In situ vaccination followed by intramuscular poly-ICLC injections for the treatment of hepatocellular carcinoma in mouse models.

The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8+ T cells in two syngeneic mouse models of HCC. Depletion of CD8+ T cells attenuated the antitumor effect. An IFN-γ enzyme-linked immunospot of purified tumoral CD8+ T cells revealed a significant proportion of tumor-specific T cells. Finally, the sequential poly-ICLC therapy induced abscopal effects in two dual-tumor models. This study provides evidence that the sequential poly-ICLC therapy significantly increased infiltration of tumor-specific CD8+ T cells in the tumors and induced CD8+ T cell-dependent inhibition of tumor growth, as well as abscopal effects.

Neoantigen vaccination augments antitumor effects of anti-PD-1 on mouse hepatocellular carcinoma.

Immune checkpoint inhibitors are groundbreaking resources for cancer therapy. However, only a few patients with hepatocellular carcinoma (HCC) have shown positive responses to anti-PD-1 therapy. Neoantigens are sequence-altered proteins resulting from somatic mutations in cancer. This study identified the neoantigens of Hep-55.1C and Dt81 Hepa1-6 HCCs by comparing their whole exome sequences with those of a normal C57BL/6 mouse liver. Immunogenic long peptides were pooled as peptide vaccines. The vaccination elicited tumor-reactive immune responses in C57BL/6 mice, as demonstrated by IFN-γ ELISPOT and an in vitro killing assay of splenocytes. In the treatment of three mouse HCC models, combined neoantigen vaccination and anti-PD-1 resulted in more significant tumor regression than monotherapies. Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8+ T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8+ T cells in the combination group. These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC.

Chat Analysis Triage Tool: Differentiating contact-driven vs. fantasy-driven child sex offenders.

Investigating crimes against children, specifically sexual solicitations, are complicated because not all offenders are contact-driven, meaning they want to meet the minor for sex in the physical world; instead, some offenders are fantasy-driven, in that they are more interested in cybersex and role-play. In addition, the sheer volume of cases involving the online sexual solicitation of minors makes it difficult for law enforcement to determine whether an offender is contact-driven vs. fantasy-driven. However, research shows that there are language-based differences between minors and contact-driven offenders vs. fantasy driven-offenders. Thus, we developed the Chat Analysis Triage Tool (CATT), a forensically sound investigative tool that, based on natural language processing methods, analyzes and compares chats between minors and contact-driven vs. non-contract driven offenders. Using an SVM classifier, we were successful in differentiating the classes based on character trigrams. In a matter of seconds, the existing algorithms provide an identification of an offender's risk level based on the likelihood of contact offending as inferred from the model, which assists law enforcement in their ability to triage and prioritize cases involving the sexual solicitation of minors.

Fast computation of Hessian-based enhancement filters for medical images.

This paper presents a method for fast computation of Hessian-based enhancement filters, whose conditions for identifying particular structures in medical images are associated only with the signs of Hessian eigenvalues. The computational costs of Hessian-based enhancement filters come mainly from the computation of Hessian eigenvalues corresponding to image elements to obtain filter responses, because computing eigenvalues of a matrix requires substantial computational effort. High computational cost has become a challenge in the application of Hessian-based enhancement filters. Using a property of the characteristic polynomial coefficients of a matrix and the well-known Routh-Hurwitz criterion in control engineering, it is shown that under certain conditions, the response of a Hessian-based enhancement filter to an image element can be obtained without having to compute Hessian eigenvalues. The computational cost can thus be reduced. Experimental results on several medical images show that the method proposed in this paper can reduce significantly the number of computations of Hessian eigenvalues and the processing times of images. The percentage reductions of the number of computations of Hessian eigenvalues for enhancing blob- and tubular-like structures in two-dimensional images are approximately 90% and 65%, respectively. For enhancing blob-, tubular-, and plane-like structures in three-dimensional images, the reductions are approximately 97%, 75%, and 12%, respectively. For the processing times, the percentage reductions for enhancing blob- and tubular-like structures in two-dimensional images are approximately 31% and 7.5%, respectively. The reductions for enhancing blob-, tubular-, and plane-like structures in three-dimensional images are approximately 68%, 55%, and 3%, respectively.