parallel operation to improve the utilization of computational resources. Moreover, two-dimensional Kapur cross-entropy is used as an objective function to solve the multilevel thresholding problem. The proposed method is evaluated using benchmark functions and distribution network inspection image datasets and is compared with 12 other metaheuristic algorithms. The results demonstrate that the proposed method has better performance and a higher ability to find optimal solutions compared to the other algorithms. These findings suggest that our method may be useful in improving the accuracy and efficiency of distribution network inspections and have significant potential for practical applications. [ABSTRACT FROM AUTHOR]

Continuous-flow microfluidic biochips are a type of biochip technology based on microfluidic channels that enable various biological experiments and analyses to be performed on a tiny chip. They have the advantages of a high throughput, high sensitivity, high precision, low cost, and quick response. In the architectural synthesis of continuous-flow microfluidic biochips (CFMBs), prior work has not considered reducing component interconnection requirements, which led to an increase in the number of connection pairs. In this paper, we propose an architectural synthesis flow for continuous-flow microfluidic biochips with connection pair optimization, which includes high-level synthesis, placement, and routing. In the high-level synthesis stage, our method reduces the need for component interconnections, which reduces the number of connection pairs. Our method performs fine-grained binding, ultimately obtaining high-quality binding and scheduling results for flow paths. Based on the high-quality binding results, we propose a port placement strategy based on port correlation and subsequently use a quadratic placer to place the components. During the routing stage, we employ a conflict-aware routing algorithm to generate flow channels to reduce conflicts between liquid transportation tasks. Experimental results on multiple benchmarks demonstrate the effectiveness of our method. Compared with the existing work, the proposed algorithm obtains average reductions of 35.34% in connection pairs, 24.30% in flow channel intersections, 21.71% in total flow channel length, and 18.39% in the execution time of bioassays. [ABSTRACT FROM AUTHOR]

This research focuses on the implementation of youth football policies in China following the 2015 national football reform. It asks the question 'To what extent have contextual and organisational factors facilitated and/or constrained the effective implementation of Chinese youth football policies?' Guided by a critical realist ontology, we conducted 23 semi-structured interviews with key stakeholders involved in the implementation process of the youth football policy including members of the national and local football associations, schools, and professional football clubs. The findings reveal a number of policy conflicts that restricted an effective implementation of the youth football policies. The main conflict lay in the ambiguous intertwinement of two dominant policy coalitions (i.e. sport and education), which consequently led to confusion and conflicts among key implementers in the three pathways. Other factors such as the continuous mismatch of traditional values and beliefs held by actors towards youth football participation, as well as the emphasis on excellence over participation by some actors are also identified as having potentially inhibited effective implementation. This paper contributes to the debate of the positioning of youth sport in an increasingly elite-driven sporting context. It argues that policymakers, implementers, and the overall society, even if they are willing to foster a positive youth sport development, can also generate an adverse effect if they do not work together. [ABSTRACT FROM AUTHOR]

The study explores the opportunities and challenges that the cross-border integration of "Metaverse + hotel" brings to visitors and the hospitality industry. The study analyses the engagement differences between Metaverse hotels and traditional online/offline strategies regarding engagement immersion, community interaction, personalization, environmental perception, and participation. Metaverse hotel brings the impact of realistic environmental simulation, personalized service, customer engagement, and consumer follow-up feedback. Further, it brings to the hospitality industry the impact of enhancing organizational performance, co-creating value for stakeholders, influencing customer relationship management, and changing how managers communicate. Finally, Metaverse technology raises challenges of security issues, technical barriers, high costs, and uncertain user needs. [ABSTRACT FROM AUTHOR]

Space exploration has drawn increasing attention to space control technology. For debris removal missions and on-orbit servicing, accurate pose estimation of a noncooperative target is critical. This article introduces the satellite relative pose estimation network (SR-Net) two-stage training method for a noncooperative target via RGB images. As the first stage in regressing the 3D translation, we combined the detection and translation regression modules into a single model. SR-Net decouples the translation and rotation information in stage two by utilizing classification instead of regression, using the detected picture as input and fitting a rotation by minimizing the weighted least squares. Furthermore, a large-scale dataset for 6-DoF pose estimation is introduced, which can be utilized as a benchmark for various state-of-the-art monocular vision-based 6-DoF pose estimation methods. Ablation studies are used to verify the effectiveness and scalability of each module. SR-Net can be added to a baseline model as a separate module to improve the 6-DoF pose estimation accuracy for noncooperative targets. The results are extremely encouraging since they show that using only vision data, it is feasible to accurately estimate the 6-DoF pose of a noncooperative target. [ABSTRACT FROM AUTHOR]

Studies on aspirin's effects on metabolic-associated fatty liver disease (MAFLD) are limited. The aim of this study was to assess the association between aspirin and all-cause and cardiovascular disease (CVD) mortality in individuals with MAFLD. Data were acquired from the National Health And Nutrition Examination Survey (NHANES) III. MAFLD diagnosis was consistent with that of international expert consensus. The independent association between aspirin and all-cause and CVD mortality in participants with MAFLD was evaluated by multiple Cox regression. Stratified analyses and interaction tests were performed to investigate whether covariates modified the association between aspirin and MAFLD mortality. Of 4594 eligible participants, 3,162 (68.83%) never took aspirin (0 times/month), 962 (20.94%) took it occasionally (1–14 times/month) and 470 (10.23%) took it regularly (≥15 times/month). Multiple cox regression showed that aspirin was not associated with overall mortality for MAFLD individuals. Stratified analysis revealed that in middle-aged (45–59 years) participants with MAFLD, occasional aspirin use was associated with low all-cause mortality risk (HR = 0.61, 95% CI = 0.43–0.86), while there was no significant association between aspirin and all-cause mortality among the young or the elderly. We found that the association between aspirin and all-cause MAFLD mortality varies by both age and frequency of administration. More prospective studies are needed to explore aspirin's influence on MALFD mortality. [ABSTRACT FROM AUTHOR]

A phosphorylcholine polymer (poly(MPC–co–BMA–co–TSMA), PMBT) was prepared by free radical polymerization and coated on the surface of the polymethylpentene hollow fiber membrane (PMP–HFM). ATR–FTIR and SEM analyses showed that the PMBT polymer containing phosphorylcholine groups was uniformly coated on the surface of the PMP–HFM. Thermogravimetric analysis showed that the PMBT had the best stability when the molar percentage of MPC monomer in the polymer was 35%. The swelling test and static contact angle test indicated that the coating had excellent hydrophilic properties. The fluorescence test results showed that the coating could resist dissolution with 90% (v/v%) ethanol solution and 1% (w/v%) SDS solution. The PMBT coating was shown to be able to decrease platelet adherence to the surface of the hollow fiber membrane, and lower the risk of blood clotting; it had good blood compatibility in tests of whole blood contact and platelet adhesion. These results show that the PMBT polymer may be coated on the surface of the PMP–HFM, and is helpful for improving the blood compatibility of membrane oxygenation. [ABSTRACT FROM AUTHOR]

First, the benefits of AI-based training for business development are presented. Then, the theoretical literature on various stages from traditional training to AI-based training is analyzed. Finally, we analyze AI applications in the training process and managerial response. This study presents a framework for the application of artificial intelligence (AI) technology to training and managerial challenges. AI tools can be applied to the training process, including knowledge management (KM), needs analysis, training organization, and results feedback. AI-based training transforms organizations into knowledge organizations that can meet the demands of personalized training and improve learning quality. AI tools bring about a shift in the training phases of knowledge base creation, needs surveys, the organization of training, and feedback on results. [ABSTRACT FROM AUTHOR]

Since the steel plate surface defect image often has complicated background and lots of noise, the segmentation accuracy is low when using the single threshold Otsu method. Therefore, this paper introduces the whale optimization algorithm (WOA) to optimize the threshold of the dual-threshold image segmentation. To avoid the premature convergence, slow convergence speed and easy fall into the local optimum of the original WOA, an improved WOA is proposed. Firstly, the WOA is discretized by using round function; secondly, the sin mapping generation chaotic sequence is used to replace the randomly generated initial population in the initialization process of the WOA to enhance the multiformity of population; thirdly, the global search and local development capabilities are balanced and improved by nonlinear time-varying factors and inertia weights in the position updating mechanism; finally, the improved WOA is applied to the two-dimensional Otsu (2D-Otsu) algorithm to select the optimal threshold for image segmentation. The simulation results of 8 classic benchmark functions show that the improved WOA can obtain the optimal value of the function 0, − 12,569.5. The improved WOA can raise convergence speed and improve the global search ability and get rid of the local optimum. The experimental results show that the proposed algorithm outperforms the Otsu algorithm and can achieve more accurate segmentation of steel plate surface defect image. Compared with 2D-Otsu algorithm, the proposed algorithm reduces running time by 0.34 s and has the highest segmentation efficiency for rolled-in scale defects. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common glioma with high mortality and poor prognosis. Radiation resistance is one of the large challenges in the treatment of glioma. The study aimed to identify whether DNA polymerase ζ affects glioma cell radiosensitivity. The mRNA and protein levels of REV3L and REV7 were examined using quantitative real-time PCR and western blot. After REV3L and REV7 knockdown in a GBM cell line (A172), we assessed cell viability, colonies, apoptosis, and immune escape. The underlying mechanisms were evaluated using western blot and were confirmed using rescue experiments. The results showed that REV3L and REV7 levels were increased in glioma and related to poor survival. γ-ray treatment inhibited cell viability, survival fraction, and immune escape, and induced apoptosis of glioma cells from a GBM cell line, whereas knockdown of REV3L or REV7 enhanced these effects. Mechanically, silencing of REV3L or REV7 inactivated the PI3K/AKT/mTOR pathway. IGF-1 treatment abrogated the effects on cell viability, colonies, and apoptosis induced by REV3L or REV7 knocking down. Taken together, silencing of REV3L and REV7 inhibited radiation resistance via inactivating the PI3K/AKT/mTOR pathway, suggesting that targeting DNA polymerase ζ may be a new strategy to reduce the radiotherapy resistance of glioma. [ABSTRACT FROM AUTHOR]

In the global war for talent, traditional recruiting methods are failing to cope with the talent competition, so employers need the right recruiting tools to fill open positions. First, we explore how talent acquisition has transitioned from digital 1.0 to 3.0 (AI-enabled) as the digital tool redesigns business. The technology of artificial intelligence has facilitated the daily work of recruiters and improved recruitment efficiency. Further, the study analyzes that AI plays an important role in each stage of recruitment, such as recruitment promotion, job search, application, screening, assessment, and coordination. Next, after interviewing with AI recruitment stakeholders (recruiters, managers, and applicants), the study discusses their acceptance criteria for each recruitment stage; stakeholders also raised concerns about AI recruitment. Finally, we suggest that managers need to be concerned about the cost of AI recruitment, legal privacy, recruitment bias, and the possibility of replacing recruiters. Overall, the study answers the following questions: (1) How artificial intelligence is used in various stages of the recruitment process. (2) Stakeholder (applicants, recruiters, managers) perceptions of AI application in recruitment. (3) Suggestions for managers to adopt AI in recruitment. In general, the discussion will contribute to the study of the use of AI in recruitment, as well as providing recommendations for implementing AI recruitment in practice. [ABSTRACT FROM AUTHOR]

System-architecture design optimization of flow-based microfluidic biochips has been extensively investigated over the past decade. Most of the prior work, however, is still based on chip architectures with dedicated storage units and this, not only limits the performance of biochips, but also increases their fabrication cost. To overcome this limitation, a distributed channel-storage architecture can be implemented, where fluid samples can be cached temporarily in flow channels instead of using a dedicated storage. This new concept of fluid storage, however, requires a careful arrangement of fluid samples to enable the channels to fulfill the dual functions of transportation and caching. Moreover, to avoid cross-contamination between different fluidic flows, wash operations are necessary to remove the residue left in flow channels. In this article, we formulate the first practical system level design and wash optimization problem for microfluidic biochips with distributed channel storage architecture, considering high-level synthesis, physical design, and wash optimization simultaneously, and present a top-down design flow to solve this problem systematically. Given the protocol of a biochemical application and the corresponding design requirements, our goal is to generate a chip architecture with low fabrication cost. Meanwhile the biochemical application can be executed efficiently with an optimized wash scheme. Experimental results on multiple benchmarks confirm that our approach leads to short completion time of biochemical applications, low chip cost, as well as high wash efficiency. [ABSTRACT FROM AUTHOR]

The pandemic has changed the way people work, and more and more people are choosing to work from home (WFH). Unlike traditional work patterns, this approach has limitations and has had a significant impact on both organizations and individuals. It also brings many challenges to the work of HR practitioners. HR practitioners, as key players in strategic human resource management, need to take advantage of management innovations under the crisis to improve employees' work flexibility and effectively address the impact of working from home. This study aims to address the need for employee skill improvement, psychological stress relief, work-family balance, and company culture reinforcement from an HRM perspective because of the impact of WFH work patterns during the COVID-19 crisis. [ABSTRACT FROM AUTHOR]

With the explosion of coronavirus disease 2019 (COVID-19), the concept of "Sharing Employees" has emerged in China. This study will discuss the background of the formation of the "Sharing Employees," how the "Sharing Employees" model is implemented, the relative risks, and the impact on human resource management. Currently, this virus is spreading worldwide, affecting the economy and increasing the unemployment rate. This study will help other countries to learn from this model and provide suggestions for adopting flexible employment policies to ease employment pressure and increase employment channels through the "Sharing Employees" B2B model. [ABSTRACT FROM AUTHOR]

In this paper, the problem of the robust tracking for two-arm condenser cleaning crawler-type mobile manipulators (CCCMM) with delayed angle-velocity uncertainties is original investigated. The two-arm condenser cleaning crawler-type mobile manipulators are composed of a crawler-type mobile platform and two-arm industrial manipulators.The uncertainty is nonlinear time-varying and does not require a matching condition. A wavelet transform and probabilistic neural network (WTPNN) system is used to approximate an unknown controlled system from the strategic manipulation of the model following tracking errors. Based on the Lyapunov method and the linear matrix inequality (LMI) approach, several sufficient conditions, which guarantee the state variables of the closed loop system to converge, globally, uniformly and exponentially, to a ball in the state space with any pre-specified convergence rate, are derived. Experiment results are given to illustrate the superior control performance of the proposed intelligent control method. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant to infection. Here, we generated FMDV-specific shRNA transgenic cells targeting either nonstructural protein 2B or polymerase 3D of FMDV. The shRNA-positive transgenic cells displayed significantly lower viral production than that of the control cells after infection with FMDV (P < 0.05). Twenty-three transgenic cloned swine (TGCS) and nine non-transgenic cloned swine (Non-TGCS) were produced by somatic cell nuclear transfer (SCNT). In the FMDV challenge study, one TGCS was completely protected, no clinical signs, no viremia and no viral RNA in the tissues, no non-structural antibody response, another one TGCS swine recovered after showing clinical signs for two days, whereas all of the normal control swine (NS) and Non-TGCS developed typical clinical signs, viremia and viral RNA was determined in the tissues, the non-structural antibody was determined, and one Non-TGCS swine died. The viral RNA load in the blood and tissues of the TGCS was reduced in both challenge doses. These results indicated that the TGCS displayed resistance to the FMDV infection. Immune cells, including CD3+, CD4+, CD8+, CD21+, and CD172+ cells, and the production of IFN-γ were analyzed, there were no significant differences observed between the TGCS and NS or Non-TGCS, suggesting that the FMDV resistance may be mainly derived from the RNAi-based antiviral pathway. Our work provides a foundation for a breeding approach to preventing infectious disease in swine. [ABSTRACT FROM AUTHOR]

Background: Exosomes, internal proteins, lipids, and nucleic acids coated by phospholipid bilayer membranes, are one type of small extracellular vesicles, which can mediate cell-cell communication. In recent years, exosomes have gained considerable scientific interest due to their widely applied prospect in the diagnosis and therapeutics of human and animal diseases. In this study, we describe for the first time a feasible method designed to isolate and characterize exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells. Results: Exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells were successfully isolated by differential centrifugation. Quantification and sizing of exosomes were assessed by transmission electron microscopy, flow nano analysis and western blotting. Detected particles showed the normal size (30–100 nm) and morphology described for exosomes, as well as presence of the transmembrane protein (TSG101, CD9, CD63, and CD81) known as exosomal marker. Conclusions: The results suggest that differential centrifugation is a feasible method for isolation of exosomes from different types of feline samples. Moreover, these exosomes can be used to further diagnosis and therapeutics in veterinary pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. Results: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs. Conclusions: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has quickly spread throughout the country and the world since first broke out in Wuhan, China. The outbreak that started from January 22, 2020, in Fujian Province has been controlled as the number of indigenous cases has not increased since March. We aimed to describe the clinical characteristics of patients with COVID-19 in Fujian Province, China. Methods: In this retrospective, multicenter study, we collected and analyzed the epidemiological, clinical, and laboratory data of all cases confirmed by nucleic acid tests in five designated hospitals in Fujian Province between January 22 and February 27, 2020. All patients were followed up until discharge. COVID-19 severity was classified as mild, moderate, severe, or critical. Results: Of 199 discharged patients with COVID-19, 105 patients were male, with a median age of 46.3 years, and 17 patients were severe, and 5 patients were critical on admission. Hypertension and diabetes were the most common comorbidities. The symptoms at illness onset were mainly fever (76.4%), cough (60.8%), and myalgia or fatigue (27.6%). A total of 96.5% of patients had abnormal imaging findings on chest computed tomography. Lymphopenia (37.2%) and hypoxemia (13.6%) were observed. Acute respiratory distress syndrome and respiratory failure occurred in 9 patients (4.5%) and 8 patients (4.0%) respectively. One patient died and the others were cured and discharged with the median hospital stay of 19 days. Old age was negatively correlated with lymphocyte count (r = - 0.296, p < 0.001) and oxygenation index (r = - 0.263, p = 0.001). Bivariate regression analysis revealed that old age (≥ 75 years), hypertension, diabetes, and lymphopenia were correlated with the severity of COVID-19. Conclusions: Patients in Fujian Province were mostly nonsevere cases with mild or moderate symptoms, and had a lower mortality than patients in Wuhan (4.3%-15%). Older age, hypertension, diabetes, and lymphopenia were risk factors for severity of COVID-19. [ABSTRACT FROM AUTHOR]

The Steiner minimal tree (SMT) problem is an NP-hard problem, which is the best connection model for a multi-terminal net in global routing problem. This paper presents a unified algorithm for octagonal and rectilinear SMT construction based on hybrid transformation strategy (HTS) and self-adapting particle swarm optimization. Firstly, an effective HTS is proposed to enlarge the search space and improve the convergence speed. Secondly, the proposed HTS in the evolutionary process may produce an ineffective solution, and consequently the crossover and mutation operators of genetic algorithm (GA) based on union-find sets is proposed. Thirdly, a self-adapting strategy that can adjust the acceleration coefficients is proposed to further improve the convergence and the quality of the proposed algorithm. Finally, the hybrid transformation can be applied to GA and the proposed algorithm can be applied to rectilinear architecture. To our best knowledge, the proposed algorithm is the first unified algorithm to solve the SMT construction under both octagonal and rectilinear architecture. The experimental results show that the proposed algorithm can efficiently provide a better solution for SMT problem both in octagonal and rectilinear architectures than others. Moreover, the algorithm can obtain several topologies of SMT, which is beneficial for optimizing congestion in VLSI global routing stage. [ABSTRACT FROM AUTHOR]

A new Zn-based metal–organic framework with 8-connected hex topology constructed from bipyridine and carboxylate ligands, namely [Zn(cpna)3(tmbpy)]n·4DMF (1) (H2cpna = 6-(4-carboxyphenyl)nicotinic acid; tmbpy = 3,3′-dimethyl-4,4′-bipyridine), has been synthesized under solvothermal conditions. The Zn-MOF was structurally characterized and retained a good crystal structure after activation (1a), an indication of permanent porosity. 1a exhibits a BET surface of 770 m2 g−1 and the maximum aperture of 8.60 Å. Single component adsorption isotherm measurements of C2H2, CO2, CH4, CO and N2 on 1a were performed both at 273 K and 298 K, and the selectivities for C2H2/CH4, C2H2/CO2, CO2/CO, CO2/CH4 and CO2/N2 were estimated on the basis of the ideal adsorbed solution theory (IAST). 1a shows the uptake of C2H2 (3.89 mmol g−1) and CO2 (3.52 mmol g−1) at 273 K and 100 kPa, respectively. Due to the Lewis basic pyridyl sites inside the channel of the framework, 1a showed good adsorption selectivities for C2H2/CH4(50 : 50) and C2H2/CO2(50 : 50) at 298 K (100 kPa). [ABSTRACT FROM AUTHOR]

Introduction: Targeted therapies are based on specific gene alterations. Various specimen types have been used to determine gene alterations, however, no systemic comparisons have yet been made. Herein, we assessed alterations in selected cancer‐associated genes across varying sample sites in lung cancer patients. Materials and Methods: Targeted deep sequencing for 48 tumor‐related genes was applied to 153 samples from 55 lung cancer patients obtained from six sources: Formalin‐fixed paraffin‐embedded (FFPE) tumor tissues, pleural effusion supernatant (PES) and pleural effusion cell sediments (PEC), white blood cells (WBCs), oral epithelial cells (OECs), and plasma. Results: Mutations were detected in 96% (53/55) of the patients and in 83% (40/48) of the selected genes. Each sample type exhibited a characteristic mutational pattern. As anticipated, TP53 was the most affected sequence (54.5% patients), however this was followed by NOTCH1 (36%, across all sample types). EGFR was altered in patient samples at a frequency of 32.7% and KRAS 10.9%. This high EGFR/ low KRAS frequency is in accordance with other TCGA cohorts of Asian origin but differs from the Caucasian population where KRAS is the more dominant mutation. Additionally, 66% (31/47) of PEC samples had copy number variants (CNVs) in at least one gene. Unlike the concurrent loss and gain in most genes, herein NOTCH1 loss was identified in 21% patients, with no gain observed. Based on the relative prevalence of mutations and CNVs, we divided lung cancer patients into SNV‐dominated, CNV‐dominated, and codominated groups. Conclusions: Our results confirm previous reports that EGFR mutations are more prevalent than KRAS in Chinese lung cancer patients. NOTCH1 gene alterations are more common than previously reported and reveals a role of NOTCH1 modifications in tumor metastasis. Furthermore, genetic material from malignant pleural effusion cell sediments may be a noninvasive manner to identify CNV and participate in treatment decisions. [ABSTRACT FROM AUTHOR]

Parthenogenetic embryonic stem (pES) cells isolated from parthenogenetic activation of oocytes and embryos, also called parthenogenetically induced pluripotent stem cells, exhibit pluripotency evidenced by both in vitro and in vivo differentiation potential. Differential proteomic analysis was performed using differential in-gel electrophoresis and isotope-coded affinity tag-based quantitative proteomics to investigate the molecular mechanisms underlying the developmental pluripotency of pES cells and to compare the protein expression of pES cells generated from either the in vivo-matured ovulated (IVO) oocytes or from the in vitro-matured (IVM) oocytes with that of fertilized embryonic stem (fES) cells derived from fertilized embryos. A total of 76 proteins were upregulated and 16 proteins were downregulated in the IVM pES cells, whereas 91 proteins were upregulated and 9 were downregulated in the IVO pES cells based on a minimal 1.5-fold change as the cutoff value. No distinct pathways were found in the differentially expressed proteins except for those involved in metabolism and physiological processes. Notably, no differences were found in the protein expression of imprinted genes between the pES and fES cells, suggesting that genomic imprinting can be corrected in the pES cells at least at the early passages. The germline competent IVM pES cells may be applicable for germ cell renewal in aging ovaries if oocytes are retrieved at a younger age. [ABSTRACT FROM AUTHOR]

Mammalian parthenogenesis could not survive but aborted during mid-gestation, presumably because of lack of paternal gene expression. To understand the molecular mechanisms underlying the failure of parthenogenesis at early stages of development, we performed global gene expression profiling and functional analysis of parthenogenetic blastocysts in comparison with those of blastocysts from normally fertilized embryos. Parthenogenetic blastocysts exhibited changes in the expression of 749 genes, of which 214 had lower expression and 535 showed higher expressions than fertilized embryos using a minimal 1.8-fold change as a cutoff. Genes important for placenta development were decreased in their expression in parthenote blastocysts. Some maternally expressed genes were up-regulated and paternal-related genes were down-regulated. Moreover, aberrantly increased Wnt signaling and reduced mitogen-activated protein kinase (MAPK) signaling were associated with early parthenogenesis. The protein level of extracellular signal-regulated kinase 2 (ERK2) was low in parthenogenetic blastocysts compared with that of fertilized blastocysts 120 h after fertilization. 6-Bromoindirubin-3′-oxime, a specific glycogen synthase kinase-3 (GSK-3) inhibitor, significantly decreased embryo hatching. The expression of several imprinted genes was altered in parthenote blastocysts. Gene expression also linked reduced expression of Xist to activation of X chromosome. Our findings suggest that failed X inactivation, aberrant imprinting, decreased ERK/MAPK signaling and possibly elevated Wnt signaling, and reduced expression of genes for placental development collectively may contribute to abnormal placenta formation and failed fetal development in parthenogenetic embryos. [ABSTRACT FROM PUBLISHER]

Three-dimensional vertical resistive random access memory (VRRAM) is proposed as a promising candidate for increasing resistive memory storage density, but the performance evaluation mechanism of 3-D VRRAM arrays is still not mature enough. The previous approach to evaluating the performance of 3-D VRRAM was based on the write and read margin. However, the leakage current (LC) of the 3-D VRRAM array is a concern as well. Excess leakage currents not only reduce the read/write tolerance and liability of the memory cell but also increase the power consumption of the entire array. In this article, a 3-D circuit HSPICE simulation is used to analyze the impact of the array size and operation voltage on the leakage current in the 3-D VRRAM architecture. The simulation results show that rapidly increasing leakage currents significantly affect the size of 3-D layers. A high read voltage is profitable for enhancing the read margin. However, the leakage current also increases. Alleviating this conflict requires a trade-off when setting the input voltage. A method to improve the array read/write efficiency is proposed by analyzing the influence of the multi-bit operations on the overall leakage current. Finally, this paper explores different methods to reduce the leakage current in the 3-D VRRAM array. The leakage current model proposed in this paper provides an efficient performance prediction solution for the initial design of 3-D VRRAM arrays. [ABSTRACT FROM AUTHOR]