Search

Abstract The study aimed to evaluate the impact of AI assistance on pulmonary nodule detection rates among radiology residents and senior radiologists, along with assessing the effectiveness of two different commercialy available AI software systems in improving detection rates and LungRADS classification in chest CT. The study cohort included 198 participants with 221 pulmonary nodules. Residents’ mean detection rate increased significantly from 64 to 77% with AI assist, while seniors’ detection rate remained largely unchanged (85% vs. 86%). Residents showed significant improvement in segmental nodule localization with AI assistance, seniors did not. Software 2 slightly outperformed software 1 in increasing detection rates (67–77% vs. 80–86%), but neither significantly affected LungRADS classification. The study suggests that clinical experience mitigates the need for additional AI software, with the combination of CAD with residents being the most beneficial approach. Both software systems performed similarly, with software 2 showing a slightly higher but non-significant increase in detection rates.

Twelve Communist trade union leaders from nine nations in the prosperous post-war period are compared, on the basis of an in-depth Belgian example, in an attempt to define their common theoretical profile. Five major analogies, from family origins to the end of their careers, offer a hypothetical look at the militant career of twelve workers with little schooling who fought major socio-political conflicts with their factory workers and took on major responsibilities at the head of their union and party, not without encountering numerous problems and internal tensions. This analysis provides a glimpse into the ethos of a particular type of trade unionist and the environment that led them to surpass themselves and break through the glass ceiling of social reproduction, without betraying the aspirations and values of their class.

To determine the diagnostic performance of simulated reduced-dose chest CT scans regarding pulmonary T1 tumors and assess the potential impact on patient management, a repository of 218 patients with histologically proven pulmonary T1 tumors was used. Virtual reduced-dose images were simulated at 25%- and 5%-dose levels. Tumor size, attenuation, and localization were scored by two experienced chest radiologists. The impact on patient management was assessed by comparing hypothetical LungRADS scores. The study included 210 patients (41% females, mean age 64.5 ± 9.2 years) with 250 eligible T1 tumors. There were differences between the original and the 5%—but not the 25%—dose simulations, and LungRADS scores varied between the dose levels with no clear trend. Sensitivity of Reader 1 was significantly lower using the 5%-dose vs. 25%-dose vs. original dose for size categorization (0.80 vs. 0.85 vs. 0.84; p = 0.007) and segmental localization (0.81 vs. 0.86 vs. 0.83; p = 0.018). Sensitivities of Reader 2 were unaffected by a dose reduction. A CT dose reduction may affect the correct categorization and localization of pulmonary T1 tumors and potentially affect patient management.

Abstract We evaluated the effectiveness of automated segmentation of the liver and its vessels with a convolutional neural network on non-contrast T1 vibe Dixon acquisitions. A dataset of non-contrast T1 vibe Dixon liver magnetic resonance images was labelled slice-by-slice for the outer liver border, portal, and hepatic veins by an expert. A 3D U-Net convolutional neural network was trained with different combinations of Dixon in-phase, opposed-phase, water, and fat reconstructions. The neural network trained with the single-modal in-phase reconstructions achieved a high performance for liver parenchyma (Dice 0.936 ± 0.02), portal veins (0.634 ± 0.09), and hepatic veins (0.532 ± 0.12) segmentation. No benefit of using multi-modal input was observed (p = 1.0 for all experiments), combining in-phase, opposed-phase, fat, and water reconstruction. Accuracy for differentiation between portal and hepatic veins was 99% for portal veins and 97% for hepatic veins in the central region and slightly lower in the peripheral region (91% for portal veins, 80% for hepatic veins). In conclusion, deep learning-based automated segmentation of the liver and its vessels on non-contrast T1 vibe Dixon was highly effective. The single-modal in-phase input achieved the best performance in segmentation and differentiation between portal and hepatic veins.

Abstract Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child–Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126–0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p

Langerhans cell histiocytosis (LCH) is a myeloid neoplasm with inflammatory properties. There are few published reports of adult LCH with liver involvement, which is still poorly understood, but shows high morbidity and mortality. We report a case of a 37-year-old woman suffering from hepatitis C showing a LCH affecting the lung as well as the liver. Consistent with histology, we found an early stage of a proliferative/granulomatous phase of hepatobiliary LCH, whereas pulmonary findings showed a nodular stage of adult pulmonary LCH. Although hepatocellular carcinoma is a common malignancy in patients suffering from hepatitis C, it is crucial to keep in mind differential diagnosis for newly appearing liver lesions.

Natural gas hydrates are increasingly viewed as a potential economic resource as energy demands rise. In this study, three-dimensional seismic data for Block 26 in the Atlantic Continental Margin offshore Trinidad were evaluated to determine if there is the potential for oceanic hydrate-bearing sediments. The seismic dataset covered an area of approximately 1210 km2 of the continental slope. A bottom simulating reflector which generally ran parallel to the sea floor and cut the dominant stratigraphy was observed and mapped over approximately 43% of the study area.

Inflammatory bowel disease, comprising Crohn's disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD.

Inflammation of the GI tract leads to compromised epithelial barrier integrity, which increases intestine permeability. A compromised intestinal barrier is a critical event that leads to microbe entry and promotes inflammatory responses. Inflammatory bowel diseases that comprise Crohn's disease (CD) and ulcerative colitis (UC) show an increase in intestinal permeability. Nerolidol (NED), a naturally occurring sesquiterpene alcohol, has potent anti-inflammatory properties in preclinical models of colon inflammation. In this study, we investigated the effect of NED on MAPKs, NF-κB signaling pathways, and intestine epithelial tight junction physiology using in vivo and in vitro models. The effect of NED on proinflammatory cytokine release and MAPK and NF-κB signaling pathways were evaluated using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. Subsequently, the role of NED on MAPKs, NF-κB signaling, and the intestine tight junction integrity were assessed using DSS-induced colitis and LPS-stimulated Caco-2 cell culture models. Our result indicates that NED pre-treatment significantly inhibited proinflammatory cytokine release, expression of proteins involved in MAP kinase, and NF-κB signaling pathways in LPS-stimulated RAW macrophages and DSS-induced colitis. Furthermore, NED treatment significantly decreased FITC-dextran permeability in DSS-induced colitis. NED treatment enhanced tight junction protein expression (claudin-1, 3, 7, and occludin). Time-dependent increases in transepithelial electrical resistance (TEER) measurements reflect the formation of healthy tight junctions in the Caco-2 monolayer. LPS-stimulated Caco-2 showed a significant decrease in TEER. However, NED pre-treatment significantly prevented the fall in TEER measurements, indicating its protective role. In conclusion, NED significantly decreased MAPK and NF-κB signaling pathways and decreased tight junction permeability by enhancing epithelial tight junction protein expression.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

Abstract Background Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-β2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-β in retinoic acid-mediated growth inhibition in pancreatic cancer cells. Results Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-β2 mRNA content and secretion of the active and latent forms of TGF-β2 (measured by ELISA and bioassay). The concentrations of active and TGF-β2 secreted in response to 0.1 – 10 μM retinoic acid were between 1–5 pM. TGF-β2 concentrations within this range also inhibited proliferation. A TGF-β neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells. Conclusion These findings indicate that TGF-β can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-β in growth inhibition in response to retinoic acid treatment is preserved in vitro.

Abstract Background Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. Results Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. Conclusion Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer.

Abstract Background Cyclooxygenase 2 (COX-2), the inducible form of prostaglandin G/H synthase, is associated with several human cancers including pancreatic adenocarcinoma. Pancreatic stellate cells (PSCs) play a central role in the intense desmoplasia that surrounds pancreatic adenocarcinoma. The present study examined COX-2 expression in PSCs. PSCs isolated from normal rats, were cultured and exposed to conditioned medium (CM) from the human pancreatic cell line, PANC-1. Methods COX-2 expression was evaluated by immunostaining and western blotting. Proliferation of PSCs was determined by thymidine incorporation and cell counting. Results COX-2 was found to be constitutively expressed in PSCs, and COX-2 protein was up-regulated by PANC-1 CM. Moreover, the induction of COX-2 by PANC-1 CM was prevented by U0126, an extracellular signal-regulated kinase (ERK) 1/2 inhibitor suggesting that activation of ERK 1/2 is needed for stimulation of COX-2. Finally, NS398, a selective COX-2 inhibitor, reduced the growth of PSCs by PANC-1 CM, indicating that activation of COX-2 is required for cancer stimulated PSC proliferation. Conclusion The results suggest that COX-2 may play an important role in the regulation of PSC proliferation in response to pancreatic cancer.

Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1) our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2) the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.

Background: Extracellular volume (ECV) correlates with the degree of liver fibrosis. Purpose: To analyze the performance of liver MRI‐based ECV evaluations with different blood pool measurements at different time points. Study Type: Prospective. Sample: 73 consecutive patients (n = 31 females, mean age 56 years) with histopathology‐proven liver fibrosis. Field Strength/Sequence: 3T acquisition within 90 days of biopsy, including shortened modified look–locker inversion recovery T1 mapping. Assessment: Polygonal regions of interest were manually drawn in the liver, aorta, vena cava, and in the main, left and right portal vein on four slices before and after Gd‐DOTA administration at 5/10/15 minutes. ECV was calculated 1) on one single slice on portal bifurcation level, and 2) averaged over all four slices. Statistical Tests: Parameters were compared between patients with fibrosis grades F0‐2 and F3‐F4 with the Mann–Whitney U and fishers exact test. ROC analysis was used to assess the performance of the parameters to predict F3‐4 fibrosis. A P‐value <0.05 was considered statistically significant. Results: ECV was significantly higher in F3‐4 fibrosis (35.4% [33.1%–37.6%], 36.1% [34.2%–37.5%], and 37.0% [34.8%–39.2%] at 5/10/15 minutes) than in patients with F0‐2 fibrosis (33.3% [30.8%–34.8%], 33.7% [31.6%–34.7%] and 34.9% [32.2%–36.0%]; AUC = 0.72–0.75). Blood pool T1 relaxation times in the aorta and vena cava were longer on the upper vs. lower slices at 5 minutes, but not at 10/15 minutes. AUC values were similar when measured on a single slice (AUC = 0.69–0.72) or based on blood pool measurements in the cava or portal vein (AUC = 0.63–0.67 and AUC = 0.65–0.70). Data Conclusion: Liver ECV is significantly higher in F3‐4 fibrosis compared to F0‐2 fibrosis with blood pool measurements performed in the aorta, inferior vena cava, and portal vein at 5, 10, and 15 minutes. However, a smaller variability was observed for blood pool measurements between slices at 15 minutes. Level of Evidence: 1 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

To determine the diagnostic performance of simulated reduced-dose chest CT scans regarding pulmonary T1 tumors and assess the potential impact on patient management, a repository of 218 patients with histologically proven pulmonary T1 tumors was used. Virtual reduced-dose images were simulated at 25%- and 5%-dose levels. Tumor size, attenuation, and localization were scored by two experienced chest radiologists. The impact on patient management was assessed by comparing hypothetical LungRADS scores. The study included 210 patients (41% females, mean age 64.5 ± 9.2 years) with 250 eligible T1 tumors. There were differences between the original and the 5%—but not the 25%—dose simulations, and LungRADS scores varied between the dose levels with no clear trend. Sensitivity of Reader 1 was significantly lower using the 5%-dose vs. 25%-dose vs. original dose for size categorization (0.80 vs. 0.85 vs. 0.84; p = 0.007) and segmental localization (0.81 vs. 0.86 vs. 0.83; p = 0.018). Sensitivities of Reader 2 were unaffected by a dose reduction. A CT dose reduction may affect the correct categorization and localization of pulmonary T1 tumors and potentially affect patient management. [ABSTRACT FROM AUTHOR]

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is rising globally. However, the etiology of IBD is complex and governed by multiple factors. The current clinical treatment for IBD mainly includes steroids, biological agents and need-based surgery, based on the severity of the disease. Current drug therapy is often associated with adverse effects, which limits its use. Therefore, it necessitates the search for new drug candidates. In this pursuit, phytochemicals take the lead in the search for drug candidates to benefit from IBD treatment. β-myrcene is a natural phytochemical compound present in various plant species which possesses potent anti-inflammatory activity. Here we investigated the role of β-myrcene on colon inflammation to explore its molecular targets. We used 2% DSS colitis and TNF-α challenged HT-29 adenocarcinoma cells as in vivo and in vitro models. Our result indicated that the administration of β-myrcene in dextran sodium sulfate (DSS)-treated mice restored colon length, decreased disease activity index (DAI), myeloperoxidase (MPO) enzyme activity and suppressed proinflammatory mediators. β-myrcene administration suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways to limit inflammation. β-myrcene also suppressed mRNA expression of proinflammatory chemokines in tumor necrosis factor-α (TNF-α) challenged HT-29 adenocarcinoma cells. In conclusion, β-myrcene administration suppresses colon inflammation by inhibiting MAP kinases and NF-κB pathways. [ABSTRACT FROM AUTHOR]

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010–2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of inflammatory bowel disease (IBD, Crohn's disease, and ulcerative colitis) are increasing worldwide. The etiology of IBD is multifactorial, including genetic predisposition, dysregulated immune response, microbial dysbiosis, and environmental factors. However, many of the existing therapies are associated with marked side effects. Therefore, the development of new drugs for IBD treatment is an important area of investigation. Here, we investigated the anti-inflammatory effects of α-bisabolol, a naturally occurring monocyclic sesquiterpene alcohol present in many aromatic plants, in colonic inflammation. To address this, we used molecular docking and dynamic studies to understand how α-bisabolol interacts with PPAR-γ, which is highly expressed in the colonic epithelium: in vivo (mice) and in vitro (RAW264.7 macrophages and HT-29 colonic adenocarcinoma cells) models. The molecular docking and dynamic analysis revealed that α-bisabolol interacts with PPAR-γ, a nuclear receptor protein that is highly expressed in the colon epithelium. Treatment with α-bisabolol in DSS-administered mice significantly reduced Disease Activity Index (DAI), myeloperoxidase (MPO) activity, and colonic length and protected the microarchitecture of the colon. α-Bisabolol treatment also reduced the expression of proinflammatory cytokines (IL-6, IL1β, TNF-α, and IL-17A) at the protein and mRNA levels. The expression of COX-2 and iNOS inflammatory mediators were reduced along with tissue nitrite levels. Furthermore, α-bisabolol decreased the phosphorylation of activated mitogen-activated protein kinase (MAPK) signaling and nuclear factor kappa B (NFκB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. However, the PPAR-α and β/δ expression was not altered, indicating α-bisabolol is a specific stimulator of PPAR-γ. α-Bisabolol also increased the PPAR-γ transcription factor expression but not PPAR-α and β/δ in pretreated in LPS-stimulated RAW264.7 macrophages. α-Bisabolol significantly decreased the expression of proinflammatory chemokines (CXCL-1 and IL-8) mRNA in HT-29 cells treated with TNF-α and HT-29 PPAR-γ promoter activity. These results demonstrate that α-bisabolol mitigates colonic inflammation by inhibiting MAPK signaling and stimulating PPAR-γ expression. [ABSTRACT FROM AUTHOR]