Deep learning model based on multi-lesion and time series CT images for predicting the benefits from anti-HER2 targeted therapy in stage IV gastric cancer.

OBJECTIVE: To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy. METHODS: A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F). RESULTS: In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728-1.000) and 0.809 (0.561-1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510-1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p < 0.05). CONCLUSION: The Nomo-LDLM-2F score derived from multi-lesion and time series CT images holds promise for the effective readout of OS probability in patients with HER2-positive stage IV GC receiving anti-HER2 therapy. CRITICAL RELEVANCE STATEMENT: The deep learning model using baseline and early follow-up CT images aims to predict OS in patients with stage IV gastric cancer receiving anti-HER2 targeted therapy. This model highlights the spatiotemporal heterogeneity of stage IV GC, assisting clinicians in the early evaluation of the efficacy of anti-HER2 therapy. KEY POINTS: • Multi-lesion and time series model revealed the spatiotemporal heterogeneity in anti-HER2 therapy. • The Nomo-LDLM-2F score was a valuable prognostic marker for anti-HER2 therapy. • CT-based deep learning model incorporating time-series tumor markers improved performance.

Dual-emission carbon dots for ratiometric fluorescence sensing of thiabendazole in fruits.

Quantitative determination of pesticides in fruits and vegetables is essential for human healths. Herein, a new dual-emission carbon dots with high fluorescence stability at a pH range of 4-10 and a temperature range of 0-60 °C was synthesized. And a novel ratiometric fluorescence probe was proposed to detect thiabendazole (TBZ) residue with a wide linear range (0-1000 µM) and low detection limit (0.15 µM). The emission at 512 nm exhibited a special "turn-off" fluorescence sensing of TBZ due to internal filter effect, while that at 361 nm barely changed and worked as reference. Furthermore, the ratiometric fluorescence strategy was successfully applied for determining TBZ in fruits with good recoveries (96.73%-111.17 %, 93.29%-120.78 % and 96.28%-100.57 %, respectively). Notably, the constructed ratiometric fluorescence probe had comparable accuracy to HPLC in detecting unknown concentrations of TBZ in pear juice, demonstrating dual-emission carbon dots possess wide and promising applicability for fluorescence sensing pesticides in the future.

Synthesis, properties and mechanism of carbon dots-based nano-antibacterial materials.

Antibiotics play an important role in the treatment of diseases, but bacterial resistance caused by their widespread and unreasonable use has become an urgent problem in clinical treatment. With the rapid advancement of nanoscience and nanotechnology, the development of nanomedicine has been transformed into a new approach to the problem of bacterial resistance. As a new type of carbon-based nanomaterial, carbon dots (CDs) have attracted the interest of antibacterial researchers due to their ease of preparation, amphiphilicity, facile surface functionalization, and excellent optical properties, among other properties. This article reviewed the synthesis methods and properties of various CDs and their composites in order to highlight the advancements in the field of CDs-based antibacterial agents. Then we focused on the relationship between the principal properties of CDs and the antibacterial mechanism, including the following: (1) the physical damage caused by the small size, amphiphilicity, and surface charge of CDs. (2) Photogenerated electron transfer characteristics of CDs that produce reactive oxygen species (ROS) in themselves or in other compounds. The ability of ROS to oxidize can lead to the lipid peroxidation of cell membranes, as well as damage proteins and DNA. (3) The nano-enzyme properties of CDs can catalyze reactions that generate ROS. (4) Synergistic antibacterial effect of CDs and antibiotics or other nanocomposites. Finally, we look forward to the challenges that CDs-based nanocomposites face in practical antibacterial applications and propose corresponding solutions to further expand the application potential of nanomaterials in the treatment of infectious diseases, particularly drug-resistant bacterial infections.

Effects of a combination of lauric acid monoglyceride and cinnamaldehyde on growth performance, gut morphology, and gut microbiota of yellow-feathered broilers.

A total of 480 one-day-old male yellow-feathered broilers were randomly divided into 4 groups with 6 replicates of 20 chicks per replicate. A basal diet was administered to the control group (CON), whereas CML350, CML500, and CML1000 groups were fed with basal diet supplemented with 350, 500, and 1,000 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex, respectively. However, adding 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex improved weight gain (P < 0.01), enhanced intestinal morphology, increased serum total protein and albumin content, and total antioxidant capacity (P < 0.01), and significantly increased the Chao1 and Ace indices (P < 0.01), indicating an increase in the richness of the gut microbiota. At the phylum level, CML500 group reduced the abundance of Fusobacteriota at 21 d and Proteobacteria at 42 d (P < 0.01). At the genus level, CML500 group increased the abundance of Faecalibacterium and Alistipes at 42 d (P < 0.01) and decreased the abundance of Escherichia-Shigella (P < 0.01). At the species level, CML500 group reduced the abundance of Escherichia coli at 42 d (P < 0.01) and increased the abundance of Alistipes_sp_CHKCI003 at 42 d (P < 0.01). According to these results, adding 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex in feed can improve the growth performance, intestinal morphology, and gut microbiota of yellow-feathered broilers.

Associations of subcutaneous fat area and Systemic Immune-inflammation Index with survival in patients with advanced gastric cancer receiving dual PD-1 and HER2 blockade.

BACKGROUND: Systemic Immune-inflammation Index (SII) and body composition parameters are easily assessed, and can predict overall survival (OS) in various cancers, allowing early intervention. This study aimed to assess the correlation between CT-derived body composition parameters and SII and OS in patients with advanced gastric cancer receiving dual programmed death-1 (PD-1) and human epidermal growth factor receptor 2 (HER2) blockade. MATERIALS AND METHODS: This retrospective study enrolled patients with advanced gastric cancer treated with dual PD-1 and HER2 blockade from March 2019 to June 2022. We developed a deep learning model based on nnU-Net to automatically segment skeletal muscle, subcutaneous fat and visceral fat at the third lumbar level, and calculated the corresponding Skeletal Muscle Index, skeletal muscle density, subcutaneous fat area (SFA) and visceral fat area. SII was computed using the formula that total peripheral platelet count×neutrophil/lymphocyte ratio. Univariate and multivariate Cox regression analysis were used to determine the associations between SII, body composition parameters and OS. RESULTS: The automatic segmentation deep learning model was developed to efficiently segment body composition in 158 patients (0.23 s/image). Multivariate Cox analysis revealed that high SII (HR=2.49 (95% CI 1.54 to 4.01), p<0.001) and high SFA (HR=0.42 (95% CI 0.24 to 0.73), p=0.002) were independently associated with OS, whereas sarcopenia was not an independent prognostic factor for OS (HR=1.41 (95% CI 0.86 to 2.31), p=0.173). In further analysis, patients with high SII and low SFA had worse long-term prognosis compared with those with low SII and high SFA (HR=8.19 (95% CI 3.91 to 17.16), p<0.001). CONCLUSION: Pretreatment SFA and SII were significantly associated with OS in patients with advanced gastric cancer. A comprehensive analysis of SII and SFA may improve the prognostic stratification of patients with gastric cancer receiving dual PD-1 and HER2 blockade.

Smartphone-assisted miniature device based on nitrogen and sulfur co-doped carbon dots for point-of-care testing of tetracycline.

A miniature device was design for the point-of-care testing (POCT) of tetracycline (TC) including a ratio fluorescence test strip, a sample slot, a UV lamp and a smartphone. The nitrogen and sulfur co-doped carbon dots (N, S-CDs) and Eu3+ were dropped onto the filter paper to construct the ratio fluorescence test strips for the specific detection of TC. Under the excitation at 390 nm, the fluorescence emission of N, S-CDs at 530 nm decreases through inner filter effect (IEF) after addition of Eu3+. When the further addition of TC, the emission of N, S-CDs at 530 nm kept unchanged while the emission of Eu3+ at 616 nm was obviously enhanced for the antenna effect (AE) between Eu3+ and TC. The ratio changes of the two-fluorescence emission realized the quantitative detection of TC. In addition, the test strips with different concentrations of TC showed different fluorescence color from green to red under a 365 nm UV lamp. The miniature device was designed as a fluorescence photo reader with the merits of the powerful functions of smartphones and the portability of test strips. The smartphone camera takes a fluorescent color image of the test strips and the photos are recognized by a color recognizer on the smartphone to obtain RGB (red-greenblue) values which reflect the concentrations of the analytes. Therefore, we established a fast, sensitive and efficient POCT of TC. In particular, the proposed nanomaterial-based POCT platform will open a new route towards the development of ratio fluorescence probe for TC analysis for environment samples.

Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment.

A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4+FoxP3-PD-L1+, CD8+PD-1-LAG3-, and CD68+STING+ cells and the spatial organisation of CD8+PD-1+LAG3- T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.

CT-based delta radiomics in predicting the prognosis of stage IV gastric cancer to immune checkpoint inhibitors.

Introduction: To explore the prognostic value of CT-based delta radiomics in predicting the prognosis of patients with stage IV gastric cancer treated with immune checkpoint inhibitors (ICI). Materials and methods: Forty-two patients with stage IV gastric cancer, who had received ICI monotherapy, were enrolled in this retrospective study. Baseline and first follow-up CT scans were analyzed. Intratumoral and peritumoral regions of interest (ROI) were contoured, enabling the extraction of 192 features from each ROI. The intraclass correlation coefficients were used to select features with high stability. The least absolute shrinkage and selection operator was used to select features with high weights for predicting patient prognosis. Kaplan-Meier analysis and log-rank test were performed to explore the association between features and progression free survival (PFS). Cox regression analyses were used to identify predictors for PFS. The C-index was used to assess the prediction performance of features. Results: Two radiomics features of ΔVintra_ZV and postVperi_Sphericity were identified from intratumoral and peritumoral regions, respectively. The Kaplan-Meier analysis revealed significant differences in PFS between patients with low and high feature value (ΔVintra_ZV: P=0.000; postVperi_Sphericity: P=0.012), and the multivariable cox analysis demonstrated that ΔVintra_ZV was independent predictor for PFS (HR, 1.911; 95% CI: 1.163-3.142; P=0.011), with C-index of 0.705. Conclusions: Based on CT scans at baseline and first follow-up, the delta radiomics features could efficiently predict the PFS of gastric cancer patients treated with ICI therapy.

Utility of ForenSeq™ DNA Signature Prep Kit in the research of pairwise 2nd-degree kinship identification.

The scope of forensic kinship analysis is being extended to more distant or complex relationships. However, current methods and standards in this field do not meet the needs of casework. The next-generation sequencing (NGS) technology may hold an advantage in this field to traditional methods due to its strong power to get much more genetic information. To evaluate the effectiveness of NGS to identify the 2nd-degree kinship pairs, DNA samples of 227 individuals from 49 Hebei Han pedigrees were tested by Goldeneye™ 20A kit using capillary electrophoresis (CE) to confirm the relationships within each pedigree, and those of 111 individuals within 97 confirmed grandparent-grandchild or avuncular pairs were analyzed by ForenSeq™ DNA Signature Prep Kit using MiSeq® FGx™ DNA sequencing platform. We calculated the likelihood ratio (LR) based on ITO method and the identical by state (IBS) score of 97 kinship pairs and compared with those of 97 unrelated pairs. According to the results summarized and analyzed by Fisher discriminant analysis and leave-one-out cross-validation (LOOCV) method, ITO method showed higher accuracy than IBS method, even with less information. Therefore, we proposed a recommendation of the thresholds for pairwise 2nd-degree kinship identification for Hebei Han population based on ITO method. When using ITO method based on 94 SNPs and the length information of 27 autosomal STRs, cumulative likelihood ratio (CLR) > 1 and CLR < 0.1 are recommended as the thresholds of confirming and excluding, respectively. The accuracy applying such thresholds is greater than 95%, indicating the promising application value of NGS in this field and providing a direction for further kinship identification strategy selection. Further studies are needed to get the population genetic data of loci contained in the kit based on all sequence information including flanking regions to make full use of the NGS data to improve the accuracy of kinship analysis.

Low heart deceleration capacity imply higher atrial fibrillation-free rate after ablation.

How deceleration capacity (DC) and acceleration capacity (AC) of heart rate associated with atrial fibrillation (AF) and ablation is still not clear. The dynamic changes of AC, DC and conventional heart rate variability (HRV) parameters were characterized in 154 subjects before circumferential pulmonary veins isolation (CPVI) and three days, 3 months and 6 months after CPVI. The DCs of the recurrent group decreased significantly at each time point after CPVI; the DCs of the recurrence-free group before CPVI and three days, 3 months and 6 months after CPVI were 7.06 ± 1.77, 3.79 ± 1.18, 4.22 ± 1.96 and 3.97 ± 0.98 ms respectively, which also decreased significantly at each time point and were significantly lower than these of recurrent group. Conversely, the AC of recurrent and recurrence-free groups increased significantly at each time point after CPVI; the ACs of recurrence-fee group were significantly higher than these of recurrent group at each time point. No stable difference trend of HRV parameters was found between two groups. Further Kaplan-Meier analysis showed that DC < 4.8 ms or AC ≥ -5.1 ms displayed significant higher recurrence-free rates. In conclusion, high AC and low DC imply higher AF-free rate after ablation.

SUMO modification of NZFP mediates transcriptional repression through TBP binding.

The negatively regulating zinc finger protein (NZFP) is an essential transcription repressor required for early development during gastrulation in Xenopus laevis. In this study, we found that NZFP interacts with the small ubiquitin-like modifier (SUMO) conjugation E2 enzyme, Ubc9, and contains three putative SUMO conjugation sites. Studies with NZFP mutants containing mutations at the putative SUMO conjugation sites showed that these sites were able to be modified independently with SUMO. NZFP was found to be localized in the same nuclear bodies with SUMO-1. However, sumoylation of NZFP did not play a role either in the translocation of NZFP into the nucleus or on nuclear body formation. While wild type NZFP showed significant transcriptional repression, SUMO-conjugation site mutants manifested a decrease in transcriptional repression activity which is reversely proportional to the amount of sumoylation. The sumoylation defective mutant lost its TBP binding activity, while wild type NZFP interacted with TBP and inhibited transcription complex formation. These results strongly suggest that the sumoylation of NZFP facilitates NZFP to bind to TBP and the NZFP/TBP complex then represses the transcription of the target gene by inhibiting basal transcription complex formation.