A multicenter study: predicting KRAS mutation and prognosis in colorectal cancer through a CT-based radiomics nomogram.

PURPOSE: To establish a CT-based radiomics nomogram for preoperative prediction of KRAS mutation and prognostic stratification in colorectal cancer (CRC) patients. METHODS: In a retrospective analysis, 408 patients with confirmed CRC were included, comprising 168 cases in the training set, 111 cases in the internal validation set, and 129 cases in the external validation set. Radiomics features extracted from the primary tumors were meticulously screened to identify those closely associated with KRAS mutation. Subsequently, a radiomics nomogram was constructed by integrating these radiomics features with clinically significant parameters. The diagnostic performance was assessed through the area under the receiver operating characteristic curve (AUC). Lastly, the prognostic significance of the nomogram was explored, and Kaplan-Meier analysis was employed to depict survival curves for the high-risk and low-risk groups. RESULTS: A radiomics model was constructed using 19 radiomics features significantly associated with KRAS mutation. Furthermore, a nomogram was developed by integrating these radiomics features with two clinically significant parameters (age, tumor location). The nomogram achieved AUCs of 0.834, 0.813, and 0.811 in the training set, internal validation set, and external validation set, respectively. Additionally, the nomogram effectively stratified patients into high-risk (KRAS mutation) and low-risk (KRAS wild-type) groups, demonstrating a significant difference in overall survival (P < 0.001). Patients categorized in the high-risk group exhibited inferior overall survival in contrast to those classified in the low-risk group. CONCLUSIONS: The CT-based radiomics nomogram demonstrates the capability to effectively predict KRAS mutation in CRC patients and stratify their prognosis preoperatively.

The Role of Indoor Microbiome and Metabolites in Shaping Children's Nasal and Oral Microbiota: A Pilot Multi-Omic Analysis.

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

Chiral Skeletons of Mesoporous Silica Nanospheres to Mitigate Alzheimer's ß-Amyloid Aggregation.

Chiral mesoporous silica (mSiO2) nanomaterials have gained significant attention during the past two decades. Most of them show a topologically characteristic helix; however, little attention has been paid to the molecular-scale chirality of mSiO2 frameworks. Herein, we report a chiral amide-gel-directed synthesis strategy for the fabrication of chiral mSiO2 nanospheres with molecular-scale-like chirality in the silicate skeletons. The functionalization of micelles with the chiral amide gels via electrostatic interactions realizes the growth of molecular configuration chiral silica sols. Subsequent modular self-assembly results in the formation of dendritic large mesoporous silica nanospheres with molecular chirality of the silica frameworks. As a result, the resultant chiral mSiO2 nanospheres show abundant large mesopores (∼10.1 nm), high pore volumes (∼1.8 cm3·g-1), high surface areas (∼525 m2·g-1), and evident CD activity. The successful transfer of the chirality from the chiral amide gels to composited micelles and further to asymmetric silica polymeric frameworks based on modular self-assembly leads to the presence of molecular chirality in the final products. The chiral mSiO2 frameworks display a good chiral stability after a high-temperature calcination (even up to 1000 °C). The chiral mSiO2 can impart a notable decline in ß-amyloid protein (Aß42) aggregation formation up to 79%, leading to significant mitigation of Aß42-induced cytotoxicity on the human neuroblastoma line SH-ST5Y cells in vitro. This finding opens a new avenue to construct the molecular chirality configuration in nanomaterials for optical and biomedical applications.

A novel inflammasome-related gene nomogram predicts survival in hepatocellular carcinoma.

Inflammasomes are closely associated with the progression of multiple cancers. We established an inflammasome-related gene (IRG)-based model to predict the survival of patients with hepatocellular carcinoma (HCC). The RNA-sequencing data and clinical information of HCC patients were downloaded from the cancer genome atlas-liver hepatocellular carcinoma database, and the differentially expressed inflammasome-related gene were screened. Seven prognostic differentially expressed inflammasome-related genes were identified by univariate Cox analysis and incorporated into the risk model using least absolute shrinkage and selection operator-Cox algorithm. The predictive accuracy of the risk model was evaluated through the Kaplan-Meier, receiver operating characteristic and Cox regression analyses. The performance of the model was verified in the International Cancer Genome Consortium-Liver Cancer - RIKEN, JP cohort. A nomogram was constructed to predict the 1-, 2-, 3- ,and 5-year survival of HCC patients, and its performance was evaluated using calibration curves. The significantly enriched gene ontology terms, Kyoto encyclopedia of genes and genomes pathways and infiltrating immune cell populations associated with the IRG model were also analyzed to explore of the potential molecular mechanisms and immunotherapeutic targets. An independent and highly accurate prognostic model consisting of 7 IRGs was established and verified in 2 independent HCC cohorts. The IRG model was significantly associated with cell division and cell cycle. In addition, the high-risk group was more likely to have greater infiltration of immune cells and higher expression of immune checkpoint-related genes compared to the low-risk group. An IRG-based model was established to predict 1-, 2-, 3-, and 5-year survival rate in individual HCC patients, which provides new insights into the role of inflammasomes in HCC.

([2.2.2]Cryptand)potassium (4-methyl-benzene-thiol-ato)[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyr-inato]manganate(II) tetra-hydro-furan disolvate.

Single crystals of the title compound, [K(C18H36N2O6)][Mn(C44H24Cl4N4)(C7H7S)]·2C4H8O, were obtained by the solvent evaporation method. The MnII cation is coordinated by four pyrrole N atoms (Np) of the porphyrin ring and one S atom of the apical 4-methyl-benzene-thiol-ate ligand with the average Mn-Np and the apical Mn-S bond lengths being 2.160 (9) and 2.4642 (8) Å, respectively. Two tetra-hydro-furan solvent mol-ecules and a potassium cation chelated inside a [2.2.2]cryptand (4,7,13,16,21,24-hexa-oxa-1,10-di-aza-bicyclo[8.8.8]hexa-cosa-ne) are also present.

Aberrant gene expression pattern in the glycolysis-cholesterol synthesis axis is linked with immune infiltration and prognosis in prostate cancer: A bioinformatics analysis.

Aberrant lipid metabolism is an early event in tumorigenesis and has been found in a variety of tumor types, especially prostate cancer (PCa). Therefore, We hypothesize that PCa can be stratified into metabolic subgroups based on glycolytic and cholesterogenic related genes, and the different subgroups are closely related to the immune microenvironment. Bioinformatics analysis of genomic, transcriptomic, and clinical data from a comprehensive cohort of PCa patients was performed. Datasets included the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) dataset, GSE70768, our previously published PCa cohort. The unsupervised cluster analysis was employed to stratify PCa samples based on the expression of metabolic-related genes. Four molecular subtypes were identified, named Glycolytic, Cholesterogenic, Mixed, and Quiescent. Each metabolic subtype has specific features. Among the 4 subtypes, the cholesterogenic subtype exhibited better median survival, whereas patients with high expression of glycolytic genes showed the shortest survival. The mitochondrial pyruvate carriers (MPC) 1 exhibited expression difference between PCa metabolic subgroups, but not for MPCs 2. Glycolytic subtypes had lower immune cell scores, while Cholesterogenic subgroups had higher immune cell scores. Our results demonstrated that metabolic classifications based on specific glycolytic and cholesterol-producing pathways provide new biological insights into previously established subtypes and may guide develop personalized therapies for unique tumor metabolism characteristics.

Identification of immune-based prostate cancer subtypes using mRNA expression.

Immune infiltration in Prostate Cancer (PCa) was reported to be strongly associated with clinical outcomes. However, previous research could not elucidate the diversity of different immune cell types that contribute to the functioning of the immune response system. In the present study, the CIBERSORT method was employed to evaluate the relative proportions of immune cell profiling in PCa samples, adjacent tumor samples and normal samples. Three types of molecular classification were identified in tumor samples using the 'CancerSubtypes' package of the R software. Each subtype had specific molecular and clinical characteristics. In addition, functional enrichment was analyzed in each subtype. The submap and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were also used to predict clinical response to the immune checkpoint blockade. Moreover, the Genomics of Drug Sensitivity in Cancer (GDSC) database was employed to screen for potential chemotherapeutic targets for the treatment of PCa. The results showed that Cluster I was associated with advanced PCa and was more likely to respond to immunotherapy. The findings demonstrated that differences in immune responses may be important drivers of PCa progression and response to treatment. Therefore, this comprehensive assessment of the 22 immune cell types in the PCa Tumor Environment (TEM) provides insights on the mechanisms of tumor response to immunotherapy and may help clinicians explore the development of new drugs.

Correction of Scoliosis with Large Thoracic Curves in Marfan Syndrome: Does the High-Density Pedicle Screw Construct Contribute to Better Surgical Outcomes.

BACKGROUND The aim of this study was to determine whether higher density screw constructs resulted in better surgical outcomes in patients with scoliosis secondary to Marfan syndrome (MF-S) with large thoracic curves (≥70°). MATERIAL AND METHODS There were 34 MF-S patients who met the inclusion criteria and were evaluated radiographically before surgery, 2 weeks after operation, and at the final follow-up. The mean screw density was taken as the boundary, and patients were categorized as either in the high density (HD) group or the low density (LD) group. Parameters measured included coronal Cobb angle, T5-T12 kyphosis (TK), and T12-S1 lordosis (LL). Additionally, the operation duration, estimated blood loss, screw accuracy, complication rate, and clinical outcomes were compared between the 2 groups. RESULTS The mean screw density of all patients was 1.40±0.15 (range 1.13 to 1.67). Correction rate of the thoracic curve was closely related to the screw density at the concave side (r=0.783, P=0.007). Intergroup comparison showed a significantly higher correction rate of the thoracic coronal curve in HD group (56.59±4.80% versus 44.54±9.61%, P=0.036). At last follow-up, coronal correction loss of >5° occurred in 8 cases (47.1%) in the LD group and 3 cases (17.6%) in the HD group. Both groups demonstrated improvement in each domain of the SRS-22 questionnaire after surgery and no significant intergroup difference was found. CONCLUSIONS The high-density pedicle screw construct contributed to the significantly improved correction rate of thoracic curves in MF-S patients with large thoracic curves (≥70°). Additionally, increasing of pedicle screw number could help to enhance the structural stability and reduce the correction loss during the follow-up period.

Systematic analysis of differentially methylated expressed genes and site-specific methylation as potential prognostic markers in head and neck cancer.

Head and neck cancer (HNC) remains one of the most malignant tumors with a significantly high mortality. DNA methylation exerts a vital role in the prognosis of HNC. In this study, we try to screen abnormal differential methylation genes (DMGs) and pathways in Head-Neck Squamous Cell Carcinoma via integral bioinformatics analysis. Data of gene expression microarrays and gene methylation microarrays were obtained from the Cancer Genome Atlas database. Aberrant DMGs were identified by the R Limma package. We conducted the Cox regression analysis to select the prognostic aberrant DMGs and site-specific methylation. Five aberrant DMGs were recognized that significantly correlated with overall survival. The prognostic model was constructed based on five DMGs (PAX9, STK33, GPR150, INSM1, and EPHX3). The five DMG models acted as prognostic biomarkers for HNC. The area under the curve based on the five DMGs predicting 5-year survival is 0.665. Moreover, the correlation between the DMGs/site-specific methylation and gene expression was also explored. The findings demonstrated that the five DMGs can be used as independent prognostic biomarkers for predicting the prognosis of patients with HNC. Our study might lay the groundwork for further mechanism exploration in HNC and may help identify diagnostic biomarkers for early stage HNC.

Radiographic and Clinical Outcomes of Surgical Correction of Poliomyelitis-Related Spinal Deformities: A Comparison Among Three Types of Pelvic Instrumentations.

BACKGROUND: We compared the clinical and radiographic outcomes of corrective surgery in patients with poliomyelitis-related spinal deformity (PSD) using 3 types of pelvic fixation and investigated the incidence and risk factors for complications. METHODS: We reviewed the data from 42 patients with PSD who had undergone spinopelvic reconstruction at a single institution from 2000 to 2016. Of the 42 patients, 15 had been treated with the Galveston technique, 13 with iliac screw fixation, and 14 with S2-alar-iliac (S2AI) screw fixation. Demographic data, radiographic parameters, and complications were analyzed. Health-related quality of life was determined using Scoliosis Research Society (SRS) 22-item questionnaires and the Oswestry Disability Index scores. RESULTS: After surgery, the correction rate of the main curve was 51.7%, 57.8%, and 52.1% in the 3 groups, with significant improvement in regional kyphosis, coronal balance, and pelvic obliquity (PO) (P < 0.05). The correction of PO was similar among the 3 types of pelvic fixation; however, the patients treated with S2AI fixation required significantly less operative time (P < 0.05) and blood loss (P < 0.006). The overall complication rate was 40.5%, with a major complication rate of 23.8%. Age at surgery (P = 0.006) and grade >2 SRS-Schwab osteotomy (P = 0.036) were significant risk factors for complications. Significant improvement was found in the SRS-22 and Oswestry Disability Index scores at the final follow-up examination in the 3 groups. CONCLUSIONS: The present study showed satisfactory correction of spinopelvic deformity for 42 patients with PSD. Compared with the Galveston technique and iliac screw fixation, the use of S2AI significantly decrease the operative time and estimated blood loss and obtained similar correction of PO. Patient age at surgery and grade >2 SRS-Schwab osteotomy were significant risk factors for complications.