MLRR-ATV: A Robust Manifold Nonnegative LowRank Representation with Adaptive Total-Variation Regularization for scRNA-seq Data Clustering.

Since genomics was proposed, the exploration of genes has been the focus of research. The emergence of single-cell RNA sequencing (scRNA-seq) technology makes it possible to explore gene expression at the single-cell level. Due to the limitations of sequencing technology, the data contains a lot of noise. At the same time, it also has the characteristics of highdimensional and sparse. Clustering is a common method of analyzing scRNA-seq data. This paper proposes a novel singlecell clustering method called Robust Manifold Nonnegative LowRank Representation with Adaptive Total-Variation Regularization (MLRR-ATV). The Adaptive Total-Variation (ATV) regularization is introduced into Low-Rank Representation (LRR) model to reduce the influence of noise through gradient learning. Then, the linear and nonlinear manifold structures in the data are learned through Euclidean distance and cosine similarity, and more valuable information is retained. Because the model is non-convex, we use the Alternating Direction Method of Multipliers (ADMM) to optimize the model. We tested the performance of the MLRRATV model on eight real scRNA-seq datasets and selected nine state-of-the-art methods as comparison methods. The experimental results show that the performance of the MLRRATV model is better than the other nine methods.

Cauchy hyper-graph Laplacian nonnegative matrix factorization for single-cell RNA-sequencing data analysis.

Many important biological facts have been found as single-cell RNA sequencing (scRNA-seq) technology has advanced. With the use of this technology, it is now possible to investigate the connections among individual cells, genes, and illnesses. For the analysis of single-cell data, clustering is frequently used. Nevertheless, biological data usually contain a large amount of noise data, and traditional clustering methods are sensitive to noise. However, acquiring higher-order spatial information from the data alone is insufficient. As a result, getting trustworthy clustering findings is challenging. We propose the Cauchy hyper-graph Laplacian non-negative matrix factorization (CHLNMF) as a unique approach to address these issues. In CHLNMF, we replace the measurement based on Euclidean distance in the conventional non-negative matrix factorization (NMF), which can lessen the influence of noise, with the Cauchy loss function (CLF). The model also incorporates the hyper-graph constraint, which takes into account the high-order link among the samples. The CHLNMF model's best solution is then discovered using a half-quadratic optimization approach. Finally, using seven scRNA-seq datasets, we contrast the CHLNMF technique with the other nine top methods. The validity of our technique was established by analysis of the experimental outcomes.

Case Report: Persistent response to combination therapy of pemigatinib, chemotherapy, and immune checkpoint inhibitor in a patient with advanced intrahepatic cholangiocarcinoma.

Patients with advanced intrahepatic cholangiocarcinoma (iCCA) often have a poor prognosis. Recent advancements in targeted molecular therapy and immunotherapy have been made. Herein, we report a case of advanced iCCA treated with a combination of pemigatinib (a selective FGFR inhibitor), chemotherapy, and an immune checkpoint inhibitor. A 34-year-old female was diagnosed with advanced iCCA with multiple liver masses and metastases in the peritoneum and lymph nodes. Next-generation sequencing (NGS) identified the genetic mutations. An FGFR2-BICC1 gene fusion was found in this patient. The patient was treated with pemigatinib in combination with pembrolizumab plus systemic gemcitabine and oxaliplatin. After 9 cycles of the combination therapy, the patient achieved a partial response, complete metabolic response, and normalization of tumor markers. Sequentially, the patient received pemigatinib and pembrolizumab for 3 months. Due to the elevated tumor biomarker, she is currently receiving chemotherapy, pemigatinib, and pembrolizumab treatment again. She regained an excellent physical status after 16 months of treatment. To the best of our knowledge, this was the first reported case of advanced iCCA successfully treated with a combination of pemigatinib, chemotherapy, and ICIs as a first-line regimen. This treatment combination may be effective and safe in the advanced iCCA.

Significance of interstitial fibrosis and p16 in papillary thyroid carcinoma.

We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor-node-metastasis (pTNM) stage and age (p < 0.05). The cancer-specific survival (CSS) was longer in p16-negative patients (195.73 vs. 181.78 months, p = 0.007). p16 was significantly related to the degree of IF (r = 0.130, p = 0.035). PTC patients with no or mild fibrosis tended to have a larger tumor (p = 0.045). The degree of fibrosis was related to the proportion of papillary structure components (p = 0.025). Univariate and multivariate survival analyses showed that relapse-free survival (RFS) was longer in patients with moderate/severe IF (p < 0.05). In summary, p16 was correlated with prognosis and IF of PTC. Patients with moderate/severe IF tend to have better prognosis in RFS.

Influence of the Cross-Sectional Shape and Corner Radius on the Compressive Behaviour of Concrete Columns Confined by FRP and Stirrups.

Axial compression tests were carried out on 72 FRP (fiber reinforced polymer)-stirrup composite-confined concrete columns. Stirrups ensure the residual bearing capacity and ductility after the FRP fractures. To reduce the effect of stress concentration at the corners of the confined square-section concrete columns and improve the restraint effect, an FRP-stirrup composite-confined concrete structure with rounded corners is proposed. Different corner radii of the stirrup and outer FRP were designed, and the corner radius of the stirrup was adjusted accurately to meet the designed corner radius of the outer FRP. The cross-section of the specimens gradually changed from square to circular as the corner radius increased. The influence of the cross-sectional shape and corner radius on the compressive behaviour of FRP-stirrup composite-confined concrete was analysed. An increase in the corner radius can cause the strain distribution of the FRP to be more uniform and strengthen the restraint effect. The larger the corner radius of the specimen, the better the improvement of mechanical properties. The strength of the circular section specimen was greatly improved. In addition, the test parameters also included the FRP layers, FRP types and stirrup spacing. With the same corner radius, increasing the number of FRP layers or densifying the stirrup spacing effectively improved the mechanical properties of the specimens. Finally, a database of FRP-stirrup composite-confined concrete column test results with different corner radii was established. The general calculation models were proposed, respectively, for the peak points, ultimate points and stress-strain models that are applicable to FRP-, stirrup- and FRP-stirrup-confined concrete columns with different cross-sectional shapes under axial compression.

Compressive Behavior of Bamboo Sheet Twining Tube-Confined Concrete Columns.

This study experimentally investigated various axial compressive parameters of a new type of confined concrete, which is termed bamboo sheet twining tube-confined concrete (BSTCC). This new composite structure was composed of an outer bamboo composite tube (BCT) jacket and a concrete core. Under axial compression, the parameters of thirty-six specimens include concrete strength (i.e., C30 and C50) and BCT thickness (i.e., 6, 12, 18, 24, and 30 layers). The mechanical properties of the BSTCC specimens from the perspective of the failure mode, stress-strain relationship, effect of BCT thickness and dilation behavior were analyzed. The results showed that, in compression, with an increase in BCT thickness in the range of 18-layers of bamboo sheets, the strength increased remarkably. When the strength of the concrete core was high, the confinement effect of the BCT was reduced. In addition, the BCT thickness relieved the dilation of the BSTCC specimens. Finally, the experimental results were compared with predictions obtained from 7 existing FRP-confined concrete models. All the predictions had good agreement with the test results, which further confirmed that the models developed for FRP-confined concrete can provide an acceptable approximation of the ultimate strength of the BSTCC specimens.

Relationship between mismatch repair protein, RAS, BRAF, PIK3CA gene expression and clinicopathological characteristics in elderly colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is common in elderly patients. Mismatch repair (MMR) protein deletion is one of the causes of CRC. The RAS (KRAS/NRAS), BRAF, and PIK3CA genes are important gene targets in CRC treatment and are closely related to the prognosis and survival of patients. However, little is known regarding the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC patients. AIM: To analyze the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC. METHODS: A total of 327 elderly patients with CRC were enrolled, and immuno-histochemistry was used to detect the MMR protein. Real-time quantitative polymerase chain reaction was used to detect the RAS (KRAS/NRAS), BRAF, and PIK3CA genes. The clinicopathological data of the patients were recorded and analyzed by SPSS 19.0 statistical software. RESULTS: In 327 elderly patients with CRC, the rate of MMR protein loss was 9.79% (32/327), and the deletion rate of four MMR proteins (MSH2, MSH6, MLH1, PMS2) was 1.83% (6/327), 3.06% (10/327), 7.65% (25/327), and 7.65% (25/327), respectively. There were no significant differences between MMR protein deletion and sex, pathological type, tumor morphology, differentiation degree or lymph node metastasis (P > 0.05), but there was a significant difference between MMR protein deletion and tumor diameter and tumor location (P = 0.048/P = 0.000). The mutation rates of the KRAS, NRAS, BRAF and PIK3CA genes in elderly CRC patients were 44.95% (147/327), 2.45% (8/327), 3.36% (11/327) and 2.75% (9/327), respectively; the KRAS gene mutation was closely related to tumor morphology (P = 0.002) but not to other clinicopathological features (P > 0.05), and there were no significant differences between NRAS gene mutation and clinicopathological features (P > 0.05). The BRAF gene mutation showed a significant difference in pathological type, tumor location, differentiation degree and lymph node metastasis (P < 0.05), but was not correlated with sex, tumor size and tumor morphology (P > 0.05). The PIK3CA gene mutation showed no significant differences in the above clinicopathological characteristics (P > 0.05). Significant differences were observed between MMR protein deletion and KRAS, BRAF, and PIK3CA gene mutations in elderly CRC patients (P = 0.044, P = 0.000, P = 0.003, respectively), but there was no significant difference between MMR protein deletion and NRAS mutation (P > 0.05). CONCLUSION: In elderly CRC patients, the tumor is mainly located in the right colon, and the deletion rate of MMR protein is higher when the tumor diameter is greater than or equal to 5 cm; the deletion rate of MLH1 and PMS2 is more common; the mutation rate of KRAS gene is higher than that of the NRAS, BRAF and PIK3CA genes, the BRAF gene mutation has different degrees of correlation with clinicopathological characteristics; when the MMR protein is deleted, the BRAF and PIK3CA gene mutations are often present, and the KRAS gene mutation rate is low.

Deep sequencing of the Sanghuangporus vaninii transcriptome reveals dynamic landscapes of candidate genes involved in the biosynthesis of active compounds.

The medicinal fungus Sanghuang produces diverse bioactive compounds and is widely used in Asian countries. However, little is known about the genes and pathways involved in the biosynthesis of these active compounds. Based on our previous study providing Sanghuangporus vaninii genomic information, the transcriptomes of MY (mycelium), OY (1-year-old fruiting bodies), and TY (3-year-old fruiting bodies) were determined in this study. A significant number of genes (4774) were up- or downregulated between mycelium and fruiting bodies, but only 1422 differentially expressed genes were detected between OY and TY. 138 genes encoding P450s were identified in the fungal genome and grouped into 25 P450 families; more than 64% (88) of the genes were significantly differentially expressed between the mycelium and fruiting body, suggesting that these P450s are involved in fungal sexual development. Importantly, the expression of genes involved in bioactive compound (triterpenoids, polysaccharides, and flavonoids) biosynthesis in asexual (cultured with solid and liquid media) and sexual stages was explored and combined with transcriptome and quantitative PCR analyses. More genes involved in the biosynthesis of bioactive compounds were expressed more highly in mycelium than in fruiting bodies under liquid medium culture compared with solid medium culture, which was consistent with the yields of different bioactive compounds, suggesting that liquid fermentation of S. vaninii Kangneng can be used to obtain these bioactive compounds. A comprehensive understanding of the genomic information of S. vaninii will facilitate its potential use in pharmacological and industrial applications.

Clinical study on a skin stretching technique with adjustable external fixators to treat skin defects.

The aim of this study was to determine the effectiveness of a skin stretching technique with adjustable external fixators in treating skin defects.Eighteen patients treated with a skin-stretching technique with adjustable external fixators for skin defects from April 2017 to October 2019 were included. Visual Analogue Scale (VAS) scores were collected during therapy. The skin defects gradually became smaller until they were completely resolved according to the blood flow of the affected limb and wound skin (the color, temperature, elasticity, and capillary response). The defect sizes ranged from 4 cm × 2 cm to 20 cm × 6 cm.The 18 adjustable external fixators were dismantled in 2 to 9 days (mean, 4.05 days) after the operation, and the defects were completely closed and the sutures were removed after 2 to 3 weeks. The average VAS score was 5.97. The follow-up period was 4 to 12 months (mean, 6.3 months); 17 patients healed well with linear small scar, and no infections or patients of necrosis were observed. Sensory recovery was assessed using the Medical Research Council scale, and all the sensation scores were S3+. Eight patients were healed after the first stage. Nine patients were closed totally while small sinus or skin defect were observed after sutures were removed; 3 patients were healed after the second debridement, and 6 patients finally healed after the dressings were changed. Patellar osteomyelitis recurred in 1 patient who was transferred to the Orthopedic Department for further treatment, and a flap graft procedure was performed.The operation was simple and obviously reduced the course of the disease, the costs, and the damage to the donor site, and it is also significantly superior to skin graft or flap transplantation procedures in terms of the resulting skin sensation, color, texture, elasticity, and appearance.