Miracle-dz/UniFAR-FTUs huggingface dataset:
CD103+ Tissue Resident T-Lymphocytes Accumulate in Lung Metastases and Are Correlated with Poor Prognosis in ccRCC

Simple Summary Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor, with highly heterogeneous responses to immune checkpoint inhibition therapy. The role of immune cells infiltrating distant metastases and their impact on prognosis and response to immunotherapy are still unclear. To elucidate the prognostic value of immune cell subtypes, we analyzed the immune cell infiltrate in ccRCC primary tumors and paired distant metastases. We hypothesized that specific subtypes of immune cells may be involved in the control of metastases and may have an impact on the prognosis of ccRCC. Abstract Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor with variable responses to immune checkpoint therapy. The significance of the immune cell infiltrate in distant metastases, their association with the immune infiltrate in the primary tumors and their impact on prognosis are poorly described. We hypothesized that specific subtypes of immune cells may be involved in the control of metastases and may have an impact on the prognosis of ccRCC. We analyzed the immune microenvironment in ccRCC primary tumors with distant metastases, paired distant metastases and non-metastasized ccRCC (n = 25 each group) by immunohistochemistry. Confirmatory analyses for CD8+ and CD103+ cells were performed in a large ccRCC cohort (n = 241) using a TCGA-KIRC data set (ITGAE/CD103). High immune cell infiltration in primary ccRCC tumors was significantly correlated with the development of distant tumor metastasis (p < 0.05). A high density of CD103+ cells in ccRCC was more frequent in poorly differentiated tumors (p < 0.001). ccRCCs showed high levels of ITGAE/CD103 compared with adjacent non-neoplastic tissue. A higher density of CD103+ cells and a higher ITGAE/CD103 expression were significantly correlated with poor overall survival in ccRCC (log rank p < 0.05). Our results show a major prognostic value of the immune pattern, in particular CD103+ cell infiltration in ccRCC, and highlight the importance of the tumor immune microenvironment.
Impact of Regorafenib on Endothelial Transdifferentiation of Glioblastoma Stem-like Cells

Simple Summary Glioblastomas (GBM) are the most frequent and aggressive adult brain tumours with a poor prognosis despite heavy therapy that combines surgical resection and radio-chemotherapy. There is a real therapeutic failure concerning these tumours and it highlights the need for new efficient and usable molecules in these particular and not easily reachable cancers. GBM are also characterised by abnormal and abundant vascularisation, of which some vessels originate from transdifferentiation of GBM stem cells (GSC) to tumour-derived endothelial cells (TDEC). As this mechanism was described as essential for tumour growth, we evaluated the impact of regorafenib, a multikinase inhibitor with anti-angiogenic and anti-tumourigenic activity on transdifferentiation but also directly on GSC. Regorafenib significantly decreases GSC proliferation in vitro but also in vivo. Regorafenib also inhibits transdifferentiation by decreasing phenotypic and functional endothelial features of TDEC obtained from non-irradiated GSC but also of TDEC obtained from irradiated GSC. All these results confirm that regorafenib clearly impacts GSC tumour formation and transdifferentiation and may therefore be a promising therapeutic option in combination with chemo/radiotherapy for the treatment of these highly aggressive brain tumours. Abstract Glioblastomas (GBM) are aggressive brain tumours with a poor prognosis despite heavy therapy that combines surgical resection and radio-chemotherapy. The presence of a subpopulation of GBM stem cells (GSC) contributes to tumour aggressiveness, resistance and recurrence. Moreover, GBM are characterised by abnormal, abundant vascularisation. Previous studies have shown that GSC are directly involved in new vessel formation via their transdifferentiation into tumour-derived endothelial cells (TDEC) and that irradiation (IR) potentiates the pro-angiogenic capacity of TDEC via the Tie2 signalling pathway. We therefore investigated the impact of regorafenib, a multikinase inhibitor with anti-angiogenic and anti-tumourigenic activity, on GSC and TDEC obtained from irradiated GSC (TDEC IR+) or non-irradiated GSC (TDEC). Regorafenib significantly decreases GSC neurosphere formation in vitro and inhibits tumour formation in the orthotopic xenograft model. Regorafenib also inhibits transdifferentiation by decreasing CD31 expression, CD31+ cell count, pseudotube formation in vitro and the formation of functional blood vessels in vivo of TDEC and TDEC IR+. All of these results confirm that regorafenib clearly impacts GSC tumour formation and transdifferentiation and may therefore be a promising therapeutic option in combination with chemo/radiotherapy for the treatment of highly aggressive brain tumours.
Physical Activity Patterns among Individuals with Prediabetes or Type 2 Diabetes across Two Years—A Longitudinal Latent Class Analysis

Background: This study aimed to identify distinct profiles of physical activity (PA) patterns among individuals with prediabetes or type 2 diabetes participating in a two-year PA trial and to investigate predictors of the profiles. Methods: Data (n = 168, collected 2013–2020) from the cohort of a randomized trial aimed at increasing PA in individuals with prediabetes and type 2 diabetes were used. PA and sedentary behaviours were assessed by waist-worn ActiGraph GT1M accelerometers at baseline and at 6, 12, 18 and 24 months. Fifteen PA and sedentary variables were entered into a latent class mixed model for multivariate longitudinal outcomes. Multinominal regression analysis modelled profile membership based on baseline activity level, age, gender, BMI, disease status and group randomisation. Results: Two profiles of PA patterns were identified: “Increased activity” (n = 37, 22%) included participants increasing time in PA and decreasing sedentary time. “No change in activity” (n = 131, 78%) included participants with no or minor changes. “Increased activity” were younger (p = 0.003) and more active at baseline (p = 0.011), compared to “No change in activity”. No other predictor was associated with profile membership. Conclusions: A majority of participants maintained PA and sedentary patterns over two years despite being part of a PA intervention. Individuals improving PA patterns were younger and more active at baseline.
Correlation of Modified Computed Tomography Severity Index with Ranson’s Criteria in Assessing Severity of Acute Pancreatitis

Introduction: Acute Pancreatitis (AP) is an illness which results in increase in morbidity and mortality when there is a delay in diagnosis and there are false results. Various scales help in making early and accurate diagnosis of AP and predict prognosis. Validity of these scales needs to be studied and compared. Balthazar score and Ranson’s criteria have been commonly used. Modified CT score’s usefulness need to be studied as it involves only CT and their early detection will help in reducing the morbidity (reducing the residual damage) and mortality. Aim: To determine validity of modified Computed Tomography Severity Index (CTSI) and Ranson’s score in assessing severity of AP and study their correlation. Materials and Methods: This is an observational study among 39 patients with AP. Ranson’s score and Modified CT index was calculated and actual outcome of the disease was observed. results: Ranson’s Score and Modified CTSI were strongly correlated with rho value of 0.912 and p-value of <0.001. Sensitivity and specificity of Ranson’s criteria in predicting the actual outcome of the disease is 80% and 83.3%, respectively. Sensitivity and specificity of Modified CT criteria in predicting the actual outcome of the disease is 93.33% and 54.17%, respectively. conclusion: From the results of this study, it is evident that Modified CT index is more sensitive than Ranson’s score, but less specific.
Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 Plays an Important Role in the Development and Reproduction of Nilaparvata lugens

Simple Summary The brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae), is a destructive insect pest of rice. It causes reductions in rice yield and great economic losses. In this study, we used RNAi to explore the function of the inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) gene in the development and reproduction of the brown planthopper. Our results revealed that ITIH4 influences the survival, ovarian development, egg production, and egg hatching of this insect, indicating that ITIH4 plays important roles in development and reproduction. Considering the importance of ITIH4 in the brown planthopper, it may be a potential target for pest management. Abstract The brown planthopper, Nilaparvata lugens, is a difficult-to-control insect pest affecting rice yields in Asia. As a structural component of the inter-alpha-trypsin inhibitor (ITI), the inter-alpha-trypsin inhibitor heavy chain (ITIH) has been reported to be involved in various inflammatory or malignant disorders, ovarian development, and ovulation. To reveal the function of ITIH4 in N. lugens, the gene encoding N. lugens ITIH4 (NlITIH4) was cloned and characterized. NlITIH4 contains a signal peptide, a vault protein inter-alpha-trypsin domain, and a von Willebrand factor type A domain. qPCR analysis showed that NlITIH4 was expressed at all developmental stages and in all tissues (fat body, ovary, and gut), with the highest expression in the fat body. Double stranded NlITIH4 (dsNlITIH4) injection clearly led to an RNAi-mediated inhibition of the expression of NlITIH4 and resulted in reduced survival, delayed ovarian development, and reduced egg production and egg hatching. These results indicate that NlITIH4 plays an important role in the development and reproduction of N. lugens.
Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance

Cancer drug resistance is the leading cause of cancer related deaths. The development of drug resistance can be partially contributed to tumor heterogeneity and epigenetic plasticity. However, the detailed molecular mechanism underlying epigenetic modulated drug resistance remains elusive. In this work, we systematically analyzed epigenetic changes in tamoxifen (Tam) responsive and resistant breast cancer cell line MCF7, and adopted a data-driven approach to identify key epigenetic features distinguishing between these two cell types. Significantly, we revealed that DNA methylation and H3K9me3 marks that constitute the heterochromatin are distinctively different between Tam-resistant and -responsive cells. We then performed time-lapse imaging of 5mC and H3K9me3 features using engineered probes. After Tam treatment, we observed a slow transition of MCF7 cells from a drug-responsive to -resistant population based on DNA methylation features. A similar trend was not observed using H3K9me3 probes. Collectively, our results suggest that DNA methylation changes partake in the establishment of Tam-resistant breast cancer cell lines. Instead of global changes in the DNA methylation level, the distribution of DNA methylation features inside the nucleus can be one of the drivers that facilitates the establishment of a drug resistant phenotype in MCF7.
Effects of Four Cropping Patterns of Lilium brownii on Rhizosphere Microbiome Structure and Replant Disease

Replant disease caused by continuous cropping obstacles commonly occurs in a Lilium brownii consecutive monoculture. To reveal the mechanisms contributing to the continuous cropping obstacles of L. brownii, four cropping patterns (fallow, L. brownii-rice rotation, newly planted L. brownii, and 2-year L. brownii consecutive monoculture) were designed, and Illumina MiSeq (16S rDNA and ITS) was utilized to detect shifts in the microbial community in the rhizosphere. Our result showed that planting of L. brownii significantly reduced soil pH. Consecutive monoculture of L. brownii can significantly decrease the diversity and abundance of soil bacteria, but markedly increase the diversity and abundance of soil fungi. Under the four planting pattern treatments, the changes in soil pH were consistent with the changes in the Shannon diversity index of soil bacterial communities, whereas we observed a negative correlation between soil pH and Shannon diversity index for fungi. The relative abundance of Lactobacillales significantly increased in soils of L. brownii consecutive monoculture, while Acidobacteriales, Solibacterales, and Xanthomonadales increased in soils of L. brownii-rice rotation and newly planted L. brownii. Collectively, this work aimed to elucidate the relationship between the L. brownii planting patterns and soil microbiome, thereby providing a theoretical basis for screening new biological agents that may contribute to resolving continuous cropping obstacles of L. brownii.
High Expression of Casein Kinase 2 Alpha Is Responsible for Enhanced Phosphorylation of DNA Mismatch Repair Protein MLH1 and Increased Tumor Mutation Rates in Colorectal Cancer

Simple Summary Colorectal cancer (CRC) is associated with DNA mismatch repair (MMR) deficiency. The serine/threonine casein kinase 2 alpha (CK2α) is able to phosphorylate and inhibit MMR protein MLH1 in vitro. This study aimed to analyze the relevance of CK2α for MLH1 phosphorylation in vivo. Around 50% of CRCs were identified to express significantly increased nuclear/cytoplasmic CK2α. High nuclear/cytoplasmic CK2α level could be significantly correlated with reduced 5-year survival outcome of patients, increased MLH1 phosphorylation, and enriched somatic tumor mutation rates. Overall, our study demonstrated, in vivo, that enhanced CK2α leads to an increase of MLH1 phosphorylation, higher tumor mutation rates, and is an unfavorable prognosis for patients. Abstract DNA mismatch repair (MMR) deficiency plays an essential role in the development of colorectal cancer (CRC). We recently demonstrated in vitro that the serine/threonine casein kinase 2 alpha (CK2α) causes phosphorylation of the MMR protein MLH1 at position serine 477, which significantly inhibits the MMR. In the present study, CK2α-dependent MLH1 phosphorylation was analyzed in vivo. Using a cohort of 165 patients, we identified 88 CRCs showing significantly increased nuclear/cytoplasmic CK2α expression, 28 tumors with high nuclear CK2α expression and 49 cases showing a general low CK2α expression. Patients with high nuclear/cytoplasmic CK2α expression demonstrated significantly reduced 5-year survival outcome. By immunoprecipitation and Western blot analysis, we showed that high nuclear/cytoplasmic CK2α expression significantly correlates with increased MLH1 phosphorylation and enriched somatic tumor mutation rates. The CK2α mRNA levels tended to be enhanced in high nuclear/cytoplasmic and high nuclear CK2α-expressing tumors. Furthermore, we identified various SNPs in the promotor region of CK2α, which might cause differential CK2α expression. In summary, we demonstrated that high nuclear/cytoplasmic CK2α expression in CRCs correlates with enhanced MLH1 phosphorylation in vivo and seems to be causative for increased mutation rates, presumably induced by reduced MMR. These observations could provide important new therapeutic targets.
Diagnostic and Prognostic Roles of CDX2 Immunohistochemical Expression in Colorectal Cancers

The study is aimed to evaluate the diagnostic and prognostic role of the immunohistochemical expression of the Caudal-type homeobox transcription factor 2 (CDX2) in colorectal cancers (CRCs) through a meta-analysis. By searching relevant databases, 38 articles were eligible to be included in this study. We extracted the information for CDX2 expression rates and the correlation between CDX2 expression and clinicopathological characteristics. The estimated rates of CDX2 expression were 0.882 [95% confidence interval (CI) 0.774–0.861] and 0.893 (95% CI 0.820–0.938) in primary and metastatic CRCs, respectively. Furthermore, based on their histologic subtype, CDX2 expression rates of adenocarcinoma and medullary carcinoma were 0.886 (95% CI 0.837–0.923) and 0.436 (95% CI 0.269–0.618), respectively. There was a significant difference in CDX2 expression rates between adenocarcinoma and medullary carcinoma in the meta-regression test (p < 0.001). In addition, CDX2 expression was significantly lower in CRCs with the BRAFV600E mutation than in CRCs without mutation. Patients with CDX2 expression had better overall and cancer-specific survival rates than those without CDX2 expression. Thus, CDX2 is a useful diagnostic and prognostic marker CRCs.
Polyomavirus Localized with Deep Learning Methods

This case study shows how to apply a deep learning algorithm to detect specific particles in transmission electron microscopy images. The main difficulty consists in the confusing background where a mix of artifacts introduced by the negative staining method coexist with biological debris, and low contrast inherent to the acquisition process of the samples. Considering that a high-resolution 3D reconstruction of virus particles or other macromolecular structures needs thousands of particles, the recent advances in deep-learning methods makes the reach of a comfortable number of particles attainable with a high level of confidence. Deep learning algorithms based on convolutional neural networks can overcome the major issues after a train and validation stage, and subsequently process thousands of similar images in a short amount of time, with a few seconds required for each image, localizing all the particles of interest with very few mistakes, or missed particles. We applied one of such algorithms to a dataset of polyomavirus images containing about 390 particles and evaluate its performance against human curation, verifying that 88.9% of the dataset were processed with zero false positive detections.
Research on Driving Performances of Electric Transmission Tracked Vehicles Based on Torque Control Strategy

The feasibility study on controlling the movement of an electric transmission tracked vehicle through controlling the output torques of left and right side motors directly was discussed in principle.The torque control strategy was put forward.The 3-D multi-body dynamics virtual prototype model of tracked vehicle running gear and the models of integrated controller and motor control systems were built based on multi-body dynamics analysis software RecurDyn/TrackHM and control system analysis software Matlab/Simulink.Also,the collaborative simulation model based on interface technology of different softwares was built.Under the conditions of the acceleration time(0～32 km/h),straight-line offset data in 100 m at different velocities,B/2 steering and climb ability of 15° slope,the vehicle's driving performances were researched by collaborative simulation and reality vehicle test.The correctness of the model and torque control strategy is validated by analysis and comparison,which lays the foundation for further research on other driving performances.
Constructing Condition Monitoring Model of Wind Turbine Blades

Wind power has become an indispensable part of renewable energy development in various countries. Due to the high cost and complex structure of wind turbines, it is important to design a method that can quickly and effectively determine the structural health of the generator set. This research proposes a method that could determine structural damage or weaknesses in the blades at an early stage via a model to monitor the sound of the wind turbine blades, so as to reduce the quantity of labor required and frequency of regular maintenance, and to repair the damage rapidly in the future. This study used the operating sounds of normal and abnormal blades as a dataset. The model used discrete wavelet transform (DWT) to decompose the sound into different frequency components, performed feature extraction in a statistical measure, and combined with outlier exposure technique to train a deep neural network model that could capture abnormal values deviating from the normal samples. In addition, this paper observed that the performance of the monitoring model on the MIMII dataset was also better than the anomaly detection models proposed by other papers.
An investigation on using teaching media in teaching speaking skill

Teaching media is a mode and learning messages to students that can help teachers to improve students’ learning achievement. This study aimed at finding kinds of the teaching media used by teacher in teaching speaking skill and the obstacles that she encountered in using teaching media. This study is a qualitative study. There were one teacher and one online class meeting involved in this study. To collect the data, the researcher employed observation via Zoom Cloud Meeting recording and interview. The result of the study indicates that there are 8 of teaching media which are generally used by the teacher, comprising: Zoom application, WhatsApp group, Microsoft word and Microsoft PowerPoint, video, YouTube, whiteboard, and course book. The teacher faced the obstacles toward the difference background of students’ ability, the number of the students, the availability of network, and the teacher’s less attention in using teaching media. In short, the teacher should consider the appropriateness of teaching materials to the students’ level of intelligence because it will help them to understand the material successfully.
Dispersion Engineering of Silicon Nitride Microresonators via Reconstructable SU-8 Polymer Cladding

In this work, we propose a novel way to flexibly engineer the waveguide dispersion by patterning the cladding of waveguide microresonators. Experimentally, we demonstrate silicon nitride waveguides with air-, oxide-, and SU-8 polymer-cladding layers and compare the corresponding waveguide dispersion. By integrating SU-8 polymer as the outer cladding layer, the waveguide dispersion can be tuned from −143 to −257 ps/nm/km. Through the simple, conventional polymer stripping process, we reconstruct the waveguide dispersion back to that of the original air-cladded device without significantly impacting the quality factor of resonators. This work provides the potential to design the waveguide dispersion in normal and anomalous regimes within an integrated photonic circuit.
OMT-based FMS Modeling

Modeling study is very important for the automatic generation of dynamic software for FMS. Object Mode Technology (OMT) originates from simulation and adopts the object oriented modeling method, and has great advantages in the analysis, modeling and automatic generation of dynamics schedule software for FMS. In this paper, the OMT based modeling method is investigated firstly. Then, the object mode, function mode and dynamic mode are built, which lays a solid foundations for the automatic generation of dynamic simulation software for FMS .