Development and Validation of an Efficient MRI Radiomics Signature for Improving the Predictive Performance of 1p/19q Co-Deletion in Lower-Grade Gliomas

The prognosis and treatment plans for patients diagnosed with low-grade gliomas (LGGs) may significantly be improved if there is evidence of chromosome 1p/19q co-deletion mutation. Many studies proved that the codeletion status of 1p/19q enhances the sensitivity of the tumor to different types of therapeutics. However, the current clinical gold standard of detecting this chromosomal mutation remains invasive and poses implicit risks to patients. Radiomics features derived from medical images have been used as a new approach for non-invasive diagnosis and clinical decisions. This study proposed an eXtreme Gradient Boosting (XGBoost)-based model to predict the 1p/19q codeletion status in a binary classification task. We trained our model on the public database extracted from The Cancer Imaging Archive (TCIA), including 159 LGG patients with 1p/19q co-deletion mutation status. The XGBoost was the baseline algorithm, and we combined the SHapley Additive exPlanations (SHAP) analysis to select the seven most optimal radiomics features to build the final predictive model. Our final model achieved an accuracy of 87% and 82.8% on the training set and external test set, respectively. With seven wavelet radiomics features, our XGBoost-based model can identify the 1p/19q codeletion status in LGG-diagnosed patients for better management and address the drawbacks of invasive gold-standard tests in clinical practice.

Macular corneal dystrophy related to novel mutations of CHST6 in a Chinese family and clinical observation after penetrating keratoplasty

Background Macular corneal dystrophy (MCD) is a rare corneal stromal dystrophy with bilateral progressive vision loss. The pathogenic gene of MCD is carbohydrate sulfotransferase 6 (CHST6). Herein, we report a novel missense mutation and a rare exon deletion mutation in the CHST6 gene in a Chinese family with MCD. Methods Genomic DNA was extracted from the peripheral blood, and next generation sequencing was used to analyse the gene sequence. The pathogenic mutations were identified in all affected family members. The proband successively received binocular penetrating keratoplasty (PKP), and the corneas were examined by histopathology and colloidal iron staining to prove the diagnosis. A long-term follow-up was made to observe the changes after PKP. Results Genetic analysis demonstrated hemizygous mutations in the proband, including a novel c.520A>C (p.K174Q) missense mutation and a rarely reported exon 3 deletion mutation, which were co-segregated with the MCD phenotypes in the pedigree. The positive colloidal iron staining confirmed the diagnosis of MCD in the proband. However, the clinical phenotype and pathological manifestation of both eyes were different from each other because of complicated keratitis in the left eye. During the nine years of follow-up, visual acuity was improved significantly, and the cornea was transparent without rejection and postoperative recurrence in both eyes. Conclusions The novel hemizygous mutations were thought to contribute to the loss of CHST6 function, which induced typical clinical and pathological features of MCD. PKP was an effective treatment for MCD.

Use of transcriptional slippage for diverse gene expression

We present here an alternative for two-promoter systems ensuring highly diverse expression of several genes from a single promoter. This approach assumes an introduction of a deletion mutation into an A/T homopolymeric run in a gene’s proximal part, and employs the transcriptional slippage mechanism for insertion-dependent reinstatement of the proper reading frame by the T7 RNA polymerase.

SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance

SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.

Chinese Medicine Combined With EGFR-TKIs Prolongs Progression-Free Survival and Overall Survival of Non-small Cell Lung Cancer (NSCLC) Patients Harboring EGFR Mutations, Compared With the Use of TKIs Alone

Objective: To explore the efficacy comparison between epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) combined with traditional Chinese medicine (TCM) and single EGFR-TKIs for advanced non-small cell lung cancer (NSCLC).Methods: A total of 91 NSCLC patients with EGFR mutation were divided into an experimental group and a control group (in a ratio of 2:1) to receive TCM and EGFR-TKIs (61 cases) or single EGFR-TKIs (30 cases). Patients in the control group took EGFR-TKIs and those in the experimental group took EGFR-TKIs plus TCM. We analyzed the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events of two groups.Results: The mPFS of the experimental group and the control group was 12.3 and 8.9 months (P = 0.02), respectively, and the mOS of the experimental group and the control group was 28.2 and 24.2 months (P = 0.02), respectively. Subgroup analysis showed that for the patients with exon 19 deletion mutation (19DEL), mPFS between experimental group and control group was 12.7 and 10.1 months, respectively (P = 0.12). For exon 21 deletion mutation (L858R), the PFS of two groups was 10.8 vs. 8.2 months, respectively (P = 0.03). The subgroup analysis also showed that, for the patients with exon 19 deletion mutation, mOS between the experimental group and the control group was 30.3 and 28.7 months, respectively (P = 0.19). For exon 21 deletion mutation, the mOS of two groups was 25.5 vs. 21.3 months, respectively (P = 0.01). The DCR of the experimental group and the control group was 93.3% and 80.1%, respectively (P = 0.77). Grade 3–4 treatment-related adverse events were less common with the experimental group (11.48%) than the control group (26.67%).Conclusion: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM had a certain effect to prolong mPFS and mOS, compared with the use of EGFR-TKIs alone, especially for the patients with L858R. This conclusion has a significant effect on improving the survival of NSCLC patients after EGFR-TKIs resistance. It deserves further study.