The application value of a vendor-specific deep learning image reconstruction algorithm in "triple low" head and neck computed tomography angiography.

Background: Head and neck computed tomography angiography (CTA) technology has become the noninvasive imaging method of choice for the diagnosis and long-term follow-up of vascular lesions of the head and neck. However, issues of radiation safety and contrast nephropathy associated with CTA examinations remain concerns. In recent years, deep learning image reconstruction (DLIR) algorithms have been increasingly used in clinical studies, demonstrating their potential for dose optimization. This study aimed to investigate the value of using a DLIR algorithm to reduce radiation and contrast doses in head and neck CTA. Methods: A total of 100 patients were prospectively enrolled and randomly divided into two groups. Group A (50 patients) consisted of those who underwent 70-kVp CTA with a low contrast volume and injection rate and who were classified according to the reconstruction algorithm into subgroups A1 [DLIR at high weighting (DLIR-H)], A2 [DLIR at low weighting (DLIR-L)], and A3 [volume-based adaptive statistical iterative reconstruction with 50% weighting (ASIR-V50%)]. Meanwhile, group B (50 patients) consisted of those who underwent standard radiation and contrast doses at 100 kVp with ASIR-V50% reconstruction. The computed tomography (CT) attenuation, background noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective image quality score (SIQS) were statistically compared for several vessels among the four groups. Results: Group A showed significant reductions in contrast dosage, injection rate, and radiation dose of 36.09%, 20.88%, and 47.80%, respectively, compared to group B (all P<0.001). The four groups differed significantly in terms of background noise (all P<0.05) with group A1 having the lowest value. Group A1 also had significantly higher SNR and CNR values compared to group B in all vessels (all P<0.05) except the M1 of the middle cerebral artery for the SNR. Group A1 also had the highest SIQS, followed by the A2, B, and A3 groups. The SIQS showed good agreement between the two reviewers in all groups, with κ values between 0.88 and 1. Conclusions: Compared to the standard-dose protocol using 100 kVp and ASIR-V50%, a protocol of 70 kVp combined with DLIR-H significantly reduces the radiation dose, contrast dose, and injection rate in head and neck CTA while still significantly improving image quality for patients with a standard body size.

Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients' clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan-Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.

Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis.

Immune checkpoint blockade (ICB) exhibits considerable benefits in malignancies, but its overall response rate is limited. Previous studies have shown that sphingosine kinases (SPHKs) are critical in the tumor microenvironment (TME), but their role in immunotherapy is unclear. We performed integrative analyses including bioinformatics analysis, functional study, and clinical validation to investigate the role of SPHK1 in tumor immunity. Functionally, we demonstrated that the inhibition of SPHK1 significantly suppressed tumor growth by promoting antitumor immunity in immunocompetent melanoma mouse models and tumor T-cell cocultures. A mechanistic analysis revealed that MTA3 functions as the downstream target of SPHK1 in transcriptionally regulating tumor PD-L1. Preclinically, we found that anti-PD-1 monoclonal antibody (mAb) treatment significantly rescued tumor SPHK1 overexpression or tumor MTA3 overexpression-mediated immune evasion. Significantly, we identified SPHK1 and MTA3 as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients. Our findings revealed a novel role for SPHK1 in tumor evasion mediated by regulating the MTA3-PD-L1 axis, identified SPHK1 and MTA3 as predictors for assessing the efficacy of PD-1 mAb treatment, and provided a therapeutic possibility for the treatment of melanoma patients.

Characterization of Immune-Related Alternative Polyadenylation Events in Cancer Immunotherapy.

Alternative polyadenylation (APA) is an important posttranscriptional modification commonly involved in tumor development. However, the functional roles of APA in tumor immunity remain largely unknown. Here, we performed an in-depth analysis of the 3'UTR usage of protein-coding genes and tumor immune response in 10,303 tumor samples across 31 cancer types to develop the immune-related APA event (ImmAPA) score pipeline, an integrated algorithm to characterize the regulatory landscape of APA events in cancer immunity-related pathways. Tumor-specific ImmAPAs that strongly correlate with immune cell infiltration and immune checkpoint blockade (ICB) treatment-related biomarkers were identified. Among these ImmAPAs, the top-ranking COL1A1 3'UTR usage was strongly associated with worse prognosis and tumor immune evasion. Furthermore, a machine learning approach to construct an ICB-related ImmAPA score model predicted immunotherapy efficacy. Overall, the characterization of immune-related APA that corresponds to tumor progression and tumor immunity highlights the clinical utility of APA events as potential biomarkers in cancer immunotherapy. SIGNIFICANCE: Elucidation of the landscape of immune-related alternative polyadenylation in cancer identifies alternative polyadenylation events that may play a role in immune modulation and immunotherapy efficacy.