Search

Background The aim of this study is to provide a comprehensive understanding of the current landscape of artificial intelligence (AI) for cancer clinical trial enrollment and its predictive accuracy in identifying eligible patients for inclusion in such trials. Methods Databases of PubMed, Embase, and Cochrane CENTRAL were searched until June 2022. Articles were included if they reported on AI actively being used in the clinical trial enrollment process. Narrative synthesis was conducted among all extracted data: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. For studies where the 2x2 contingency table could be calculated or supplied by authors, a meta-analysis to calculate summary statistics was conducted using the hierarchical summary receiver operating characteristics curve model. Results Ten articles reporting on more than 50 000 patients in 19 datasets were included. Accuracy, sensitivity, and specificity exceeded 80% in all but 1 dataset. Positive predictive value exceeded 80% in 5 of 17 datasets. Negative predictive value exceeded 80% in all datasets. Summary sensitivity was 90.5% (95% confidence interval [CI] = 70.9% to 97.4%); summary specificity was 99.3% (95% CI = 81.8% to 99.9%). Conclusions AI demonstrated comparable, if not superior, performance to manual screening for patient enrollment into cancer clinical trials. As well, AI is highly efficient, requiring less time and human resources to screen patients. AI should be further investigated and implemented for patient recruitment into cancer clinical trials. Future research should validate the use of AI for clinical trials enrollment in less resource-rich regions and ensure broad inclusion for generalizability to all sexes, ages, and ethnicities.

Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AG and HIST1H2BK. Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.

In the quality analysis of contemporary industrial production of praseodymium-neodymium (Pr-Nd) alloys, the amount of carbon content is mainly determined using chemical analysis methods. To overcome the shortcomings of the long durations and high costs of quality inspection cycles, this study proposes a non-destructive model for determining the carbon content of Pr-Nd alloys using acoustic emission signals collected using a mel frequency cepstral coefficient (MFCC) long short-term memory (LSTM) network (MFCC-LSTM) model and a data acquisition system. The MFCC ensures accurate signal feature extraction and data dimensionality reduction and the LSTM enables learning of the extracted features. The recognition rate of the MFCC-LSTM model reaches up to 97.53%, which can satisfy the quality inspection requirements for the industrial production of Pr-Nd alloys. In model evaluation, the receiver operating characteristic (ROC) curve shows good performance indices, indicating that the model is robust. Real-time verification of the model shows that the proposed method greatly shortens the time of each quality inspection link; the quality inspection time for a single piece of Pr-Nd alloy is only 0.3-0.65 s, which is a good real-time parameter.

The Dragonfly Algorithm (DA) is a novel swarm intelligence algorithm with some positive applications in recent years. The algorithm simulates the basic survival ability of dragonflies to evade predators and capture prey in natural environment. The original DA algorithm converges too fast, and it is easy to fall into the local optimum, which causes the search to stagnate and the algorithm effect is not ideal. Based on above, a collaborative evolutionary dragonfly algorithm (CDA) with multi-group strategy is proposed in this paper. It uses multi-group strategy and Cauchy mutation to jointly improve the convergence speed and accuracy of the original algorithm. Image segmentation is an essential aspect of computer graphics and image processing. It has become increasingly important. This paper uses threshold technology based on the CDA algorithm to find the optimal index value under different threshold conditions. The experimental results have demonstrated that the CDA is highly competitive in terms of convergence speed and convergence accuracy DA algorithm, and CDA also performs excellent advantages in graphic segmentation experiments. &nbsp

Oxidative stress results in the production of excess reactive oxygen species (ROS) and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative disorders such as Alzheimer's disease (AD). A recent study confirmed that magnesium had an inhibitory effect against oxidative stress-related malondialdehydeTo explore the neuroprotective effect of MgT against oxidative stress injuryAβMgT exhibits neuroprotective effects against oxidative stress and hippocampal neuronal apoptosis in Aβ

Table S1: Patient Radiotherapy Information and Multivariate Analysis.

Table S1: Patient Radiotherapy Information and Multivariate Analysis. Figure S1: Workflow of evaluation of T cell receptor (TCR) rearrangement and ESTIMATE immune score from RNA-sequencing data, and the expression of tumor-infiltrating lymphocytes (TILs) in NPC patients. Figure S2: The correlation of ESTIMATE immune score with rearranged TCR reads and CD8+ TILs. Figure S3: The correlation of CIBERSORT and TIMER 2.0 with rearranged TCR reads and CD8+ TILs. Figure S4: The distribution of TILs in NPC samples. Figure S5: Clinical impact of CD8+ TILs in the combined cohort of NPC patients.

Purpose:Tumor-infiltrating lymphocytes (TIL) are immune cell populations found within tumors, critical in the antigen-specific host immune response. In this study, we aimed to elucidate the prognostic significance of CD3+, CD4+, and CD8+ TILs in nasopharyngeal cancer (NPC).Experimental Design:Immune cell infiltration was quantified in NPC samples (n = 50) using RNA-sequencing (RNA-seq) data based on rearranged T-cell receptor (TCR) reads and the Estimation of Stromal and Immune cells in malignant tumors using expression data (ESTIMATE) immune score tool. The differential abundances of TIL subset populations were also characterized through IHC staining of formalin-fixed, paraffin-embedded samples from a training cohort (n = 35), which was a subset of the RNA-seq cohort (n = 50).Results:In the RNA-seq cohort, patients with higher rearranged TCR reads experienced superior 5- and 10-year overall survival (OS; P < 0.001), and disease-free survival (DFS; P < 0.001). Similarly, patients with higher ESTIMATE immune scores experienced superior 5- and 10-year OS (P = 0.024) and DFS (P = 0.007). In the training cohort, high abundances of CD8+ TILs were significantly associated with improved 5- and 10-year OS (P = 0.003) and DFS (P = 0.005). These findings were corroborated in an independent validation cohort (n = 84), and combined analysis of the training and validation cohorts [n = 119 (35+84)], which further demonstrated improved 5- and 10-year survival in terms of locoregional control (P < 0.001) and distant metastasis (P = 0.03).Conclusions:Taken together, our study highlights the prognostic value of CD8+ TILs in NPC, and the potential of future investigations into cellular-based immunotherapies employing CD8+ lymphocytes.

Supplementary Figure 3 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Supplementary Figure from Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

Supplementary Figure 2 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

PDF file - 53K, Survival analysis of the 88 analyzed OPC patients

Supplementary Data from Efficacy of Systemically Administered Mutant Vesicular Stomatitis Virus (VSVΔ51) Combined with Radiation for Nasopharyngeal Carcinoma

Purpose: The objective of this study is to investigate the significance of microRNAs (miRNA) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: A global miRNA profiling was done on 51 formalin-fixed archival HNSCC samples using quantitative reverse transcription-PCR approach, correlated with patients' clinical parameters. Functional characterization of HNSCC-associated miRNAs was conducted on three HNSCC cell lines. Cell viability and proliferation were investigated using MTS and clonogenic assays, respectively; cell cycle analyses were assessed using flow cytometry.Results: Thirty-eight of the 117 (33%) consistently detected miRNAs were significantly differentially expressed between malignant versus normal tissues. Concordant with previous reports, overexpression of miR-21, miR-155, let-7i, and miR-142-3p and underexpression of miR-125b and miR-375 were detected. Upregulation of miR-423, miR-106b, miR-20a, and miR-16 as well as downregulation of miR-10a were newly observed. Exogenous overexpression of miR-375 in HNSCC cell lines reduced proliferation and clonogenicity and increased cells in sub-G1. Similar cellular effects were observed in knockdown studies of the miR-106b-25 cluster but with accumulation of cells in G1 arrest. No major difference was detected in miRNA profiles among laryngeal, oropharyngeal, or hypopharyngeal cancers. miR-451 was found to be the only significantly overexpressed miRNA by 4.7-fold between nonrelapsed and relapsed patients.Conclusion: We have identified a group of aberrantly expressed miRNAs in HNSCC and showed that underexpression of miR-375 and overexpression of miR-106b-25 cluster might play oncogenic roles in this disease. Further detailed examinations of miRNAs will provide opportunities to dissect the complex molecular abnormalities driving HNSCC progression. Clin Cancer Res; 16(4); 1129–39

PDF file - 31K, The list of the aberrantly-expressed miRNAs between OPC and normals

PDF file - 136K, Profile of studies used in this meta-analysis. Of the 51 original articles included in this report, 49 are shown here: two were excluded from this table as they did not contribute to any of the main analyses (case-only). Contribution to aims 1-3 are indicated by √ in initiation of carcinogenesis, progression of disease, and overall risk of cervical cancer, respectively.

PDF file - 27K, MiRNAs associated with p16 in OPCs samples

PDF file - 71K

Purpose: Despite recent improvements in local control of head and neck cancers (HNC), distant metastasis remains a major cause of death. Hence, further understanding of HNC biology, and in particular, the genes/pathways driving metastasis is essential to improve outcome.Experimental Design: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and metadherin (MTDH) in HNC patient samples. Targets of miR-375 were confirmed using qRT-PCR, Western blot analysis, and luciferase assays. Phenotypic effects of miR-375 reexpression and MTDH knockdown were assessed using viability (MTS), clonogenic survival, cell migration/invasion, as well as in vivo tumor formation assays. The prognostic significance of miR-375 or MTDH in nasopharyngeal carcinoma (NPC) was determined by comparing low versus high expression groups.Results: MiR-375 expression was significantly reduced (P = 0.01), and conversely, MTDH was significantly increased (P = 0.0001) in NPC samples. qRT-PCR, Western blots, and luciferase assays corroborated MTDH as a target of miR-375. Reexpression of miR-375 and siRNA knockdown of MTDH both decreased cell viability and clonogenic survival, cell migration/invasion, as well as in vivo tumor formation. NPC patients whose tumors expressed high levels of MTDH experienced significantly lower survival and, in particular, higher distant relapse rates (5-year distant relapse rates: 26% vs. 5%; P = 0.005).Conclusions: Dysregulation of miR-375 and MTDH may represent an important oncogenic pathway driving human HNC progression, particularly distant metastases, which is now emerging as a major cause of death for HNC patients. Hence, targeting this pathway could potentially be a novel therapeutic strategy by which HNC patient outcome could be improved. Clin Cancer Res; 17(24); 7539–50. ©2011 AACR.

Supplementary Figure 1 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Purpose: Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck region that is associated with EBV latency. Curative treatments for NPC achieve modest survival rates, underscoring a need to develop novel therapies. We evaluated the therapeutic potential of a mutant vesicular stomatitis virus (VSVΔ51) as single treatment modality or in combination with ionizing radiation (RT) in NPC.Experimental Design: MTS assay was used to assess cell viability in vitro; apoptosis was measured using propidium iodide staining and caspase activation. In vivo experiments were conducted using tumor-bearing nude mice with or without local RT (4 Gy). Apoptosis was assessed in excised tumor sections with terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining.Results: Our data showed that NPC cells are exquisitely sensitive to VSVΔ51 oncolysis, which correlated with the presence of EBV. Efficacy of VSVΔ51 against NPC cells was further augmented when combined with RT. A single systemic injection of VSVΔ51 achieved 50% survival in treated mice, which increased to 83% when combined with local tumor RT. In addition to induction of apoptosis, an antiangiogenic effect of VSVΔ51 was observed in vivo, suggesting a novel tumoricidal mechanism for VSVΔ51. This virus also prevented growth of NPC sphere-forming cells in vitro, showing potential utility in targeting NPC-initiating cells.Conclusions: Our data represent the first report showing that EBV-positive NPC cells are exquisitely sensitive to VSVΔ51 oncolysis and documenting the successful utilization of this combinatorial regimen as a novel curative therapeutic strategy for NPC.

Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer.Experimental Design: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values.Results: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed.Conclusion: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.

Supplementary Figure Legends 1-3 from Gene Expression Profiling in Cervical Cancer: An Exploration of Intratumor Heterogeneity

Supplementary Data from Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

PDF file - 65K, Comparison of differential miRNA expression levels by p16 IHC and HPV16 ISH

PDF file - 31K, Comparison of miRNA expression between tumor and normal samples

Purpose:Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation.Experimental Design:We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I–IVA human papillomavirus–negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls.Results:CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (r > 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5; P = 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples.Conclusions:Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.

PDF file - 108K, Supplementary Figure 1. Funnel plot for included studies that evaluated overall risk. The included studies were summarized in Supplementary Table 1. Supplementary Figure 2. Forest plot with OR for risk of cervical cancer compared to normal controls. OR and heterogeneity measures are shown for each subset as a subtotal A) HPV positive subset; B) HPV negative subset and for the pooled analysis as a total. Weights of individual studies are represented by black boxes. Diamonds represent weighted OR with 95% confidence limits. Recessive model shown.