Search Results (11)

Leveraging the complementary strengths of handcrafted radiomics and data-driven deep learning, this work develops and rigorously benchmarks three modeling streams (Models A, B and C) for pancreatic ductal adenocarcinoma (PDAC) detection on multiphase abdominal Computed Tomography (CT) scans. Model A distills hundreds of PyRadiomics descriptors to sixteen interpretable features that feed a gradient-boosted machine learning model, achieving discrimination (external AUC ≈ 0.99) with excellent calibration. Model B adopts a 3-D CBAM-ResNet-18 trained under weighted cross-entropy and mixed precision; although less accurate in isolation, it yields volumetric Grad-CAM maps that localize the tumor and provide explainability. Model C explores two fusion strategies that merge radiomics and deep embeddings: (i) a two-stage “frozen-stream” variant that locks both feature extractors and learns only a lightweight gating block plus classifier, and (ii) a full end-to-end version that allows the CNN’s adaptor layer to co-train with the fusion head. The frozen approach surpasses the single stream, whereas the end-to-end model reports external AUC of 0.987, balanced sensitivity/specificity above 0.93, and a Brier score below 0.05, while preserving clear Grad-CAM alignment with radiologist-drawn masks. Results demonstrate that a carefully engineered deep-radiomic fusion pipeline can deliver accurate, well-calibrated and interpretable PDAC triage directly from routine CT. Our contributions include a stability-verified 16-feature radiomic signature, a novel deep-radiomic fusion design that improves robustness and interpretability across vendors and a fully guideline-aligned, openly released pipeline for reproducible PDAC detection on routine CT. Full article

Traumatic brain injury (TBI) leads to persistent pro-inflammatory microglial activation implicated in neurodegeneration. Idebenone, a coenzyme Q10 analogue that interacts with both mitochondria and the tyrosine kinase adaptor SHC1, inhibits aspects of microglial activation in vitro. We used the NanoString Neuropathology Panel to test the hypothesis that idebenone post-treatment mitigates TBI-pathology-associated acute gene expression changes by moderating the pro-inflammatory microglial response to injury. Controlled cortical impact to adult male mice increased the microglial activation signature in the peri-lesional cortex at 24 h post-TBI. Unexpectedly, several microglial signature genes upregulated by TBI were further increased by post-injury idebenone administration. However, idebenone significantly attenuated TBI-mediated perturbations to gene expression associated with behavior, particularly in the gene ontology–biological process (GO:BP) pathways “ephrin receptor signaling” and “dopamine metabolic process”. Gene co-expression analysis correlated levels of microglial complement component 1q (C1q) and the neurotrophin receptor gene Ntrk1 to large (>3-fold) TBI-induced decreases in dopamine receptor genes Drd1 and Drd2 that were mitigated by idebenone treatment. Bioinformatics analysis identified SUZ12 as a candidate transcriptional regulator of idebenone-modified gene expression changes. Overall, the results suggest that idebenone may enhance TBI-induced microglial number within the first 24 h of TBI and identify ephrin-A and dopamine signaling as novel idebenone targets. Full article

Cross-chain transaction technologies have greatly promoted the scalability of cryptocurrencies, which then facilitates the development of Metaverse applications. However, existing solutions rely heavily on centralized middleware (notary) or smart contracts. These schemes lack privacy considerations, and users’ cross-chain transactions are easy to master by other parties. Some signature-based payment schemes have good privacy but do not support multi-party cross-chain protocols or rely heavily on some time assumptions. The uncertainty of user behavior makes it difficult to design a secure multi-party cross-chain protocol. To solve these problems, we investigate how to design a secure multi-party cross-chain transaction protocol with offline tolerance. We propose a new signature algorithm called the pre-adaptor signature scheme, an extension of the adaptor signature scheme. The pre-adaptor signature scheme combines the multi-signature and adaptor signature schemes, which can realize the secret transmission channel between multiple parties. To provide offline tolerance, we encode our protocol into the P2SH script. Our protocol provides better privacy due to no dependence on smart contracts. The performance evaluation was conducted with ten participants. For each participant of our cross-chain protocol, the initialization and execution process can be performed in 3 milliseconds and with 6 k bytes of communication overhead at most. The cost increases linearly with the increase in the number of participants. Full article

Adaptor signature is a variant of digital signatures and useful for fair excheng in financial applications such as cryptocurrencies, to name a few, off-chain transaction protocols, atomic swaps and other privacy-enhancing mechanisms. However, similar to normal digital signatures, an adaptor signature also suffers from the loss of the secret key and single-point failure, which is insufficient in practice. In this paper, we address this constraint by introducing two new concepts as enhancements: multi-adaptor signatures and threshold adaptor signatures. First, we propose the formal security models for multi-adaptor signature and threshold adaptor signature. Then, we present specific schemes for these two primitives based on the commonly used blockchain signature scheme Schnorr and the post-quantum signature scheme Dilithium, respectively. Furthermore, we provide security proofs for these four schemes. Finally, we demonstrate interesting applications for blockchains, such as oracle-based conditional payment and n to n atomic swap. Full article

Signaling threshold regulating transmembrane adaptor 1 (SIT1) encodes a disulfide-linked homodimeric lymphocyte-specific glycoprotein involved in immune cell activation. However, the relationship between SIT1 and the prognosis of skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes remains elusive. Here, we first compared the differences in SIT1 expression levels between SKCM tissues and adjacent normal tissues. Next, we found that the immune cell infiltration levels and signature pattern of immune infiltration were positively associated with the SIT1 gene mRNA levels. TCGA_SKCM RNA-seq data unveiled that the SIT1 upregulated several immune-associated signaling pathways in GSEA analysis. The high expression of SIT1 was closely related to improved survival in patients with SKCM. A pathway enrichment analysis of SIT1-associated immunomodulators indicated the involvement of the NF-κB signaling pathways. Based on SIT1-associated immunomodulators, we built a 13-gene signature by LASSO Cox regression which served as an independent prognostic factor for the survival of melanoma patients. By using the signature risk score, we achieved a good prediction result for the immunotherapy response and survival of SKCM patients. Our findings provided evidence for SIT1’s implication in tumor immunity and survival of SKCM patients. The nominated immune signature is a promising predictive model for prognosis and immunotherapy sensitivity in SKCM patients. Full article

An adaptor signature can be viewed as a signature concealed with a secret value and, by design, any two of the trio yield the other. In a multiparty setting, an initial adaptor signature allows each party to create additional adaptor signatures without the original secret. Adaptor signatures help address scalability and interoperability issues in blockchain. They can also bring some important advantages to cryptocurrencies, such as low on-chain cost, improved transaction fungibility, and fewer limitations of a blockchain’s scripting language. In this paper, we propose a new two-party adaptor signature scheme that relies on quantum-safe hard problems in coding theory. The proposed scheme uses a hash-and-sign code-based signature scheme introduced by Debris-Alazard et al. and a code-based hard relation defined from the well-known syndrome decoding problem. To achieve all the basic properties of adaptor signatures formalized by Aumayr et al., we introduce further modifications to the aforementioned signature scheme. We also give a security analysis of our scheme and its application to the atomic swap. After providing a set of parameters for our scheme, we show that it has the smallest pre-signature size compared to existing post-quantum adaptor signatures. Full article

During latency, herpesvirus infection results in the establishment of a dormant state in which a restricted set of viral genes are expressed. Together with alterations of the viral genome, several host genes undergo epigenetic silencing during latency. These epigenetic dysregulations of cellular genes might be involved in the development of cancer. In this context, Gallid alphaherpesvirus 2 (GaHV-2), causing Marek’s disease (MD) in susceptible chicken, was shown to impair the expression of several cellular microRNAs (miRNAs). We decided to focus on gga-miR-126, a host miRNA considered a tumor suppressor through signaling pathways controlling cell proliferation. Our objectives were to analyze the cause and the impact of miR-126 silencing during GaHV-2 infection. This cellular miRNA was found to be repressed at crucial steps of the viral infection. In order to determine whether miR-126 low expression level was associated with specific epigenetic signatures, DNA methylation patterns were established in the miR-126 gene promoter. Repression was associated with hypermethylation at a CpG island located in the miR-126 host gene epidermal growth factor like-7 (EGFL-7). A strategy was developed to conditionally overexpress miR-126 and control miRNAs in transformed CD4+ T cells propagated from Marek’s disease (MD) lymphoma. This functional assay showed that miR-126 restoration specifically diminishes cell proliferation. We identified CT10 regulator of kinase (CRK), an adaptor protein dysregulated in several human malignancies, as a candidate target gene. Indeed, CRK protein levels were markedly reduced by the miR-126 restoration. Full article

Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13–14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated remarkable treatment efficacy in advanced non-small cell lung cancer (NSCLC). However, low expression of programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) wild-type NSCLCs are refractory, and only few therapeutic options exist. Currently, combination therapy with ICIs is frequently used in order to enhance the treatment response rates. Yet, this regimen is still associated with poor treatment outcome. Therefore, identification of potential therapeutic targets for this subgroup of NSCLC is strongly desired. Here, we report the distinct methylation signatures of this special subgroup. Moreover, several druggable targets and relevant drugs for targeted therapy were incidentally identified. We found hypermethylated differentially methylated regions (DMRs) in three regions (TSS200, TSS1500, and gene body) are significantly higher than hypomethylated ones. Downregulated methylated genes were found to be involved in negative regulation of immune response and T cell-mediated immunity. Moreover, expression of four methylated genes (PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), BAIAP2L2 (BAR/IMD Domain Containing Adaptor Protein 2 Like 2), NPR3 (Natriuretic Peptide Receptor 3), SNX10 (Sorting Nexin 10)) can influence patients’ prognosis. Subsequently, based on DrugBank data, NetworkAnalyst 3.0 was used for protein–drug interaction analysis of up-regulated differentially methylated genes. Protein products of nine genes were identified as potential druggable targets, of which the tumorigenic potential of XDH (Xanthine Dehydrogenase), ATIC (5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase), CA9 (Carbonic Anhydrase 9), SLC7A11 (Solute Carrier Family 7 Member 11), and GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) have been demonstrated in previous studies. Next, molecular docking and molecular dynamics simulation were performed to verify the structural basis of the therapeutic targets. It is noteworthy that the identified pemetrexed targeting ATIC has been recently approved for first-line use in combination with anti-PD1 inhibitors against lung cancer, irrespective of PD-L1 expression. In future work, a pivotal clinical study will be initiated to further validate our findings. Full article

Selective breeding can lead to genetic diversity and diverse phenotypes in farm animals. Analysis of the genomic regions under selection can provide important insights into the genetic basis of complex traits. In this study, a high-density SNP array was used for analysis of genome selection signatures in Chinese Wagyu cattle. In total, we obtained 478,903 SNPs and 24,820 no-overlap regions for |iHS| (integrated haplotype score) estimations. Under the threshold of the top 1%, 239 regions were finally identified as candidate selected regions and 162 candidate genes were found based on the UMD3.1 genome assembly. These genes were reported to be associated with fatty acids, such as Bos taurus nitric oxide synthase 1 adaptor protein (NOS1AP), Bos taurus hydroxysteroid 17-beta dehydrogenase 7 (HSD17B7), Bos taurus WD repeat domain 7 (WDR7), Bos taurus ELOVL fatty acid elongase 2 (ELOVL2), Bos taurus calpain 1 (CAPN1), Bos taurus parkin RBR E3 ubiquitin protein ligase (PRKN, also known as PARK2), Bos taurus mitogen-activated protein kinase kinase 6 (MAP2K6), meat quality, including Bos taurus ADAM metallopeptidase domain 12 (ADAM12), Bos taurus 5′-aminolevulinate synthase 1 (ALAS1), Bos taurus small integral membrane protein 13 (SMIM13) and Bos taurus potassium two pore domain channel subfamily K member 2 (KCNK2), growth, and developmental traits, such as Bos taurus insulin like growth factor 2 receptor (IGF2R), Bos taurus RAR related orphan receptor A (RORA), Bos taurus fibroblast growth factor 14 (FGF14), Bos taurus paired box 6 (PAX6) and Bos taurus LIM homeobox 6 (LHX6). In addition, we identified several genes that are associated with body size and weight, including Bos taurus sorting nexin 29 (SNX29), Bos taurus zinc finger imprinted 2 (ZIM2), Bos taurus family with sequence similarity 110 member A (FAM110A), immune system, including Bos taurus toll like receptor 9 (TLR9), Bos taurus TAFA chemokine like family member 1 (TAFA1), Bos taurus glutathione peroxidase 8 (putative) (GPX8), Bos taurus interleukin 5 (IL5), Bos taurus PR domain containing 9 (PRDM9), Bos taurus glutamate ionotropic receptor kainate type subunit 2 (GRIK2) and feed intake efficiency, Bos taurus sodium voltage-gated channel alpha subunit 9 (SCN9A), Bos taurus relaxin family peptide/INSL5 receptor 4 (RXFP4), Bos taurus RNA polymerase II associated protein 3 (RPAP3). Moreover, four GO terms of biological regulation (GO:0009987, GO:0008152) and metabolic process (GO:0003824, GO:0005488) were found based on these genes. In addition, we found that 232 candidate regions (~18 Mb) overlapped with the Quantitative trait loci (QTL)regions extracted from cattle QTLdb. Our findings imply that many genes were selected for important traits in Chinese Wagyu cattle. Moreover, these results can contribute to the understanding of the genetic basis of the studied traits during the formation of this population. Full article

c-MET pathway over-activation is the signature of malignancy acquisition or chemotherapy resistance of many cancers. We recently demonstrated that type II Testicular Germ Cell Tumours (TGCTs) express c-MET receptor. In particular, we elucidated that the non-seminoma lesions express c-MET protein at higher level, compared with the seminoma ones. In line with this observation, NTERA-2 clone D1 (NT2D1) non-seminoma cells increase their proliferation, migration and invasion in response to Hepatocyte Growth Factor (HGF). One of the well-known adaptor-proteins belonging to c-MET signaling cascade is c-Src. Activation of c-Src is related to the increase of aggressiveness of many cancers. For this reason, we focused on the role of c-Src in c-MET-triggered and HGF-dependent NT2D1 cell activities. In the present paper, we have elucidated that this adaptor-protein is involved in HGF-dependent NT2D1 cell proliferation, migration and invasion, since Src inhibitor-1 administration abrogates these responses. Despite these biological evidences western blot analyses have not revealed the increase of c-Src activation because of HGF administration. However, notably, immunofluorescence analyses revealed that cytoplasmic and membrane-associated localization of c-Src shifted to the nuclear compartment after HGF stimulation. These results shed new light in the modality of HGF-dependent c-Src recruitment, and put the basis for novel investigations on the relationship between c-Src, and TGCT aggressiveness. Full article