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Abstract There are significant differences in distributed generators (DGs) distribution and load characteristics between different voltage levels, which makes it difficult to match sources and loads. We focus on the problem of different consumption capacities at different voltage levels and the divergence of interests among investment entities, and propose a coordinated planning model for DGs and soft open points (SOPs) based on the Stackelberg game. Firstly, a model of a multi‐voltage level distribution networks (DNs) is constructed based on SOPs. Next, the source‐load matching degree is proposed as a measure of the degree of matching between sources and loads in the DN, and the source‐load consumption rate is selected as an indicator to evaluate the impact of the load on DG consumption. Following this, the interest demands of DG investors and distribution company (DisCo) in multi‐voltage levels DN are analyzed, a planning mode based on the Stackelberg game is proposed, and this is solved by combining the genetic algorithm with second‐order cone programming. Finally, the effectiveness of the planning model is tested and verified using an improved IEEE 28‐node system. The results show that the proposed model improves the DG consumption capacity of DNs with multiple voltage levels while protecting the interests of DG investors and DisCo.

Abstract Land Use/Cover Change (LUCC) plays a crucial role in sustainable land management and regional planning. However, contemporary feature extraction approaches often prove inefficient at capturing critical data features, thereby complicating land cover categorization. In this research, we introduce a new feature extraction algorithm alongside a Segmented and Stratified Principal Component Analysis (SS-PCA) dimensionality reduction method based on correlation grouping. These methods are applied to UAV LiDAR and UAV HSI data collected from land use types (e.g., residential areas, agricultural lands) and specific species (e.g., tree species) in urban, agricultural, and natural environments to reflect the diversity of the study area and to demonstrate the ability of our methods to be applied in different classification scenarios. We utilize LiDAR and HSI data to extract 157 features, including intensity, height, Normalized Digital Surface Model (nDSM), spectral, texture, and index features, to identify the optimal feature subset. Subsequently, the best feature subset is inputted into a random forest classifier to classify the features. Our findings demonstrate that the SS-PCA method successfully enhances downscaled feature bands, reduces hyperspectral data noise, and improves classification accuracy (Overall Accuracy = 91.17%). Additionally, the CFW method effectively screens appropriate features, thereby increasing classification accuracy for LiDAR (Overall Accuracy = 78.10%), HIS (Overall Accuracy = 89.87%), and LiDAR + HIS (Overall Accuracy = 97.17%) data across various areas. Moreover, the integration of LiDAR and HSI data holds promise for significantly improving ground fine classification accuracy while mitigating issues such as the ‘salt and pepper noise’. Furthermore, among individual features, the LiDAR intensity feature emerges as critical for enhancing classification accuracy, while among single-class features, the HSI feature proves most influential in improving classification accuracy.

Abstract Objectives We explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC). Methods TRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types. Results A total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p

Abstract Objective Endometrial cancer is stepping into the era of precision therapy. Genomic test is recommended for newly diagnostic patients. However, outpatients displayed more complex characteristics. Here, we elucidated the clinical characteristics and genomic profiling of outpatients with endometrial cancer at our institution. Methods Between 2018 and 2023, 68 endometrial cancer received genomic tests at outpatient department of Fudan University Shanghai Cancer Center. Data, including age, pathological histology, FIGO stage and treatment strategy were collected. Germline mutations, molecular subtypes and other somatic mutations were also summarized. Results Overall, 72.1% (49/68) of patients receive genomic tests at primary diagnosis, while 27.9% (19/68) of patients received tests at recurrence. Nine patients had deleterious germline mutations, including BRCA1(2), MLH1(1), MSH2(2, including one with co-mutation of RAD50), MSH6(2), FANCA(1), MUTYH(1). Molecular subtypes were recognized among 62 patients, as POLE super-mutation(4, 6.5%), MSI-H(7, 11.3%), CN-Low(36, 58.1%) and CN-High(15, 24.2%). Ten patients received anti-PD1 monotherapy or in combination with chemotherapy or anti-angiogenic therapy, with the duration of disease control of 1 to 35 months. The ORR rate was 30%, and six patients had stable disease. The median (range) follow-up time was 18(2–160) months. 23(33.8%) relapses were recorded, and CN-High subtype displayed worst PFS compared with other subtypes (P

Large-scale outdoor point cloud registration is essential for the 3D reconstruction of outdoor scenes. Its central objective is to achieve accurate point cloud registration by determining accurate spatial transformation parameters. While feature-based methods eliminate the need for initial position estimation, they encounter challenges in handling high outlier rates. Therefore, a method capable of effectively managing outliers is crucial for enhancing the efficiency and accuracy of large-scale outdoor point cloud registration. This paper introduces the maximal clique with adaptive voting (MCAV) method, which leverages graph-based inlier compatibility to optimize potential matches. MCAV employs adaptive parameter voting (APV) to enhance computational efficiency, demonstrating significant speedup characteristics in datasets with a significant number of inliers. To further reduce outliers in potential matches, we integrate Black-Rangarajan Duality (BRD) and graduated non-convexity (GNC) into the truncated least squares (TLS) framework (BG-TLS). Accordingly, we propose the efficient BG-TLS (EBG-TLS) method for computing the registration model. Comparative analyses with traditional and deep learning-based methods across various real-world environments demonstrate that the proposed method outperforms existing algorithms in terms of rotation error, translation error, and efficiency, particularly in complex, high-noise settings. This method finds broad applications in geospatial mapping and surveying, autonomous navigation, and environmental monitoring.

Abstract Background Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories. Methods A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing. Results The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL. Conclusions This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

PURPOSEGenetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant.METHODSBetween 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2, other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays.RESULTSOverall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin.CONCLUSIONOur study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

In the realm of remote sensing, the vegetation index (VI) can bring out the subtleties and characteristics of a class of features or a specific feature and can indicate crop development, vegetation and non-vegetation, soil, and other related information. However, in the plateau region, due to characteristics such as plant type, soil type, and vegetation density, the currently available vegetation indices cannot properly extract vegetation information. Therefore, this study proposes a visible light vegetation index based on the visible band, the Improved-Red-Green-Blue Vegetation Index (IRGBVI), by analyzing the spectral characteristics of seven species of landforms in the visible light bands of the UAV in the plateau region, and applies this VI to compare the accuracy of vegetation information extraction with that of 13 VIs based on visible light bands. The investigation demonstrates that IRGBVI can successfully extract plant information with high accuracy in different regions of the plateau and can effectively eliminate the impacts of blue roofs and other factors in images. In conclusion, IRGBVI is a novel visible light vegetation index ideal for extracting vegetation information in plateau regions, and it has strong generalizability and reliability.

Abstract Background Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population. Methods We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients. Results The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p

Abstract To solve the problems of voltage violation and fast voltage fluctuation caused by photovoltaic (PV) grid connections in distribution networks, a two‐stage coordinated voltage control strategy for PV inverters with multimode coordinated operation in distribution networks (DNs) is proposed. It is based on the characteristics of PV inverters that can be regulated rapidly and continuously. First, the voltage control process is divided into two control stages according to the voltage change rate, and the corresponding voltage control models are established. Then, the operating modes of PV inverters are classified into three modes: economic prevention, economic control, and efficient control. Different operating modes are used to adapt to the two‐stage voltage control. Finally, a voltage fast control solution algorithm is proposed, which considers adaptive time delays and combines local measurement, prediction, and communication information to update control commands. The effectiveness and feasibility of the proposed voltage control strategy were demonstrated through simulation tests on a real 10‐kV line with a high PV penetration rate in the Anhui province of China. The results show that the proposed strategy can prevent voltage violation and sudden changes and can smooth out voltage fluctuation.

Abstract Background Neuroinflammatory factors, especially chemokines, have been widely reported to be involved in the pathogenesis of Alzheimer’s disease (AD). It is unclear how chemokines are altered in AD, and whether dysregulation of chemokines is the cause, or the consequence, of the disease. Methods We initially screened the transcriptomic profiles of chemokines from publicly available datasets of brain tissues of AD patients and mouse models. Expression alteration of chemokines in the blood from AD patients was also measured to explore whether any chemokine might be used as a potential biomarker for AD. We further analyzed the association between the coding variants of chemokine genes and genetic susceptibility of AD by targeted sequencing of a Han Chinese case–control cohort. Mendelian randomization (MR) was performed to infer the causal association of chemokine dysregulation with AD development. Results Three chemokine genes (CCL5, CXCL1, and CXCL16) were consistently upregulated in brain tissues from AD patients and the mouse models and were positively correlated with Aβ and tau pathology in AD mice. Peripheral blood mRNA expression of CXCL16 was upregulated in mild cognitive impairment (MCI) and AD patients, indicating the potential of CXCL16 as a biomarker for AD development. None of the coding variants within any chemokine gene conferred a genetic risk to AD. MR analysis confirmed a causal role of CCL5 dysregulation in AD mediated by trans-regulatory variants. Conclusions In summary, we have provided transcriptomic and genomic evidence supporting an active role of dysregulated CXCL16 and CCL5 during AD development.

Abstract Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis in both in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial–mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.

Abstract Clear cell carcinoma (CCC) of the abdominal wall is a rare and agressive disease. We aim to elucidate the clinical and prognostic characteristics of this disease. Medical records of ten patients diagnosed with CCC of the abdominal wall at Fudan University Shanghai Cancer Center were reviewed. We illustrate the clinical characteristics, treatment modality, and development of local recurrence or distant metastasis, as well as the survival outcome. The median (range) age of patients was 47 (39–61) years old. All patients had a history of cesarean section and abdominal wall endometriosis. All patients had primary surgery before referred to our center. Seven patients had only tumor resection, while two patients had lymph node metastasis at primary diagnosis. Four patients underwent supplementary surgery, and all postoperative pathology were negative. Genetic analyses had also been performed. The median (range) follow-up time was 20 (12–59) months. Local recurrence and lymph node metastasis were the most common recurrence types. The median (95% confidence interval) PFS was 11 (8.08–13.92) months. In summary, primary surgery should consider wide tumor resection and lymph node dissection. Adjuvant chemotherapy and radiotherapy should be recommended for potential benefits. More cases are still needed to elucidate the clinical management of this disease.

Abstract In order to reduce the impact of renewable energy output and load fluctuations and improve the flexibility of the integrated energy system (IES), it is necessary to further promote user participation in integrated demand response (IDR). Therefore, this paper constructs a hierarchical framework that enables the transaction of IDR resources among users by combining the information interaction network established by blockchain and the energy management network established by energy management system. This paper also analyses the comfort of users, the cost of energy purchase by users and the cost of energy use by load aggregators, and then develops a two‐layer optimization model. The results of the simulation show that the model and trading framework constructed in this paper can realize the trading of IDR resources among users, which effectively promotes the participation of users in IDR, reduces the cost of users and load aggregators, reduces the loss of IDR resources, enables more effective integration of dispersed IDR resources and improves the flexibility of IES.

In recent years, landslides occurred frequently in mountain and gorge areas, which brought serious threats to people's life and property safety. Most scholars use SAR single-track data for early identification of landslides in alpine and canyon areas, but some landslides cannot be identified due to geometric distortion of SAR imaging, and the identification results are not comprehensive. In order to carry out comprehensive and accurate early identification of landslide hazards in alpine valley area, this paper adopts bas-INSAR technology, takes the deep cut alpine valley area along the Xiaojiang River in Dongchuan as the research area, and adopts the combination of SAR data of lifting and lowering orbit to identify landslide hazards, and introduces high-resolution optical images as auxiliary identification. Finally, 18 landslide disaster bodies were identified, among which 5 were high-risk potential landslides, and three types of typical potential landslides were analyzed. The analysis results show that the use of elevator rail SAR data combined with complementary way, can effectively avoid the SAR single orbital data geometric distortion problem in mountain valley area, at the same time, this method can more accurately comprehensively to early identification of alpine valley area of landslide hazard, the cause of disaster prevention and mitigation and government decision-making provides a effective means.

Abstract Time‐of‐use (TOU) electricity prices are implemented based on the response characteristics of users. TOU prices guide the electricity consumption behaviour of users and make them actively respond to peak shaving and valley filling. In this paper, the conventional psychology response model of consumers is improved based on the history data of customer response to the TOU price. The paper defines four types of response load curves and proposes the response reliability indices. Additionally, it establishes the probability models of customer response. According to the characteristics of customer response, the sensitivity analysis of influencing factors and the risk analysis of customers are carried out according to the probability model of response. For instance, risk and characteristics analyses of the customer response were performed using the load data of residential areas in Nanjing city. The results indicate that the probability distribution of the customer response is approximate to the trapezoid distribution. The sequence of sensitivity coefficients of customer response factors is as follows: customer income, type of customer, and electrical equipment. The proposed method provides a scientific basis for electricity price implementers to accurately grasp the response behaviour of the user and establish a reasonable demand response strategy.

Abstract With the rapid development of carbon trading market, the volatility trend of carbon emission trading price (CETP) becomes one of the factors that cannot be ignored in energy system planning. Based on this, this paper proposes a multi‐objective expansion planning model for park‐level integrated energy system (PIES) that takes into account the volatility trend of CETP. First, the influencing factors of CETP prediction are filtered and downscaled, and a kernel extreme learning machine (KELM) model based on the improved multi‐objective grey wolf algorithm optimizer (IMOGWO) is used for probabilistic interval prediction of CETP. Next, the operational characteristics of each carbon emission device are analysed and a model for calculating the cost of carbon trading is proposed. Then, a two‐layer PIES planning model is developed with the objective of minimizing the annualized system cost and carbon emissions during the expansion planning cycle, the upper‐layer model is a planning model for solving equipment expansion scenarios, and the lower‐layer model is an operation model for calculating typical operation schemes. Finally, the simulation effect of the prediction model is verified by the European carbon trading data, and the planning schemes are compared and analysed to prove the effectiveness of the proposed method.

Aiming at the unreliability of historical data for short-term load forecasting caused by the sudden change of power grid load under emergencies, a short-term load prediction method adopting transfer learning is studied. The proposed transfer learning method combines the attention mechanism (AM) with the long short-term memory network coupled with input and forgetting gates (CIF-LSTM) to construct the AM-CIF-LSTM short-term load prediction model. First, the variational modal decomposition (VMD) method is used to extract the trend component and certain periodic high-frequency components of the load datasets of the scene to be predicted and similar scenes. Subsequently, the AM-encoder/decoder learning model is established based on the trend component, and the AM learnable parameters are trained and transferred to the AM-CIF-LSTM model. Furthermore, inspired by the idea of classified forecasting, the load trend component and periodic high-frequency components under the required prediction scene are predicted by AM-CIF-LSTM and deep recursive neural network (DRNN), respectively. Finally, the load forecasting results are superimposed to obtain the load forecasting value. The experimental results demonstrate that the proposed method outperformed the existing methods in multiple accuracy indicators and could predict the rapid change trend of load in the case of insufficient data accurately and stably.

Pathogenic mitochondrial DNA (mtDNA) mutations can cause a variety of human diseases. The recent development of genome-editing technologies to manipulate mtDNA, such as mitochondria-targeted DNA nucleases and base editors, offer a promising way for curing mitochondrial diseases caused by mtDNA mutations. The CRISPR-Cas9 system is a widely used tool for genome editing; however, its application in mtDNA editing is still under debate. In this study, we developed a mito-Cas9 system by adding the mitochondria-targeted sequences and 3′ untranslated region of nuclear-encoded mitochondrial genes upstream and downstream of the Cas9 gene, respectively. We confirmed that the mito-Cas9 system was transported into mitochondria and enabled knockin of exogenous single-stranded DNA oligonucleotides (ssODNs) into mtDNA based on proteinase and DNase protection assays. Successful knockin of exogenous ssODNs into mtDNA was further validated using polymerase chain reaction-free third-generation sequencing technology. We also demonstrated that RS-1, an agonist of RAD51, significantly increased knockin efficiency of the mito-Cas9 system. Collectively, we provide direct evidence that mtDNA can be edited using the CRISPR-Cas9 system. The mito-Cas9 system could be optimized as a promising approach for the treatment of mitochondrial diseases caused by pathogenic mtDNA mutations, especially those with homoplasmic mtDNA mutations.

ObjectiveThis study was aimed to profile hotspot exonuclease domain mutations (EDMs) of the DNA polymerase ϵ gene (POLE) in endometrial cancer (EC) and to investigate the effects of EDMs on tumor cell behavior and catalytic activities of Polϵ.MethodsPOLE sequencing was performed in tumor tissue samples from patients with EC to identify hotspot EDMs. Bioinformatics tools were used to select the potential pathogenic EDMs. The association of EDMs with the clinical outcomes of patients was assessed. EC cells were transfected with wildtype POLE or POLE variants to examine the effects of the EDMs on EC cell behavior, including cell cycle, migration, and invasion. Co-immunoprecipitation was employed to obtain FLAG-tagged wildtype and mutant catalytic subunits of Polϵ, followed by the assessment of polymerase and exonuclease activities.ResultsIn addition to previously reported P286R and V411L, R375Q and P452L were identified as novel, and deleterious POLE hotspot EDMs of EC. Patients in EDM group had significantly better clinical outcomes than the rest of the cohort. Compared with wildtype POLE, overexpression of POLE variants promoted cisplatin resistance, G0/G1 cell cycle arrest, and cell migration and invasion in EC cells. Overexpression of POLE variants significantly increased the abundance of 3’-OH and upregulated the expression of DNA mismatch repair genes in HEK293T cells. Compared with wildtype Polϵ, Pol ϵ mutants exhibited undermined polymerase and exonuclease abilities in the presence of mismatched nucleotides in HEK293 cells.ConclusionWe characterized the of hotspot exonuclease domain mutations in the DNA polymerase ϵ gene and identified P286R, V411L, R375Q, and P452L as pathogenic POLE hotspot EDMs in endometrial cancer. These hotspot EDMs are associated with the malignant behavior of endometrial cancer cells in vitro and favorable prognosis in patients, suggesting that POLE affects a wide range of cellular processes beyond DNA replication and proofreading.

Abstract LncRNAs play an important role in tumorigenesis and progression; however, the function and mechanisms of lncRNAs in esophageal cancer (EC) remain largely unclear. In this study, we screened the differentially expressed lncRNAs in EC by using RNA-seq and one of the most upregulated lncRNAs, lncRNA RP11-465B22.8, was further characterized. LncRNA RP11-465B22.8 was upregulated in EC tissues and high lncRNA RP11-465B22.8 expression was associated with poor survival of EC patients. Ectopic expression of lncRNA RP11-465B22.8 enhanced the proliferation, migration, and invasion of EC cells, whereas knockdown of lncRNA RP11-465B22.8 led to the opposite effects. Mechanistically, lncRNA RP11-465B22.8 sponged miR-765 to increase the expression of KLK4. Moreover, LncRNA RP11-465B22.8 could be delivered from EC cells to macrophages via exosomes and subsequently induced M2 macrophage-induced cell migration and invasion. Our findings revealed a novel lncRNA RP11-465B22.8/miR-765/KLK4 pathway in EC and indicated that lncRNA RP11-465B22.8 might be a potential target for EC therapy.

Abstract Alzheimer’s disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-β (Aβ) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including APP, PSEN1, and PSEN2 impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aβ pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.

Taking the debris flow gully of the tributary of the Dabaini River on the left bank of the middle reaches of the Xiaojiang River Basin in Dongchuan District, Yunnan Province as the research object, the surface landform data of the debris flow gully was collected by Unmanned Aerial Vehicle (UAV) remote sensing technology. This paper proposes a method of extracting the control points of the same-named objects in combination with the ground three-dimensional laser scanning modeling data to realize the absolute orientation of UAV image data. Through Smart3D image data processing, a three-dimensional terrain model of the study area is constructed to obtain digital orthophoto map (DOM), digital surface model (DSM) and high-density matching point cloud. The point cloud data is processed using the Irregular Triangle Network progressive encryption technology in PhotoScan software to obtain a digital elevation model (DEM) with a resolution of 0.5 m. Combined with the relevant terrain analysis modules in ArcGIS and Cloud Compare, the terrain characteristics of this section of debris flow valley area can be analyzed. The technical route and method used in the modeling and analysis of debris flow gully terrain based on UAV remote sensing are of important empirical case reference value and practical guiding significance for qualitative and quantitative detection of geological disasters in the plateau complex mountain area and their monitoring and prevention.

Abstract Background Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. Methods A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. Results dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). Conclusions Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

ObjectiveTo examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment.MethodsPrimary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram.ResultsA total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075–0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151–3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317–0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838–7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325–2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS.ConclusionsPrimary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype.

As UAV technology has been leaping forward, small consumer-grade UAVs equipped with optical sensors are capable of easily acquiring high-resolution images, which show bright prospects in a wide variety of terrains and different fields. First, the crater rim landscape of the Dinosaur Valley ring formation located on the central Yunnan Plateau served as the object of the surface change detection experiment, and two repetitive UAV ground observations of the study area were performed at the same altitude of 180 m with DJI Phantom 4 RTK in the rainy season (P1) and the dry season (P2). Subsequently, the UAV-SfM digital three-dimensional (3D) modeling method was adopted to build digital models of the study area at two points in time, which comprised the Digital Surface Model (DSM), Digital Orthomosaic Model (DOM), and Dense Image Matching (DIM) point cloud. Lastly, a quantitative analysis of the surface changes at the pit edge was performed using the point-surface-body surface morphological characterization method based on the digital model. As indicated by the results, (1) the elevation detection of the corresponding check points of the two DSM periods yielded a maximum positive difference of 0.2650 m and a maximum negative value of −0.2279 m in the first period, as well as a maximum positive difference of 0.2470 m and a maximum negative value of −0.2589 m in the second period. (2) In the change detection of the two DOM periods, the vegetation was 9.99% higher in the wet season than in the dry season in terms of coverage, whereas the bare soil was 10.54% more covered than the wet season. (3) In general, the M3C2-PM distances of the P1 point cloud and the P2 point cloud were concentrated in the interval (−0.2,0.2), whereas the percentage of the interval (−0.1,0) accounted for 26.69% of all intervals. The numerical model of UAV-SfM was employed for comprehensive change detection analysis. As revealed by the result of the point elevation difference in the constant area, the technique can conform to the requirements of earth observation with certain accuracy. The change area suggested that the test area can be affected by natural conditions to a certain extent, such that the multi-source data can be integrated to conduct more comprehensive detection analysis.

BackgroundLimited data exist for adults with recurrent pectus excavatum (PE) treated with minimally invasive surgical repair.MethodsBetween July 2008 and December 2020, forty-two adult patients with recurrent PE underwent a modified Nuss procedure with a newly designed bar in our center. A small vertical subxiphoid incision was used to separate severe adhesions when necessary. Multiple steel wires were sutured, and the rib space was narrowed to firmly fix the bar. The primary end point was Haller index change after operation. The secondary end points included length of stay after operation, short-term and long-term complications.ResultsThe mean patient age was 22.02 ± 3.49 years. The mean Haller index was 4.59 ± 1.09. A subxiphoid incision was performed in 12 patients. Thirty-nine patients had one bar placed, and 3 patients required two bars. Sixteen patients had 3 or more wires fixation, and 4 patients needed to have their intercostal space narrowed. There was no perioperative death, and the mean hospitalization was 5.57 ± 2.47 days. The Haller index reduced to 3.03 ± 0.41 after the operation (t = 11.85, p < 0.001). During the follow-up, there were 3 patients who developed non-infective wound effusion; bar rotations occurred in 3 patients. Twenty patients had the bar removed, post-bar removal Haller index was significantly reduced compared to the preoperative Haller index (2.89 ± 0.37 vs. 4.72 ± 1.05, t = 8.96, p < 0.001).ConclusionsThe modified Nuss procedure with a new titanium alloy bar can achieve good results for adult patients with recurrent PE.

Unmanned aerial vehicles (UAVs) and light detection and ranging (LiDAR) can be used to analyze the geomorphic features in complex plateau mountains. Accordingly, a UAV–LiDAR system was adopted in this study to acquire images and lidar point-cloud dataset in the annular structure of Lufeng, Yunnan. A three-dimensional (3D) model was constructed based on structure from motion and multi-view stereo (SfM–MVS) in combination with a high-resolution digital elevation model (DEM). Geomorphic identification, measurement, and analysis were conducted using integrated visual interpretation, DEM visualization, and geographic information system (GIS) topographic feature extraction. The results indicated that the 3D geomorphological visualization and mapping were based on DEM, which was employed to identify the dividing lines and ridges that were delineated of the pit rim structure. The high-resolution DEM retained more geomorphic detail information, and the topography and the variation between ridges were analyzed in depth. The catchment and ponding areas were analyzed using accurate morphological parameters through a multi-angle 3D visualization. The slope, aspect, and topographic wetness index (TWI) parameters were analyzed through mathematical statistics to qualitatively and accurately analyze the differences between different ridges. This study highlighted the significance of the UAV–LiDAR high-resolution topographic measurements and the SfM–MVS 3D scene modelling in accurately identifying geomorphological features and conducting refined analysis. An effective framework was established to acquire high-precision topographic datasets and to analyze geomorphological features in complex mountain areas, which was beneficial in deepening the research on numerical simulation analysis of geomorphological features and reveal the process evolution mechanism.

Abstract Background Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker‐guided immune combination therapy of OvCa in the future. Methods Whole‐exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune‐related genes and the abundance of tumor‐infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next‐generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB). Results A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR‐deficient tumors. Conclusions DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker‐guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy.

Lung cancer: Targeting a vicious circle Therapies targeting a molecular feedback loop involved in tumor growth may prove valuable for treating non-small-cell lung cancer. Fangbao Ding, Jianbing Huang, and co-workers at Shanghai Jiao Tong University in Shanghai, China, have shown how an enzyme called USP21 promotes cancer cell proliferation and tumor growth in non-small-cell lung cancer. The team took cancerous and non-cancerous lung tissue samples from 42 patients, and analyzed the expression and behavior of USP21. The enzyme was highly expressed in cancerous tissues, where it stabilized a known gene with the potential to cause cancer called YY1. This gene also regulated the expression of a particular RNA molecule, which in turn worked to increase levels of USP21. This cyclical process encouraged the proliferation, migration and invasion of non-small-cell lung cancer cells, and may provide a future therapeutic target.

Little is known about the genetics of sclerosing stromal tumor of the ovary, a rare type of sex cord-stromal tumor. Here, the authors use sequencing strategies to show that in a cohort of 26 tumor samples 65% carry a FHL2-GLI2 fusion gene and demonstrate in vitro that the fusion gene has oncogenic properties.

Abstract Background Ovarian metastatic tumors from lung adenocarcinoma are rare, and a serial study of these tumors is lacking to date. Additionally, a better understanding of the clinicopathological and molecular characteristics of metastatic tumors is needed. Methods Seven cases of ovarian metastasis from lung adenocarcinoma from 2013 to 2017 at our institute were investigated. The results were combined with those found in literature review. A total of 16 cases were analyzed in the present study. We examined clinicopathological and immunohistochemical characteristics, further detected ALK rearrangement by FISH (fluorescence in situ hybridization), and assessed EGFR and KRAS mutations using Sanger sequencing or the amplification refractory mutation system (ARMS). Results The mean age of the patients was 44.6 years (range, 33–56 years). Eleven of sixteen patients developed ovarian tumors within a mean time of 18.5 months (range, 5–48 months) from the initial diagnosis of lung adenocarcinoma; 5 patients had lung tumors and ovarian masses simultaneously. Five tumors (5/16, 31%) occurred in the bilateral ovaries, and the others were unilateral ovarian tumors (11/16, 69%). All seven cases from our institute were positive for TTF-1 and Napsin A but negative for PAX8. In four cases, ALK (D5F3) was diffusely and strongly expressed, with ALK rearrangements (4/7, 57%). Overall, ALK rearrangement was found by FISH or immunohistochemistry in 11/16 (69%) cases. In two cases, EGFR mutations in exons 19 and 21, respectively, were found. One patient did not detected EGFR or ALK mutation in the metastatic tumor, but the primary lung adenocarcinoma did harbor an EGFR mutation. Two cases had no alterations in three genes above. Although the mean survival time of the patients with ALK rearrangement was longer than those without (mean survival time 25 m vs. 20 m), no statistical significance of the difference was found. Conclusions As the largest case series of ovarian metastasis from lung adenocarcinoma, our findings indicate that ALK rearrangement is the most common molecular alteration. Although patients with ALK rearrangement appear to have a better prognosis than do those without ALK rearrangement, more cases with longer follow-up and multivariant analysis are needed to clarify this point.

Background: Schizophrenia is a complex mental disorder resulting in poor life quality and high social and economic burden. Despite the fact that genome-wide association studies (GWASs) have successfully identified a number of risk loci for schizophrenia, identifying the causal genes at the risk loci and elucidating their roles in disease pathogenesis remain major challenges. Methods: The summary data-based Mendelian randomization analysis (SMR) was used to integrate a large-scale GWAS of schizophrenia with brain expression quantitative trait loci (eQTL) data and brain methylation expression quantitative trait loci (meQTL) data, to identify novel risk gene(s) for schizophrenia. We then analyzed the mRNA expression and methylation statuses of the gene hit BTN3A2 during the early brain development. Electrophysiological analyses of CA1 pyramidal neurons were performed to evaluate the excitatory and inhibitory synaptic activity after overexpression of BTN3A2 in rat hippocampal slices. Cell surface binding assay was used to test the interaction of BTN3A2 and neurexins. Findings: We identified BTN3A2 as a potential risk gene for schizophrenia. The mRNA expression and methylation data showed that BTN3A2 expression in human brain is highest post-natally. Further electrophysiological analyses of rat hippocampal slices showed that BTN3A2 overexpression specifically suppressed the excitatory synaptic activity onto CA1 pyramidal neurons, most likely through its interaction with the presynaptic adhesion molecule neurexins. Interpretation: Increased expression of BTN3A2 might confer risk for schizophrenia by altering excitatory synaptic function. Our result constitutes a paradigm for distilling risk gene using an integrative analysis and functional characterization in the post-GWAS era. Fund: This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), the National Natural Science Foundation of China (31730037 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY). Keywords: Schizophrenia, Integrative analysis, BTN3A2, Brain development, Glutamatergic synapse

Doublecortin (DCX) is transiently expressed in new-born neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) related to adult neurogenesis in the olfactory bulb (OB) and hippocampal formation. DCX immunoreactive (DCX+) immature neurons also occur in the cerebral cortex primarily over layer II and the amygdala around the paralaminar nucleus (PLN) in various mammals, with interspecies differences pointing to phylogenic variation. The tree shrews (Tupaia belangeri) are phylogenetically closer to primates than to rodents. Little is known about DCX+ neurons in the brain of this species. In the present study, we characterized DCX immunoreactivity (IR) in the forebrain of Chinese tree shrews aged from 2 months- to 6 years-old (n = 18). DCX+ cells were present in the OB, SVZ, SGZ, the piriform cortex over layer II, and the amygdala around the PLN. The numerical densities of DCX+ neurons were reduced in all above neuroanatomical regions with age, particularly dramatic in the DG in the 5–6 years-old animals. Thus, DCX+ neurons are present in the two established neurogenic sites (SVZ and SGZ) in the Chinese tree shrew as seen in other mammals. DCX+ cortical neurons in this animal exhibit a topographic pattern comparable to that in mice and rats, while these immature neurons are also present in the amygdala, concentrating around the PLN as seen in primates and some nonprimate mammals.

We present a case of primary yolk sac tumor of the endometrium. This rare tumor occurred in a 43-year-old woman with a pure primary yolk sac tumor. The tumor resembled yolk sac tumor morphology of the ovary. Tumor cells expressed SALL4, AFP, GPC-3, and AE1/AE3 and were focal positive for PAX8. EMA, ER, and PR, among others, were negative. We further analyzed 29 reported cases of this rare tumor in the literature. In total, 17 of 30 patients (57%) had pure endometrial yolk sac tumor, and 13 (43%) had a concomitant somatic neoplasm (endometrial adenocarcinoma was the most common). Although the average age was 52 years (range: 24–87 years), patients with pure yolk sac tumor were younger than those with concomitant somatic tumors, with a mean age of 44.41 years (24–68 years) versus 61.92 years (28–87 years), P = 0.008. Patients with endometrial yolk sac tumor combined with somatic tumor tend to have a slightly higher stage and a poor prognosis.

This work aimed to detect the vegetation coverage and evaluate the benefits of afforestation and ecological protection. Unmanned aerial vehicle (UAV) aerial survey was adopted to obtain the images of tailings area at Ma’anshan near the Dianchi Lake estuary, so as to construct a high-resolution Digital Orthophoto Map (DOM) and high-density Dense Image Matching (DIM) point cloud. Firstly, the optimal scale was selected for segmentation by considering the terrain. Secondly, the visible-band difference vegetation index (VDVI) of the classified vegetation information of the tail mining area was determined from the index gray histogram, ground class error analysis, and the qualitative and quantitative analysis of the bimodal index. Then, the vegetation information was extracted by combining the random forest (RF) classification algorithm. Finally, the extracted two-dimensional (2D) vegetation information was mapped to the three-dimensional (3D) point cloud, and the redundant data was eliminated. Fractional vegetation cover (FVC) was counted in the way of surface to point and human–machine combination. The experimental results showed that the vegetation information extracted from the 2D image was mapped to the 3D point cloud in the form of surface to point, and the redundant bare ground information was eliminated. The statistical FVC was 36.06%. The field survey suggested that the vegetation information in the turf dam area adjacent to the open phosphate deposit accumulation area research area was sparse. Relevant measures should be taken in the subsequent mining to avoid ecological damage caused by expanded phosphate mining. In general, applying UAV measurement technology and related 2D and 3D products to detect the vegetation coverage in an open phosphate mine area was of practical significance and unique technical advantages.

ObjectiveTo compare survival between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for the treatment of ovarian cancer patients per our selective protocol.MethodsBetween Sep 1st, 2015, and Aug 31st, 2017, 161 patients were enrolled in our prospective cohort. All of the patients received preoperative clinic-radiological assessments, according to the Suidan criteria for R0 resection. Patients with a score of 0–2 received PDS. Patients with a score of ≥3 were counseled on the choices of PDS, NACT, or an optional staging laparoscopy, according to the Fagotti criteria. Clinic-pathological data were prospectively collected until May 1st, 2020, and the impacts of different treatment strategies on progression-free survival (PFS) and overall survival (OS) were analyzed.Results110 patients underwent PDS, and 51 patients received NACT with consequent interval debulking surgery. The R0 resection rate was 57.8%. All but one of the patients received platinum-based chemotherapy, and 105 (65.2%) patients were platinum-sensitive. Based on the univariate analysis, the PDS group exhibited prolonged PFS compared with the NACT group (P=0.029). The subgroup analysis showed that patients receiving NACT with residual disease (RD) exhibited the worst PFS (P=0.001). Based on the multivariate analysis, NACT with RD was still an independent impaired factor for PFS (P=0.04). However, NACT did not affect OS in the univariate or multivariate analyses.ConclusionIn our prospective cohort, NACT ovarian patients exhibited inferior PFS and noninferior OS compared with PDS patients. Given our selective protocol, NACT cannot be arbitrarily denied while appropriate PDS is still a priority.

The nonlinear characteristics of wind power series and random fluctuation characteristics of wind resources have a harmful effect on stability of wind power prediction. This paper proposes a novel hybrid wind power short-term prediction model for improving precision and stability of wind power prediction. Firstly, the non-stationary wind power time series is decomposed by complete ensemble empirical mode decomposition - Lempel-Ziv complexity (CEEMD-LZC). Secondly, local linear embedding (LLE) is used to reduce the dimension of meteorological data with maintaining the essential structure of meteorological data. The integrated meteorological data predigested by LLE are treated as input of the prediction model. Finally, ant lion optimization (ALO) is utilized to optimize the weights and biases of extreme learning machine (ELM) network nodes to improve ELM prediction performance. The results of case studies show that the proposed model has a good forecasting effect and is more advantageous in 48h-ahead wind power forecasting.

The Chinese tree shrew (Tupaia belangeri chinensis) has the potential to replace the use of non-human primates in biomedical research. To increase the availability of this species, we have undertaken the ambitious task of establishing inbred lines of the Chinese tree shrew; however, we have been hindered by a low survival rate of inbred pups. Here, we report our artificial rearing (AR) of Chinese tree shrew pups using four different milk substitutes: the formula described by Tsang and Collins (milk TC) and three commercially available milk substitutes intended for possums (milk A and milk C) and for guinea pigs (milk B). We compared the effects of these milk substitutes and maternal milk on the daily milk consumption, growth performance, and survival of the pups. We also assessed the life span and reproductive performance of the F1 individuals given the best milk substitute as compared to the maternally reared (MR) pups. Milk B was found to be appropriate for AR. Pups fed with milk B had a high survival rate at the weaning age compared to those fed with the other milk substitutes. The AR pups fed with milk B had a life span similar to that of MR pups. AR females fed with milk B had an earlier age of the first reproduction, a larger number of litters, and a higher rate of survival of the offspring at the weaning age compared with the MR females. The successful optimization of a milk substitute for AR of Chinese tree shrew pups will undoubtedly facilitate the wide usage of this experimental animal.

Abstract Background The aim of our study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), was associated with clinical characteristics and prognosis in patients with high-grade serous ovarian cancer (HGSC). Methods We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. Preoperative PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count (per mm3). The optimal PNI cutoff value for overall survival (OS) was identified using the online tool “Cutoff Finder”. Clinical characteristics and PNI were compared with chi-square or Fisher’s exact tests, as appropriate. The impact of PNI on OS was analyzed using the Kaplan–Meier method and Cox proportional hazards model. Results The median (range) PNI was 46.2 (29.2–67.7). The 45.45 cutoff value discriminated patients into the high-PNI and low-PNI groups. A low preoperative PNI was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, residual disease and platinum resistance. For univariate analyses, a high PNI was associated with increased OS (p

Granular cell tumors (GCTs) are rare tumors that arise in multiple anatomical locations. Here, the authors investigate the genomics of GCTs, finding inactivating somatic mutations in ATP6AP1 or ATP6AP2 in 72% of the 82 GCTs analyzed. In vitro manipulation of these genes recapitulated GCT phenotypes in cellular models.

Abstract Background Programmed cell death ligand 1 (PD-L1) is a potential predictive biomarker of the response to anti-PD-L1/anti- programmed cell death 1 (PD-1) therapy in multiple cancers, including triple negative breast cancer(TNBC). The purpose of this study was to investigate whether PD-L1 expression is homogenous in primary tumors(PTs) and synchronous axillary lymph node metastases(LNMs) of TNBC. Methods PD-L1 expression was immunohistochemically evaluated in 101 TNBC patients’ PTs and paired LNMs. PD-L1 expression in tumor cells and infiltrating immune cells or node lymphocytes in the PTs and associated LNMs was scored separately and was correlated with patients’ clinical parameters and prognoses. Results PD-L1 expression exhibited spatial heterogeneity in both the tumor cells and the infiltrating immune cells or node lymphocytes of PTs and LNMs. The PD-L1 expression levels were significantly higher in the lymphocytes and tumor cells of the LNMs than in the PTs. PD-L1 expression was also more frequent among the LNMs. PD-L1 expression was associated with high grade and more stromal tumor-infiltrating lymphocytes(TILs). Furthermore, the disease-free survival and overall survival were similar between the PT- negative/LNM- positive and PT- positive/LNM- positive patients, both of which exhibited worse disease-free survival(DFS) thanPT -negative/LNM -negative patients. Conclusions The differential expression of PD-L1 between the PTs and LNMs suggests that LNMs PD-L1 status may be used to indicate whether PD-1/PD-L1-targeted therapy would be suitable for a node-positive TNBC patient in the future.

Unmanned Aerial Vehicles (UAVs) are a novel technology for landform investigations, monitoring, as well as evolution analyses of long−term repeated observation. However, impacted by the sophisticated topographic environment, fluctuating terrain and incomplete field observations, significant differences have been found between 3D measurement accuracy and the Digital Surface Model (DSM). In this study, the DJI Phantom 4 RTK UAV was adopted to capture images of complex pit-rim landforms with significant elevation undulations. A repeated observation data acquisition scheme was proposed for a small amount of oblique-view imaging, while an ortho-view observation was conducted. Subsequently, the 3D scenes and DSMs were formed by employing Structure from Motion (SfM) and Multi-View Stereo (MVS) algorithms. Moreover, a comparison and 3D measurement accuracy analysis were conducted based on the internal and external precision by exploiting checkpoint and DSM of Difference (DoD) error analysis methods. As indicated by the results, the 3D scene plane for two imaging types could reach an accuracy of centimeters, whereas the elevation accuracy of the orthophoto dataset alone could only reach the decimeters (0.3049 m). However, only 6.30% of the total image number of oblique images was required to improve the elevation accuracy by one order of magnitude (0.0942 m). (2) An insignificant variation in internal accuracy was reported in oblique imaging-assisted datasets. In particular, SfM-MVS technology exhibited high reproducibility for repeated observations. By changing the number and position of oblique images, the external precision was able to increase effectively, the elevation error distribution was improved to become more concentrated and stable. Accordingly, a repeated observation method only including a few oblique images has been proposed and demonstrated in this study, which could optimize the elevation and improve the accuracy. The research results could provide practical and effective technology reference strategies for geomorphological surveys and repeated observation analyses in sophisticated mountain environments.

Abstract Background Mounting evidence has shown that KRAS and BRAF are somatic mutations associated with low grade serous carcinoma (LGSC) of the ovary. However, the frequency of KRAS or BRAF mutation was variable in literatures, with a frequency of 16–54% for KRAS mutation and 2–33% for BRAF mutation. Meanwhile, the prognostic significance of KRAS or BRAF mutation remains controversial. Methods Codons 12 and 13 of exon 2 of KRAS gene and exon 15 of BRAF gene were analyzed using direct Sanger sequencing in 32 cases of LGSC of the ovary. The associations between KRAS or BRAF mutation and clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) were statistically analyzed. Results KRAS mutation was observed in nine cases (9/32, 28%) and BRAF mutation in two cases (2/32, 6%). KRAS and BRAF mutations were mutually exclusive. Neither KRAS nor BRAF mutation was statistically associated with OS or DFS in our cohort, although there was a favorable prognostic trend in patients with KRAS G12D mutation than those with KRAS G12 V mutation or wild-type KRAS for OS. Conclusions The present study indicated a low frequency of BRAF or KRAS mutation in Chinese patients with LGSC of the ovary, and neither KRAS nor BRAF mutation is a prognostic factor.

With the wide application of distributed generation (DG) and the rapid development of alternating current/direct current (AC/DC) hybrid microgrids, the optimal planning of distributed generation connecting to AC/DC distribution networks/microgrids has become an urgent problem to resolve. This paper presents a collaborative planning method for distributed generation access to AC/DC distribution (micro) grids. Based on the grid structure of the AC/DC distribution network, the typical interconnection structure of the AC/DC hybrid microgrid and AC/DC distribution network is designed. The optimal allocation models of distributed power supply for the AC/DC distribution network and microgrid are established based on analytical target cascading. The power interaction between the distribution network and microgrid is used to establish a coupling relationship, and the augmented Lagrangian penalty function is used to solve the collaborative programming problem. The results of distributed power supply allocation are obtained, solving the problem so that distribution generation with different capacity levels is connected to the power grid system in a single form.

Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients' clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS.

With the rapid development of AC/DC hybrid microgrids and the widespread use of distributed power resources, planning strategies for microgrids with high-density distributed power generation have become an urgent problem. Because current research on microgrid planning has not considered line factors, this paper analyses the planning of an AC/DC hybrid microgrid based on an AC microgrid. The capacity and siting of the distributed power resources are optimized, taking into account the influence of the line investment cost and the interactive power upper limit on the planning results. In the proposed model, the objective is aimed at minimizing the sum of investment cost, load-loss economic cost, and system losses, taking into consideration power balance constraints and feeder number constraints. The commercial solver CPLEX is applied to attain the optimal distributed power capacity and site. The theoretical results are verified by an actual system.

BACKGROUND:Ki67 labeling index (LI) is critical for treatment options and prognosis evaluation in breast cancer. Visual assessment (VA) is widely used to assess Ki67 LI, but has some limitations. In this study, we compared the consistency between VA and automated digital image analysis (DIA) of Ki67 LI in breast cancer, and to evaluate the application value of DIA in Ki67 LI assessment. METHODS:Ki67 immunostained slides of 155 cases of primary invasive breast cancer were eyeballing assessed by five breast pathologists and automated digital image analyzed by one breast pathologist respectively. Two score methods, hot-spot score and average score, were used to choose score areas. The intra-class correlation coefficient (ICC) was used to analyze the consistency between VA and DIA, and Wilcoxon signed-rank test was used to compare the median of paired-difference between VA and DIA values. RESULTS:(1) A perfect agreement was demonstrated between VA and DIA of Ki67 LI by ICC analysis (P30% Ki67 LI). The concordance was relatively lower in intermediate Ki67 LI group (11%-30%) compared with high (>30%) Ki67 LI groups according to both methods. (3) All cases were classified into three groups by paired-difference (d) between VA values of hot-spot score and average score (d