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The electrification of shared mobility has become popular across the globe. Many cities have their new shared e-mobility systems deployed, with continuously expanding coverage from central areas to the city edges. A key challenge in the operation of these systems is fleet rebalancing, i.e., how EVs should be repositioned to better satisfy future demand. This is particularly challenging in the context of expanding systems, because i) the range of the EVs is limited while charging time is typically long, which constrain the viable rebalancing operations; and ii) the EV stations in the system are dynamically changing, i.e., the legitimate targets for rebalancing operations can vary over time. We tackle these challenges by first investigating rich sets of data collected from a real-world shared e-mobility system for one year, analyzing the operation model, usage patterns and expansion dynamics of this new mobility mode. With the learned knowledge we design a high-fidelity simulator, which is able to abstract key operation details of EV sharing at fine granularity. Then we model the rebalancing task for shared e-mobility systems under continuous expansion as a Multi-Agent Reinforcement Learning (MARL) problem, which directly takes the range and charging properties of the EVs into account. We further propose a novel policy optimization approach with action cascading, which is able to cope with the expansion dynamics and solve the formulated MARL. We evaluate the proposed approach extensively, and experimental results show that our approach outperforms the state-of-the-art, offering significant performance gain in both satisfied demand and net revenue.

Artificial bone materials are in great need due to a lot of bone injuries. Herein, collagen/nano-hydroxyapatite (Col/nHA, C-H) composite nanospheres were obtained by in-situ mineralization, and poly L-lactic acid/collagen/nano-hydroxyapatite (PLLA/Col/nHA, P-C-H) was further prepared by high-speed shear emulsification method. The interfacial properties and structure between PLLA and nHA are regulated by the adhesive property of Col. The morphology, structure and properties of P-C-H microsphere were characterized in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) and simulated degradation of PBS in vitro. The results show that C-H is uniformly distributed in P-C-H microspheres, and a mesoporous material with a "pomegranate" structure and a particle size of 5-30 μm is self-assembled based on C-H multiple composite microspheres. It is beneficial to the sustained-release degradation of P-C-H and the retention/release of Ca

The wearable and portable Electroencephalogram (EEG) sensing systems are deeply interfered by unavoidable physiological artifacts due to the limited recording resources. In this work, an intelligent artifact removal system that handles single-channel EEG signals in the presence of mixed multi-type artifacts is investigated.The basic idea is to represent the mixed artifacts in contaminated varying EEG signals with the unchanged latent pattern features, and then employ the adaptive artifact removal scheme to separate the contamination and clean EEG signals in the encoded feature domain. To minimize the risks of corrupting clean signals and keeping artifacts by mistake, the artifact removal is formulated as an identification-removal two-stage minimization problem, and an attention based adaptive feature concentration mechanism is designed to improve the removal utility and reduce the calculation consumption.In the real implementation on open real-world dataset, this study achieves the artifact identification accuracy of 98.52% and average correlation coefficient of 0.73 for the removal of strong mixed multi-type artifacts.This study can deal with single-channel EEG signals contaminated by mixed multi-type artifacts with high accuracy and low overhead, and is more effective and stable than traditional schemes with fixed criteria.This study can significantly improve the signal quality acquired by simplified EEG sensing systems, and may extend the application of wearable and portable EEG sensing systems to medical diagnosis, cognitive science research and other applications requiring clinical setups.

The yield and quality of potatoes, an important staple crop, are seriously threatened by high temperature and drought stress. In order to deal with this adverse environment, plants have evolved a series of response mechanisms. However, the molecular mechanism of potato’s response to environmental changes at the translational level is still unclear. In this study, we performed transcriptome- and ribosome-profiling assays with potato seedlings growing under normal, drought, and high-temperature conditions to reveal the dynamic translational landscapes for the first time. The translational efficiency was significantly affected by drought and heat stress in potato. A relatively high correlation (0.88 and 0.82 for drought and heat stress, respectively) of the fold changes of gene expression was observed between the transcriptional level and translational level globally based on the ribosome-profiling and RNA-seq data. However, only 41.58% and 27.69% of the different expressed genes were shared by transcription and translation in drought and heat stress, respectively, suggesting that the transcription or translation process can be changed independently. In total, the translational efficiency of 151 (83 and 68 for drought and heat, respectively) genes was significantly changed. In addition, sequence features, including GC content, sequence length, and normalized minimal free energy, significantly affected the translational efficiencies of genes. In addition, 28,490 upstream open reading frames (uORFs) were detected on 6463 genes, with an average of 4.4 uORFs per gene and a median length of 100 bp. These uORFs significantly affected the translational efficiency of downstream major open reading frames (mORFs). These results provide new information and directions for analyzing the molecular regulatory network of potato seedlings in response to drought and heat stress.

While overweight/obesity has become a major public health issue worldwide, any association between body mass index (BMI) and therapeutic response in neoadjuvant targeted therapy treated HER2 positive breast cancer patients remain unclear. The information from a total of four-hundred and ninety-one neoadjuvant targeted therapy treated HER2 positive breast cancer patients from four institutions were retrospectively collected. Univariate and multivariate logistic analysis was developed to determine the association between BMI and therapeutic response. A meta-analysis of published literature was then conducted to confirm the effect of overweight/obesity on pCR for patients treated with neoadjuvant targeted therapy. Restricted cubic spline (RCS) adjusted for confounding factors demonstrated a decrease pCR with increasing BMI (OR = 0.937, P = 0.045). Patients were then categorized into under/normal weight (n = 299) and overweight/obesity (n = 192). Overweight/obese patients were independently associated with a poor therapeutic response. In the subgroup analysis, a significant negative impact of overweight/obesity on pCR can be observed both in single-targeted (OR = 0.556; P = 0.02) and dual-targeted (OR = 0.392; P = 0.021) populations. Six eligible studies involving 984 neoadjuvant targeted therapy treated HER2 positive breast cancer patients were included in the meta-analysis. The meta-analysis also demonstrated that overweight/obesity was significantly associated with a poor response to neoadjuvant anti-HER2 therapy (OR = 0.68; P = 0.007). Our result show that overweight and obese HER2 positive breast cancer patients are less likely to achieve pCR after neoadjuvant targeted therapy.

BackgroundMyositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear.MethodsA total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes.ResultsThere were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis.ConclusionGene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Background Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated. Methods The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan–Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models. Results BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038–1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163–4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218–4.913], P = 0.011). Conclusions For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.

Background: The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer. Methods: Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification. Results: HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration. Conclusions: We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.

3D flower-like nitrogen and sulfur co-doped carbon nanosheets (N,S-CNS) were prepared with tunable heteroatom doping and graphitic structures. An “adsorption–insertion” model was proposed for well explaining the potassium storage behaviors.

Introduction: Physical training is essential to physical fitness in freestyle skiers. The domain of stability in the technical movements is a determinant of the competition, always constantly improving. Objective: Develop a physical training program adapted to freestyle skiing. Methods: Twelve freestyle skiers were selected as volunteers for the experiment. This paper compares athletes’ physical qualities and individual abilities before and after physical training. Through recent research, the athletes’ physical condition was comprehensively evaluated to test the effectiveness of their physical training. results: Freestyle skiers showed good anaerobic fitness. A relationship was found between the maximum number of thrusts, the degree of spin in the air, the maximum power duration, and the power decay rate (P0.05). Conclusion: This paper systematically studies body composition, the center of gravity strength, anaerobic capacity, and balance in freestyle skiers. The results provide a good assessment of the effect of fitness training on freestyle ski athletes. These results have particular guiding significance for formulating and implementing training programs focused on the sport. Level of evidence II; Therapeutic studies - investigation of treatment outcomes. RESUMO Introdução: O treinamento físico é parte essencial da aptidão física em esquiadores de estilo livre. O domínio da estabilidade nos movimentos técnicos é determinante sobre as competições, estando sempre em constante aprimoramento. Objetivo: Elaborar um programa de treinamento físico adaptado ao esporte do esqui de estilo livre. Métodos: Selecionou-se 12 esquiadores de estilo livre como voluntários ao experimento. Este artigo compara as qualidades físicas e habilidades individuais dos atletas antes e depois do treinamento físico. Através de pesquisas recentes, avaliou-se de forma abrangente a condição física dos atletas para testar a eficácia de seu treinamento físico. Resultados: Os esquiadores de estilo livre apresentaram uma boa praticabilidade anaeróbica. Foi encontrada uma relação particular entre o número máximo de propulsões e o grau de giro no ar, a duração máxima da potência e a taxa de decaimento da potência (P0,05). Conclusão: Este artigo fornece um estudo sistemático da composição corporal, força do centro gravitacional, capacidade anaeróbica e equilíbrio em esquiadores de estilo livre. Os resultados proporcionam uma boa avaliação do efeito de treinamento de aptidão física nos atletas de esqui de estilo livre. Estes resultados têm um significado orientador particular para a formulação e implementação de programas de treinamento focados na modalidade. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento. RESUMEN Introducción: El entrenamiento físico es una parte esencial de la aptitud física en los esquiadores de estilo libre. El dominio de la estabilidad en los movimientos técnicos es determinante sobre las competiciones, estando siempre en constante mejora. Objetivo: Desarrollar un programa de entrenamiento físico adaptado al deporte del esquí de estilo libre. Métodos: Se seleccionaron doce esquiadores de estilo libre como voluntarios para el experimento. Este artículo compara las cualidades físicas y las capacidades individuales de los atletas antes y después del entrenamiento físico. Mediante una investigación reciente, se evaluó exhaustivamente la condición física de los atletas para comprobar la eficacia de su entrenamiento físico. Resultados: Los esquiadores de estilo libre mostraron una buena aptitud anaeróbica. Se encontró una relación particular entre el número máximo de empujes y el grado de giro en el aire, la duración de la potencia máxima y la tasa de disminución de la potencia (P0,05). Conclusión: Este artículo proporciona un estudio sistemático de la composición corporal, la fuerza gravitatoria central, la capacidad anaeróbica y el equilibrio en esquiadores de estilo libre. Los resultados proporcionan una buena evaluación del efecto del entrenamiento físico en los atletas de esquí de estilo libre. Estos resultados tienen una especial importancia orientativa para la formulación y aplicación de programas de entrenamiento centrados en este deporte. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The state-of-art progress of alloy-type anodes for potassium-ion batteries and their K+ storage mechanism and structure-property relationship are summarized.

Signals from gyros and accelerometers in an inertial navigation system (INS) can be processed to obtain navigation information while its errors accumulate with time. A path with long‐term characteristics is more likely to encounter unpredictable dynamic conditions. To deal with such problems, this work improves the global static path‐planning algorithm based on the A* algorithm, and the local dynamic path‐planning algorithm based on dynamic window approach (DWA). In the global planning algorithm, the gravity index and the heading index are incorporated into the cost function of the A* algorithm to consider the mismatches and the deflection of the path. Furthermore, the search method of the A* algorithm is also improved. In the local planning algorithm, the motion model of the DWA algorithm is improved to a high‐precision model and expressed in a geographic coordinate system. Finally, the improved global static planning and local dynamic planning are combined as the global dynamic path‐planning algorithm of an underwater vehicle. The simulation results show that the global dynamic path‐planning algorithm proposed can realise obstacle‐free navigation of the underwater vehicle.

IntroductionTissue-resident macrophages (TRMs) are highly heterogeneous and have a complex and important role in tissue support, homeostasis, and function. The heterogeneity, maintenance, and function of TRMs, as one of the major immune cells in the ovary, are not well understood.MethodsApplication of flow cytometry, Parabiosis, Fate mapping, Macrophage depletion, etc.ResultsHere, we described two distinct macrophage subsets, F4/80hiCD11bint and F4/80intCD11bhi, with different phenotypic characteristics in the ovary of mice. The F4/80hiCD11bint population contained a distinct CD206+ subgroup and highly expressed CD81, while the F4/80intCD11bhi subset showed higher expression of CCR2 and TLR2. Notably, Ly6c+ macrophages were present almost exclusively in the F4/80intCD11bhi subpopulation. Combining in vivo fate mapping and parabiotic mouse models, we characterized the longevity and replenishment of the two macrophage populations. We found that both the F4/80hiCD11bint and F4/80intCD11bhi subsets were ovary-resident. Importantly, the F4/80hiCD11bint macrophages acted as a self-maintaining and long-lived population with a modest monocyte contribution at a steady state, and the F4/80intCD11bhi subpopulation had a relatively short lifespan with a greater contribution from monocytes. After macrophage ablation, disturbance of estradiol secretion and ovarian hemorrhage due to damaged vascular integrity was observed in mice.DiscussionOur data provide critical insights into ovarian macrophage heterogeneity and highlight the strategic role of TRMs in ovarian homeostasis and physiology.

With climate change and global warming, there are extreme weather phenomena in some places. Excessive temperature can adversely affect room temperature vulcanized silicone rubber (RTV) insulators. Other factors such as air pollution, dust, fog, rain, ice and snow, and ultraviolet rays can cause damage to the surface hydrophobicity of the RTV surface and reduce its service life. Contamination from the above factors increases the risk of flashover and corona discharge, which can lead to accidents in the transmission system, resulting in economic loss or personal injury. In recent decades, scientists have investigated a variety of materials that can be compounded with RTV to improve their chemical and physical properties in order to extend the service life of RTV insulators. In this review, we conduct an extensive literature survey and summary on the development and application of RTV coated insulators.

Due to the large ionic radius and associated slow reaction kinetics of potassium ions, it is a major challenge to find suitable anode materials for potassium-ion batteries. Herein, we design porous antimony-based nanofibres via a simple, low-cost and large scalable method to promote the electrochemical performance of potassium-ion batteries. Unlike those traditionally treated in inert atmospheres, using the different decomposition processes of polyacrylonitrile and polyvinylpyrrolidone in air, we obtain antimony trioxide embedded in porous carbon nanofibres (Sb

We describe the case of a 4-month-old boy who presented with bilateral congenital cataract and high intraocular pressure (IOP) in the left eye, followed by mental retardation and delayed motor development. Genetic investigation revealed the boy had a splicing variant (c.940-11G>A) of the oculocerebrorenal syndrome of Lowe (OCRL) gene. The boy underwent a lensectomy for congenital cataract in his right eye, and lensectomy combined with a 360° suture trabeculotomy to remove the clouded lens and to control IOP of the left eye. During postoperative one-and-a-half-year follow-up, the boy exhibited an improved visual acuity and a well-controlled IOP without the use of topical IOP-lowering medications. Lowe syndrome is a rare multisystemic disorder that is diagnosed through clinical manifestation and genetic testing. The possibility of Lowe syndrome should be considered in patients presenting with typical triad, and genetic analysis should be performed in time to confirm the diagnosis. We recommend combined cataract surgery and minimally invasive glaucoma surgery (MIGS) as a safe, feasible, and efficient method to treat congenital cataract and glaucoma in Lowe syndrome patients.

The preparation of freestanding electrodes with excellent conductivity and mechanical strength plays a vital role in simplifying the electrode fabrication process and reducing the electrode cost. H...

Potassium-ion batteries (PIBs) have the potential to be used in future large-scale energy storage devices because of the abundance of potassium resources and their relatively high energy density. However, low reversible capacity and poor cycling stability caused by the large size of the potassium ions limit their practical application. N-doped bacterial cellulose-derived carbons (NBCCs) were prepared by impregnating bacterial cellulose with Mg(NO3)2 solutions (0.03, 0.05 and 0.07 mol L−1) as a pore template and nitrogen source, followed by carbonization and acid washing. The effects of the Mg(NO3)2 concentration on the morphology, porosity, N doping level and electrochemical performance of the NBCCs were investigated. NBCC (0.05) is the best of the three because it has an interconnected pore network structure with a homogeneous distribution of N at a concentration of 3.38 at% and a high specific surface area of 1355 m2 g−1. It delivers an excellent rate capability of 134 mAh g−1 at 5 A g−1 and a capacity of 307 mAh g−1 after 2500 cycles at 2 A g−1. A NBCC (0.05)-based anode in a potassium ion hybrid capacitor has a high energy density of 166 W h kg−1 at a power density 493 W kg−1 and excellent cyclability with a capacityretention of nearly 95% after 2000 cycles. This simple synthesis strategy for fabricating carbon anode materials with an excellent electrochemical performance should promote the development of green and large-scale energy storage devices.

The effects of seven mixing ratios (1:0, 3:1, 2:1, 1:1, 1:2, 1:3, and 0:1, swine manure (SM)/rice straw (RS), based on total solid) on anaerobic co-digestion (co-AD) of SM and RS mixtures were investigated in batch tests. The results showed that the highest methane yield (188.79 mL/g VSadded) was obtained at the ratio of 1:1, which was higher than that of the mono-digestion of RS or SM by 178.77% and 18.94%, respectively. For the remained six ratios, the methane yield increased with the increase of SM proportion. The highest organic matter degradation rates were also observed at the ratio of 1:1. The methane content of biogas and the pH, total alkalinity, and total ammonia nitrogen of the digestate all decreased with the increase of RS proportion and decrease of SM proportion. Additionally, the kinetic results of each anaerobic digestion (AD) step suggested that the co-AD of SM and RS at the ratio of 1:1 significantly improved the reaction rates of the four AD steps. Meanwhile, the methane production time was prolonged and the lag time of methanogenesis was shortened at the ratio of 1:1.

The development of carbon materials for potassium storage is limited by their low specific capacity and poor cycling stability due to the sluggish kinetics of K ions. Herein, fucoidan-derived oxygen-rich carbon nanosheets are reported as a fantastic anode for potassium ion batteries. Attributed to its 2D porous sheet-like structure (morphology engineering), rich oxygen doping (defect engineering), and dilated graphitic layer in an amorphous structure (structure engineering), a competitive capacity of 392 mA h g-1 at 0.05 A g-1 and a long cycling span over 2500 cycles at 2 A g-1 was achieved for the carbon anode, outperforming most of the reported carbons. The kinetic analyses reveal that rich active sites and a porous nanosheet structure account for the superb rate performance and cycling stability of the material. Ex situ X-ray photoelectron spectroscopy measurements demonstrate that the introduction of C[double bond, length as m-dash]O greatly promotes K+ adsorption, and that the improvement of the C[double bond, length as m-dash]O bonds during cycling contributes to enhancement in the capacity. The fabricated potassium ion hybrid capacitor displays an exceptional energy/power density of 193 W h kg-1/22 324 W kg-1, and a promising cycling stability with 99.3% capacity retention over 2000 cycles. This work provides a large-scale synthesis strategy for preparing oxygen-rich carbon nanosheets for advanced potassium ion storage.

ObjectiveTo characterize the status of ovarian reserve and ART outcomes in BPES women and provide informative reference for clinical diagnosis and treatment.MethodsTwenty-one women with BPES were screened for mutations in the FOXL2 gene and underwent assisted reproductive technology (ART) treatment. Indicators for ovarian reserve and ART outcomes were compared between patients with and without FOXL2 mutations. Additionally, ART outcomes were compared among patients with different subtypes of FOXL2 mutations.ResultsA total of 13 distinct heterozygous variants in the FOXL2 gene were identified in 80.95% of BPES women, including 4 novel mutations with plausible pathogenicity (c.173_175dup, c.481C>T, c.576del and c.675_714del). Compared to non-mutation group, patients with FOXL2 mutations had elevated levels of FSH (P=0.007), decreased AMH levels (P=0.012) and less AFC (P=0.015). They also had worse ART outcomes with large amount of Gn dosage (P=0.008), fewer oocytes (P=0.001), Day3 good quality embryos (P=0.001) and good quality blastocysts (P=0.037), and a higher cancellation rate (P=0.272). High heterogeneity of ART outcomes existed in BPES patients with different FOXL2 mutation types.ConclusionsBPES patients with FOXL2 mutations had diminished ovarian reserve and adverse ART outcomes. The genotype-reproductive phenotype correlations were highly heterogeneous and cannot be generalized. Genetic counseling for fertility planning and preimplantation or prenatal genetic diagnosis to reduce offspring inheritance are recommended.

Background: Triple-negative breast cancer (TNBC) is characterized by a more aggressive biological behavior and unfavorable outcome. Circulating and histological expression of THBS2 has been demonstrated to be a novel diagnostic and prognostic biomarker in patients with various types of tumors. However, few studies have evaluated the predictive and prognostic value of THBS2 in TNBC specifically.Methods: In total, 185 triple-negative breast cancer patients (TNBC) with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC and at surgery by enzyme-linked immunosorbent assay (ELISA). Histological THBS2 (hTHBS2) expression in patients with residual tumors was evaluated by immunohistochemistry (IHC) staining method. Correlations between variables and treatment response were studied. Kaplan-Meier plots and Cox proportional hazard regression model were applied for survival analysis. Functional activities of THBS2 in TNBC cells were determined by CCK-8 assay, colony formation, wound healing, and transwell assay.Results: Of the 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with a lower level of sTHBS2 at surgery and higher level of sTHBS2 change (OR = 0.88, 95%CI: 0.79–0.98, p = 0.020 and OR = 1.12, 95%CI: 1.02–1.23, p = 0.015, respectively). In survival analysis, hTHBS2 expression in residual tumor was of independent prognostic value for both disease-free survival (HR = 2.21, 95%CI = 1.24–3.94, p = 0.007) and overall survival (HR = 2.07, 95%CI = 1.09–3.92, p = 0.026). For functional studies, THBS2 was indicated to inhibit proliferation, migration, and invasion abilities of TNBC cells in vitro.Conclusion: Our findings confirmed the value of serum THBS2 level to predict pCR for TNBC patients and the prognostic performance of histological THBS2 expression in non-pCR responders after NAC. THBS2 might serve as a promising functional biomarker for patients with triple-negative breast cancer.

Transactional memory has been attracting increasing attention in recent years, and it provides optimistic concurrency control schemes for shared-memory parallel programs. The rapid development and wide adoption of transactional memory make this programming paradigm promising for achieving breakthroughs in massively parallel computing. There has been a large number of discussions towards transactional memory systems, which aimed at providing relatively simple and intuitive synchronization construction for shared-memory parallel programs without sacrificing performance. Hardware transactional memory (HTM) has become commercially available in mainstream processors, however, due to several inherent architectural limitations that will abort hardware transactions, such as cache overflows, context switches, hardware as well as software exceptions, etc., nowadays HTM systems come in a best-effort way, which necessitates the adoption of a software fallback path to ensure forward progress. In this paper, we survey state-of-the-art software-side optimizations for best-effort hardware transaction system, as well as several novel performance tuning techniques. Research efforts about joint usage of HTM and non-volatile memory (NVM) are also discussed.

A new fossil genus and species is described from the Middle Jurassic of China. The type of Sinoelcana minutagen. et sp. nov. has body and legs preserved. It is distinguished from all other elcanids by the unique combination of wing venation and stout ovipositor. The sickle-shaped ovipositor suggests that the new species had a preference for oviposition on plant material. A world key to the genera of Elcanidae is provided based on the wing venation.

Asthma is a complex and heterogeneous inflammatory response characterized by various immune cells, including myeloid-derived suppressor cells (MDSCs) and CD4+ T-cell subsets. However, few studies on MDSC subsets and the association between MDSCs and CD4+ T-cell subsets in asthma are reported. In the present study, we detected CD4+ T cells and MDSC subsets and evaluated the relationship of these cells in mice with ovalbumin-induced asthma. We found that asthmatic mice showed severe airway inflammatory response and inflammatory cell infiltration in the lungs and bronchoalveolar lavage fluid. We also noted increased numbers of Th2, Th17, and MDSCs; decreased proportion of Th1 and Treg cells in the splenocytes and lungs; and increased expression of pro-inflammatory cytokines in splenocytes and lungs. Granulocytic MDSCs (G-MDSCs) and Th17 cells were closely related. Gemcitabine treatment reduced the G-MDSC level and the iNOS expression, alleviated the inflammatory response, and decreased the proportion and number of Th2 and Th17 cells in asthmatic mice. Besides the increase in Th2 and Th17 cells, the findings indicate that G-MDSC elevation plays a crucial role in asthmatic mice.

Great progress has been made in the field of pedestrian detection, but the following two problems have not yet been well addressed. One problem is the missed detection of small scale pedestrain as false negative failure, and the other one is confusion with anthropomorphic negative samples like vertical structures as false positive failure. In this paper, to tackle the above two problems, we use the light-field camera to capture pedestrian images for the following reasons: (i) the light-field camera can obtain multi-depth refocused images in a single exposure using one sensor, (ii) compared with 2D images, these refocused images can provide different key representations for different parts of the image. We further establish a light-field pedestrian dataset with 1766 images for pedestrian detection. A multi-focus detection network proposed in this work consists of multiple-branch detection models and takes multiple refocused images as inputs. In order to select the appropriate candidate proposal bounding box as final detection results, we design a cumulative probability selection (CPS) layer to combine each refocused image branch and accumulate the probability of each candidate neighboring proposal. Experimental results demonstrate that the proposed method outperforms state-of-the-art methods on our light-field pedestrian dataset.

Background Potato (Solanum tuberosum) is the fourth most important food crop in the world and plays an important role in food security. Drought stress has a significantly negative impact on potato growth and production. There are several publications involved drought stress in potato, this research contributes to enrich the knowledge. Results In this study, next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing technology were used to study the transcription profiles in potato in response to 20%PEG6000 simulates drought stress. The leaves of the variety “Désirée” from in vitro plantlets after drought stress at six time points from 0 to 48 hours were used to perform NGS and SMRT sequencing. According to the sequencing data, a total of 12,798 differentially expressed genes (DEGs) were identified in six time points. The real-time (RT)-PCR results are significantly correlated with the sequencing data, confirming the accuracy of the sequencing data. Gene ontology and KEGG analysis show that these DEGs participate in response to drought stress through galactose metabolism, fatty acid metabolism, plant-pathogen interaction, glutathione metabolism and other pathways. Through the analysis of alternative splicing of 66,888 transcripts, the functional pathways of these transcripts were enriched, and 51,098 transcripts were newly discovered from alternative splicing events and 47,994 transcripts were functionally annotated. Moreover, 3445 lncRNAs were predicted and enrichment analysis of corresponding target genes was also performed. Additionally, Alternative polyadenylation was analyzed by TADIS, and 26,153 poly (A) sites from 13,010 genes were detected in the Iso-Seq data. Conclusion Our research greatly enhanced potato drought-induced gene annotations and provides transcriptome-wide insights into the molecular basis of potato drought resistance.

Background Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. Methods The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. Results Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). Conclusion This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.

Studies have shown that delayed initiation of surgery and adjuvant chemotherapy is associated with lower rates of breast cancer survival. However, it remains unclear whether delayed initiation of adjuvant hormone therapy (AHT) is associated with survival.To assess the association of time to adjuvant hormone therapy (TTH) with breast cancer survival and evaluate the factors associated with AHT.This cohort study examined data from the National Cancer Database from 2004 through 2014 to assess the association of TTH (stratified as ≤150 and150 days) with cancer survival. All patients included were diagnosed with stage I to stage III hormone receptor-positive, human epidermal growth factor receptor-2 (ERBB2; formerly HER2)-negative invasive breast cancer and underwent AHT without chemotherapy. Data were analyzed from April 2019 to May 2020.AHT was administered at different time points following surgical procedures for breast cancer treatment.An inverse probability of treatment weighting (IPTW) model was constructed to evaluate overall survival by adjusting for treatment facility, patient demographics, tumor characteristics, and treatment; multivariable logistic regression was conducted to assess factors associated with delayed treatment.A total of 144 103 patients (median [IQR] follow-up, 36.6 months [25.5-49.2 months]; mean [SD] age, 63.7 [11.6] years) were identified, which included 142 916 (99.2%) women, 11 574 (8.0%) Black patients, and 126 013 (87.4%) White patients. Of these, 134 873 patients (93.6%) had a TTH of 150 days or less and 9230 patients (6.4%) had a TTH longer than 150 days. The IPTW-based Cox model demonstrated that patients with delayed AHT (ie, a TTH past 150 days) were associated with decreased survival (hazard ratio [HR], 1.31; 95% CI, 1.26-1.35; P .001) compared with those receiving the timely treatment (TTH ≤150 days). Several sensitivity analyses (including IPTW with stabilized weight [HR, 1.31; 95% CI, 1.19-1.45; P .001], propensity score matching [HR, 1.41; 1.13-1.76; P = .002], and propensity score regression adjustment [HR, 1.29; 95% CI, 1.16-1.43; P .001]) and exploratory subgroup analyses yielded similar trends. Factors associated with delayed AHT included Black racial identity (OR, 1.66; 95% CI, 1.55-1.77), nonprivate insurance (eg, no insurance: OR, 1.46; 95% CI, 1.26-1.70), living in large metropolitan or metropolitan areas (reference vs urban, less urban, or rural: OR, 0.82; 95% CI, 0.76-0.87), treatment in a community hospital (reference vs academic or research: OR, 0.91; 95% CI, 0.84-0.98), Charlson-Deyo Comorbidity Index score 2 or higher (OR, 1.17; 95% CI, 1.04-1.32), poor grade differentiation (OR, 1.42; 95% CI, 1.32-1.53), II and III pathological stage (stage III: OR, 3.13; 95% CI, 2.76-3.54), estrogen receptor-positive (ER+)/progesterone receptor-negative (PR-) or ER-/PR+ (OR, 1.22; 95% CI, 1.13-1.31), receiving breast conservation surgery (reference vs mastectomy: OR, 0.87; 95% CI, 0.79-0.94), and radiotherapy (reference vs no radiotherapy: OR, 0.56; 95% CI, 0.52-0.61).The delay of the initiation of AHT past 150 days was associated with diminished survival in hormone receptor-positive, ERBB2-negative patients with breast cancer who did not receive chemotherapy. Efforts should be made to address factors associated with delayed treatment to improve survival.

Background: Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated.Methods: The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan–Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models.Results: Breast cancer (BC) patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR=1.433[95%CI 1.038-1.978], P=0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so that further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163-4.708], P=0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218-4.913], P=0.011).Conclusions: For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.

Background Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. Methods The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. Results CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. Conclusion Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.