Aberrant expression of the tight junction protein claudin 6 (CLDN6) is a hallmark of gastric can-cer progression. Its expression is regulated by the transcription factor CREB. But in H. pylo-ri-induced gastric cancer there is no information regarding what transcription factors in-duce/upregulate the expression of CLDN6. We aimed to identify if CREB and YY1 regulate the expression of CLDN6 and the site where they bind to the promoter sequence. Bioinformatics analysis, H. pylori LPS, YY1 and CREB silencing, western blot, luciferase assays, and chromatin immunoprecipitation experiments were performed using the gastric adenocarcinoma cell line AGS. A gen reporter assay suggested that the initial 2000 bp contains the regulatory sequence as-sociated with CLDN6 transcription; the luciferase assay demonstrated three different regions with transcriptional activity, but the -901 to -1421 bp region displayed the maximal transcrip-tional activity in response to LPS. Fragment 1279-1421 showed CREB and surprisingly YY1 oc-cupancy. Sequential ChIP experiments confirmed that YY1 and CREB interact in the 1279-1421 region. Our results suggest that CLDN6 expression is regulated by the binding of YY1 and CREB in the 901-1421 enhancer in which a non-described interaction of YY1 with CREB was established in the 1279-1421 region.

Background: CK-18 is a serological marker of apoptosis that has been widely associated with fibrosis and steatosis in NASH. Many studies have showed association CK-18 levels with NAFLD. To date, there is a profound lack of rheumatology studies on the effect of MTX therapy with regard to CK-18 levels. The relationship between CK-18 levels and cumulative MTX dose, MTX treatment duration, weekly MTX dose is not available in the literature. Objectives: The main purpose of this study was to determine the relationship between serum cytokeratin-18 (CK-18) and cumulative methotrexate dose in rheumatology patients on methotrexate (MTX) therapy. Besides, we studied the correlations between CK-18 and clinical parameters including age, disease duration , duration of MTX therapy, cumulative steroid dose and biochemical parameters such as alanine transaminase (ALT) and aspartate aminotransferase AST). Methods : We recruited 79 rheumatology patients on methotrexate (MTX) therapy as MTX group and 38 patients not on MTX therapy as non-MTX group . All subjects were tested for their serum CK-18 levels using an enzyme-linked immunosorbent assay (ELISA) test. We identified 20 patients with the highest CK-18 levels and 20 patients with the lowest CK-18 levels and had ultrasound liver performed on them. Results : The median serum CK-18 levels were marginally higher among the patients on MTX (1.20 ng/mL [0.19-37.15]) compared to the non-MTX group (1.17 ng/mL [0.37-34.32]). There was a significantly positive relationship between serum CK-18 levels and cumulative MTX dose (r = 0.329, p = 0.003) and total duration of MTX therapy (r = 0.284, p = 0.011). Apart from the above-mentioned variables, the CK-18 levels in MTX group significantly correlated with age (r = 0.265, p = 0.018), ALT (r = 0.440, p = <0.001) and AST (r = 0.478, p= 0.004). Ultrasound liver findings showed median CK-18 levels was higher among patients with abnormal liver findings although statistical significance was not reached. Conclusion : Among patients on MTX therapy, serum CK-18 levels correlated positively with cumulative MTX dose , total duration of MTX treatment , ALT and AST levels. These findings are preliminary and requires validation by future studies in the field of rheumatology.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months postoperatively. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. To our knowledge, this is the first report in English on mucin-positive signet-ring cells of CC arising in an intestinal-type IPMNHGD evaluated by SPACE cytology.

Claudins are a family of 27 proteins that have an important role in the formation of tight junc-tions. They also have an important function in ions exchange, cell mobility, and in in the epitheli-al-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evi-dence shows improved outcomes when combining monoclonal antibodies against Claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently Chimeric anti-gen receptor T-cells targeting Claudin 18 are under investigation.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions with diverse treatment options. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37 as potential therapeutic targets. This review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to May 30, 2024 underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still’s Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis.

Maize mosaic virus (MMV) is a plant virus that is transmitted by the corn planthopper, Peregrinus maidis Ashmead (Hemiptera: Delphacidae) in a persistent and propagative manner. MMV is the causal agent for mosaic disease that can cause significant loss in corn yield. Management is focused on controlling insect vector population. The molecular mechanisms of virus transmission by the insect vector are not fully understood. Previously, we identified a receptor for MMV, the P. maidis syntaxin 18 (PmStx18). PmStx18 interacts with the viral glycoprotein and potentially facilitates MMV recognition and entry into the vector, enabling virus proliferation. Stx18 is a key component of the vesicular trafficking machinery and also plays a critical role in neurotransmitter release in insects. In this work, we investigated the expression of PmStx18 in different developmental stages and major parts of the insect vector. Primers were designed to generate templates for synthesis of double-stranded RNA fragments. A 374-bp amplicon was selected and gene-specific sequences were flanked by T7 promoter sequences for in vitro transcription. Results showed a significant difference in the expression of Stx18 in the different developmental stages of P. maidis but not between male and female adults and major body parts. In vitro transcription products indicated optimal reaction conditions and protocol suitability. The findings establish the initial steps for developing RNAi-based approach in controlling MMV transmission by targeting Syntaxin-18 in P. maidis. Further investigations are needed to evaluate the efficacy of this approach.

High-power laser facilities necessitate predicting incremental damage to final optics to identify evolving damage trends. In this study, we propose a surface damage detection method utilizing image segmentation employing ResNet-18, and a damage area estimation network employing U-Net++. Paired sets of online and offline images of optics obtained from a large laser facility is used to train the network. The trends of varying damage could be identified by incorporating additional experimental parameters. A key advantage of the proposed method is that the network can be trained end-to-end on small samples, eliminating the need for manual labeling or feature extraction. The software developed based on these models can facilitate the daily inspection and maintenance of optics in large laser facilities.

The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. The properties of the Leak Pathway, such as its molecular mechanism, its regulation, and whether or not it has a size limit, remain controversial. This review will trace the evolution of the Leak Pathway concept from its origins, will discuss the current information about the properties of the Leak Pathway, and will discuss recent research suggesting a possible molecular basis for the Leak Pathway. Based on these findings, we propose a model for the molecular mechanism underlying the Leak Pathway and its regulation.

Microglia are the resident immune cells of the central nervous system. Upon stimulus presentation microglia polarize from a resting to an activated state. Microglial translocator protein 18 kDa (TSPO) is considered as a marker of inflammation. Here, we characterized the role of TSPO by investigating the impact of TSPO deficiency on human microglia. We used TSPO knockout (TSPO-/-) variants of the human C20 microglia cell line. We found a significant reduction in the TSPO-associated protein VDAC1 in TSPO-/- compared to control cells. Moreover, we assessed the impact of TSPO deficiency on calcium levels and the mitochondrial membrane potential. Cytosolic and mitochondrial calcium concentrations were increased in TSPO-/- cell lines, whereas the mitochondrial membrane potential tended to be lower. Assessment of the mitochondrial DNA copy number via RT-PCR revealed a decreased amount of mtDNA in the TSPO-/- cells when compared to controls. Moreover, metabolic profiles of C20 cells were strongly dependent on the glycolytic pathway. However, TSPO depletion did not affect the cellular metabolic profile. Measurement of the mRNA expression levels of the pro-inflammatory mediators revealed an attenuated response to proinflammatory stimuli in TSPO-depleted cells, implying a role of the TSPO protein in the process of microglial polarization.

In mammals, the role of interleukin-18 (IL-18) in the immune response is to drive inflammatory and, normally therefore, anti-viral responses. IL-18 also shows promise as a vaccine adjuvant in mammals. Chicken IL-18 (chIL-18) has been cloned. The aim of this study was to investigate the potential of chIL-18 to act as a vaccine adjuvant in the context of a live recombinant Fowlpox virus vaccine (fpIBD1) against Infectious bursal disease virus (IBDV). fpIBD1 protects against mortality, but not against damage to the bursa of Fabricius caused by IBDV infection. The Fowlpox virus genome itself contains several candidate immunomodulatory genes, including potential IL-18 binding proteins (IL-18bp). We have knocked out (Δ) the potential IL-18bp genes in fpIBD1 and inserted (::) the cDNA encoding chIL-18 into fpIBD1 in the non-essential ORF030, generating five new viral constructs –fpIBD1::chIL-18, fpIBD1ΔORF073, fpIBD1ΔORF073::chIL-18, fpIBD1ΔORF214 and fpIBD1ΔORF214::chIL-18. The subsequent protection from challenge with virulent IBDV, as measured by viral load and bursal damage, given by these altered fpIBD1 strains, was compared to that given by the original fpIBD1. The results show that chIL-18 can act as a vaccine adjuvant, giving complete protection against challenge, with no detectable virus or damage in the bursa of Fabricius.

In the field of 18F-chemistry for the development of radiopharmaceuticals for positron emission tomography (PET), various labeling strategies by the use of prosthetic groups have been im-plemented, including chemoselective 18F-labeling of biomolecules. Among those, chemoselec-tive 18F-fluoroglycosylation methods focus on the sweetening of pharmaceutical radiochemistry by offering a highly valuable tool for the synthesis of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. A previous review covered the various 18F-fluoroglycosylation methods that have been developed and applied as of 2014 [Maschauer and Prante, BioMed. Res. Int. 2014, 214748]. This paper is an updated review, providing the recent progress in 18F-fluoroglycosylation reactions and the preclinical application of 18F-glycoconjugates, including small molecules, peptides, and high-molecular-weight proteins.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

Radiolabelled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection we recently developed the fluorine-18 labelled PSMA-ligand [¹⁸F]PSMA-1007 as next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far was suffering for rather poor yields novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly used radiosynthesisers. Using the novel one-step procedure the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 30-70 % and synthesis times less than 55 minutes. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and at the same time high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and thus transferable onto all currently available radiosynthesisers. Using the new procedures, clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

Cytokines play a substantial role in the pathophysiology of infectious diseases. Consequently, genetic polymorphisms in cytokine genes can have profound effect on the susceptibility to or protection from infections and also influence the clinical manifestations, disease severity as well as outcome. The objective of this brief narrative review is to provide an update on the recent research findings on the role of genetic polymorphisms of IL-18, a recently discovered cytokine on certain infectious diseases of public health relevance. The current review suggests there is a significant impact of IL-18 polymorphisms on different infectious diseases. The presence of G and T alleles at position -656 is suggested to have a probable protective effect against VL. The −137G/−607C (GC) and −137C/−607C (CC) haplotypes in the promoter region are associated with increased susceptibility to severe malarial anemia. SNPs rs544354 and rs574429 (GC) are linked to a higher risk of P. falciparum infection and increased parasitemia. The -137 C/C genotype and -137 G allele (with G/G genotype) are associated with faster progression to AIDS. In contrast, the IL-18 genotype does not seem to affect overall HIV susceptibility but influences disease progression. The G and GG genotypes at position -137 and allele A at position -607 are likely associated with protection against HBV infection. Conversely, the C allele at position -137 is linked to increased susceptibility to HBV infections. The GG genotype of IL-18 -137 G > C variant is associated with increased susceptibility to pulmonary tuberculosis (PTB). The AC genotype of IL-18 -607A>C has been linked to PTB susceptibility, particularly in patients with co-morbid diabetes mellitus. SNPs −137G/C, 113T/G, and +127C/T are associated with susceptibility to H. pylori infection, indicating that these genetic variants may influence the risk of H. pylori-related diseases. There are conflicting results in studies conducted in different populations (e.g., genetic polymorphism, studies conducted in India and China against HBV infection) highlighting the need for further research with larger sample sizes to resolve discrepancies. Due to the variability in findings, extensive studies in diverse populations are needed to better understand the impact of IL-18 polymorphisms.

Background: Cytokines are multifunctional glycoproteins playing a vital role in the tumor microenvironment and in the progression of breast cancer. The immune responses in the tumors restrained by pro- and anti-inflammatory cytokine expressions could be influenced by genetic polymorphisms. Hence, the present study evaluated the contribution of IL6 (rs1800797, rs1800796, and rs1800795), and IL18 (rs1946518, rs187238, and rs549908) genotypes and its haplotypes with risk and progression of breast cancer in south Indian population. Methods: The polymorphisms of IL6 gene -597G>A, -572G>C, -174G>C and IL18 gene -607C>A, -137G>C, and 105A>T were genotyped through PCR-RFLP and As-PCR assays in blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression and Kaplan-Meier analyses for the obtained data. Results: The frequency of AA genotype & A-allele of IL6 -597G>A, and CC genotype & C allele of IL6 -174G>C polymorphism was higher in breast cancer patients and was found to be significantly associated with TNM staging, late (advanced) stage, metastasis, etc. While, CG and GG genotypes of IL6 -572 C>G polymorphism had a protective role against breast cancer. Further, IL18 -607C>A, -137G>C & 105A>T polymorphisms were found to be associated with lobular carcinoma subtype, PR-ve and HER2+ve breast cancer patients. Perfect LD was observed between all SNPs of IL6 & IL18 genes under study; G-C-C, A-G-G and A-C-C haplotype combination of IL6 genes had conferred 2.09, 2.25 and 4.72 folds risk for breast cancer respectively. In survival analysis, we observed that the C allele of rs 1800795 was found to be significantly associated with 5years overall survival in breast cancer subjects. Conclusions: Overall, our results suggest the importance of genotypic and haplotype analysis of IL6, and IL18 gene variants in progression and risk identification of breast cancer.

Stable isotope concentrations in the soil, rain and ground water have been used to trace the water extraction zones of plants in different environments. The need to identify the plant water use by plants in afforestation programs to control desertification increases the importance of sap water partitioning of plants in sand dune areas. However, the introduction of new plant covers exerts pressure on the water resources and can affect the local soil water conditions. In this study, we analyzed the isotope concentrations in rain, soil, sap, and ground water after the summer of 2010. Two experimental plots established in the Hailiutu catchment (Shaanxi province, northwest China) were selected to gather the water samples between September and October 2010. One plot is dominated by Salix bushes (Salix psammophila C. Wang \& Chang Y. Yang) and the other by the tree species Willow (Salix matsudana Koidz.). The total precipitation at the experimental site was 401 mm/yr during 2010, while 88.7 mm was collected in total for the period September to October. Willow trees transpired 12.82 kg/d being almost three times larger than Salix shrubs (4.57 kg/d). Despite the transpiration rates of both plant species and the few rain events in the region, the soil water beneath the plant covers is not depleted. Stable isotope signature of soil water beneath both covers shows the fractionation front in Salix at 20 cm depth and at Willow at 40 cm depth. However, soil water signature is closer to the groundwater than the collected rain water.

Single crystal nickel-based superalloys are extensively used in turbine blade applications 1 due to their superior creep resistance compared to their polycrystalline counterparts. With the high 2 creep resistance, High Cycle Fatigue (HCF) and Low Cycle Fatigue (Single crystal nickel-based 3 superalloys are extensively used in turbine blade applications due to their superior creep resistance 4 compared to polycrystalline counterparts. As a result, fatigue becomes the primary failure mechanism 5 in such applications. Specifically, High Cycle Fatigue (HCF) and Low Cycle Fatigue (LCF) are of 6 significant concern under these conditions. This study investigates the fatigue life prediction of 7 CMSX-4 using a combined crystal plasticity and lifetime assessment model. The constitutive crystal 8 plasticity model simulates the anisotropic, rate-dependent deformation behavior of CMSX-4, while 9 a modified Chaboche damage model is used for lifetime assessment, incorporating anisotropy by 10 focusing on cleavage stresses on active slip planes. Both qualitative and quantitative data obtained 11 from HCF experiments on single crystal superalloys with notched geometry were used to validate 12 the model. Furthermore, artificial neural networks (ANNs) were employed to enhance the accuracy 13 of lifetime predictions across varying temperatures by analyzing the stress-strain data obtained from 14 simulations. The integration of crystal plasticity, damage mechanics, and ANNs resulted in accurate 15 predictions of fatigue life and crack initiation points under complex loading conditions of single 16 crystal superalloys.

Drinking water contamination of lead from various environmental sources, leaching consumer products and intrinsic water-pipe infrastructure is still today a matter of great concern. Therefore, new highly sensitive and convenient Pb²⁺ measurement schemes are necessary, especially for in-situ measurements at a low-cost. Within this work dye/ionophore/Pb²⁺ co-extraction and effective water phase de-colorization was utilized for highly sensitive lead measurements and sub-ppb naked-eye detection. A low-cost ionophore Benzo-18-Crown-6-ether was used, and a simple test-tube mix and separate procedure was developed. Instrumental detection limits were in the low ppt region (LOD=3, LOQ=10), and naked-eye detection was 500 ppt. Note, however, that this sensing scheme still has improvement potential as concentrations of fluorophore and ionophore were not optimized. Artificial tap-water samples, leached by a standardized method, demonstrated drinking water application. Implications for this method are convenient in-situ lead ion measurements.

Early stable deep molecular response (DMR) of nilotinib is associated with goal of treatment-free remission (TFR) for patients with chronic-phase chronic myeloid leukemia (CML-CP). It is significant to early distinguish patients who can obtain DMR and fit for TFR. We performed a multicenter study to explore early cumulative MR4.5 rate by 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. From 29 institutes, 106 ND-CML-CP patients received nilotinib (300mg BID). The cumulative MR4.5 rate of nilotinib by 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates of nilotinib by 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with ultra-early molecular response (u-EMR) at 6 weeks were not significantly different to obtain DMR or MMR by 24 months compared to those without u-EMR (P=0.7584, P=0.9543, respectively). Our study demonstrated that treatment with nilotinib in patients with ND-CML-CP contributed to obtain high early MR4.5.

Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have a different impact on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (IHC) to evaluate five markers (Mesothelin, Claudin-15, Complement Factor B, Plasminogen Activator Inhibitor 1, and p21-activated Kinase 4), whose encoding genes have been previously reported as deregulated among PM subtypes. Immunohistochemical expressions were determined in a case series of 73 PMs, and cut-offs for the epithelioid and non-epithelioid subtypes were selected. Further validation was performed on an independent cohort (30 PMs). For biphasic PM, the percentage of the epithelioid component was assessed, and IHC evaluation was also performed on the individual components separately. Mesothelin and Claudin-15 showed a good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had an inferior performance, with higher sensitivity (89% and 84%), but lower specificity (64% and 36%). In the biphasic group, all markers showed a different expression when comparing epithelioid with sarcomatoid areas. Mesothelin, Claudin-15 and CFB can be useful in subtype discrimination. PAI1 and PAK4 can improve component distinction in biphasic PM.

In the era of the post-quantum Internet of Things (IoT), the implementation of anti-quantum cryptographic algorithms in numerous terminals can successfully defend against prospective quantum computing assaults. Lattice-based cryptography can withstand quantum computing attacks, making it a viable substitute for the currently prevalent classical public-key cryptographic technique. Nevertheless, the algorithm’s significant time complexity will result in a substantial computational burden on the edge computing chip in the IoT terminal. The computation of polynomial multiplication is the most demanding task in lattice-based cryptographic algorithms. Therefore, the investigation into efficient methods for calculating polynomial multiplication is highly important. Quick number theory transformations (NTT) are a widely employed technique to accelerate polynomial multiplication. This study presents a hardware implementation of an efficient number theory transformation. We utilize a multi-level pipeline architecture in the design to accomplish parallel calculations and execute it on a low-profile Artix7-XC7A100T FPGA device. The performance evaluation results demonstrate that our implementation significantly enhances performance and reduces resource usage compared to other existing proposals on the same platform. We suggested NTT core can be implemented in edge computing chips to enhance computational speed due to its small and low-latency design. The experimental results show that the proposed design, which supports both NTT and inverse NTT, achieves 417-Megahertz and consumes only 541-LUTs on Artix-7 XC7A100T.

PET imaging with [¹⁸F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [¹⁸F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [¹⁸F]F-DOPA uptake. 73 subjects with treatment-naïve low and high-grade gliomas, who underwent brain MRI within two weeks of [¹⁸vF]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357), though significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Our framework aids in analyzing [¹⁸F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

The AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN (AHL) gene family encodes embryophyte-specific nuclear proteins with DNA binding activity. They modulate gene expression and affect various developmental processes in plants. We identify AHL18 (At3G60870) as a developmental modulator of root system architecture and growth. AHL18 regulates the length of the proliferation domain and number of dividing cells in the root apical meristem and thereby, cell production. Both primary root growth and lateral root development respond according to AHL18 transcription level. The ahl18 knock-out plants show reduced root systems due to a shorter primary root and a lower number of lateral roots. This change results from a higher number of arrested and non-developing lateral root primordia (LRP) rather than from decreased initiation. Overexpression of AHL18 results in a more extensive root system, longer primary roots, and increased density of lateral root initiation events. Formation of lateral roots is affected during the initiation of LRP and later development. AHL18 regulate root apical meristem activity, lateral root initiation and emergence, which is in accord with localization of its expression.

Borderline ovarian tumors (BOTs) show intriguing characteristics distinguishing them from other ovarian tumors. This unique type of non-invasive neoplasms is characterized by atypical growth of epithelial cells, nuclear atypia, and a moderate-level mitotic activity that places BOTs between benign tumors and invasive cancers. Similar to invasive carcinomas, BOTs can be categorized into six histological subtypes based on the type of epithelial cells present. The most prevalent subtypes are serous and mucinous BOTs, whereas endometrioid, clear cell, seromucinous, and borderline Brenner tumors are diagnosed less often. Noticeably, molecular changes found in BOTs can vary on a case-by-case basis, which warrants further research on the molecular landscape of these tumors. Identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. A growing body of evidence indicates that BOTs often remain clinically dormant for extended periods before a molecular trigger initiates increased cell replication, potentially leading to carcinoma development or recurrence. Continued research in this area is crucial for improving risk assessment and developing personalized treatment approaches. While molecular studies have contributed significantly to our understanding of BOT pathogenesis, substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches. The aim of the present systematic review was to analyze the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach.

Hate Speech Detection in Arabic presents a multifaceted challenge due to the broad and diverse linguistic terrain. With its multiple dialects and rich cultural subtleties, Arabic requires particular measures to address hate speech online successfully. To address this issue, academics and developers have used natural language processing (NLP) methods and machine learning algorithms adapted to the complexities of Arabic text. However, many proposed methods were hampered by a lack of a comprehensive dataset/corpus of Arabic hate speech. In this research, we propose a novel multi-class public Arabic dataset comprised of 403,688 annotated tweets categorized as extremely positive, positive, neutral, or negative based on the presence of hate speech. Using our developed dataset, we additionally characterize the performance of multiple machine learning models for Hate speech identification in Arabic Jordanian dialect tweets. Specifically, the Word2Vec, TF-IDF, and AraBert text representation models have been applied to produce word vectors. With the help of these models, we can provide classification models with vectors representing text. After that, seven Machine learning classifiers have been evaluated: Support Vector Machine (SVM), Logistic Regression (LR), Naive Bays (NB), Random Forest (RF), AdaBoost (Ada), XGBoost (XGB), and CatBoost (CatB). In light of this, the experimental evaluation revealed that, in this challenging and unstructured setting, our gathered and annotated datasets were rather efficient and generated encouraging assessment outcomes. This will enable academics to delve further into this crucial field of study.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

Fecal contamination is a common cause of impairment of surface waters. In monitoring studies, it usually is assessed by measuring concentrations of fecal indicator bacteria such as Escherichia coli (E. coli), a common monitoring target in freshwater systems. In this study, we assess the advantages and disadvantages of two common methods for monitoring E. coli concentrations at freshwater beaches: Colilert-18®, with a turnaround time of ca. 18 h, and real-time quantitative PCR (qPCR), with a turnaround time of ca. 3–4 h. Based on data comprising 3081 pairs of Colilert-18 and qPCR estimates of E. coli concentrations in split samples from Michigan’s annual beach monitoring program in 2019 and 2020, we found that qPCR monitoring detected a high percentage of exceedances of the state’s water quality standard for E. coli contamination that went undetected on the day of sampling with Colilert-18 monitoring, because qPCR concentration estimates were available on the day of sampling but Colilert-18 estimates were not. However, Colilert-18 data were more useful than qPCR data for statistical comparison of contamination levels at different beaches, probably in part because Colilert-18 data showed a much lower percentage of censored concentration estimates (estimates outside the range of quantification).

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

Mild traumatic brain injury mTBI is a common occurrence around the world, associated with a variety of blunt force and torsion injuries affecting all age groups. Most never reach medical attention, and identification of acute injury and later clearance to return to usual activities is relegated to clinical evaluation particularly in sports injuries. Advanced structural imaging is rarely performed due to the usual absence of associated acute anatomic/hemorrhagic changes. This review targets physiologic imaging techniques available to identify subtle blood brain barrier dysfunction and white matter tract shear injury, and their association with chronic traumatic encephalopathy. These techniques provide needed objective measures to assure recovery from injury in those patients with persistent cognitive/emotional symptoms and in the face of repetitive mTBI.

A contribution of Epstein-Barr Virus (EBV), Human Cytomegalovirus (HCMV), and certain types of Human Papilloma Virus (HPV) to the overall pathogenesis of upper airways cancers seems a priori reasonably conceivable. The existing evidence mostly relates them to nasopharyngeal squamous and undifferentiated carcinomas; indications emerge about their involvement in other upper airways cancers too. Markers of EBV, HCMV, HPV16, HPV18, (and Mycoplasma pneumoniae as a negative control) were searched in a series of 68 samples of neoplastic tissues from 57 patients diagnosed with different upper airways cancers. The results provide clues in favor of an actual role of EBV, HCMV, and HPV18, in the web of causation of upper airways squamous and undifferentiated carcinomas, possibly of upper airways adenocarcinomas too.