Search Results (112,790)

The accurate segmentation of skin lesions plays an important role in the diagnosis and treatment of skin cancers. However, skin lesion areas are rich in details and local features, including the appearance, size, shape, texture, etc., which pose challenges for the accurate localization and segmentation of the target area. Unfortunately, the consecutive pooling and stride convolutional operations in existing convolutional neural network (CNN)-based solutions lead to the loss of some spatial information and thus constrain the accuracy of lesion region segmentation. In addition, using only the traditional loss function in CNN cannot ensure that the model is adequately trained. In this study, a generative adversarial network is proposed, with global and local semantic feature awareness (GLSFA-GAN) for skin lesion segmentation based on adversarial training. Specifically, in the generator, a multi-scale localized feature fusion module and an effective channel-attention module are designed to acquire the multi-scale local detailed information of the skin lesion area. In addition, a global context extraction module in the bottleneck between the encoder and decoder of the generator is used to capture more global semantic features and spatial information about the lesion. After that, we use an adversarial training strategy to make the discriminator discern the generated labels and the segmentation prediction maps, which assists the generator in yielding more accurate segmentation maps. Our proposed model was trained and validated on three public skin lesion challenge datasets involving the ISIC2017, ISIC2018, and HAM10000, and the experimental results confirm that our proposed method provides a superior segmentation performance and outperforms several comparative methods. Full article

Large language models (LLMs) are transforming the medical landscape by enhancing access to information, diagnostics, treatment customization, and medical education, especially in areas like Gastroenterology. LLMs utilize extensive medical data to improve decision-making, leading to better patient outcomes and personalized medicine. These models are instrumental in interpreting medical literature and synthesizing patient data, facilitating real-time knowledge for physicians and supporting educational pursuits in medicine. Despite their potential, the complete integration of LLMs in real-life remains ongoing, particularly requiring further study and regulation. This review highlights the existing evidence supporting LLMs’ use in Gastroenterology, addressing both their potential and limitations. Recent studies demonstrate LLMs’ ability to answer questions from physicians and patients accurately. Specific applications in this field, such as colonoscopy, screening for colorectal cancer, and hepatobiliary and inflammatory bowel diseases, underscore LLMs’ promise in improving the communication and understanding of complex medical scenarios. Moreover, the review discusses LLMs’ efficacy in clinical contexts, providing guideline-based recommendations and supporting decision-making processes. Despite these advancements, challenges such as data completeness, reference suitability, variability in response accuracy, dependency on input phrasing, and a lack of patient-generated questions underscore limitations in reproducibility and generalizability. The effective integration of LLMs into medical practice demands refinement tailored to specific medical contexts and guidelines. Overall, while LLMs hold significant potential in transforming medical practice, ongoing development and contextual training are essential to fully realize their benefits. Full article

Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease. Full article

Esophageal carcinoma is an aggressive cancer with a poor therapeutic response and a significant risk of recurrence after radical resection. It usually metastasizes to the lung, bones, or liver. Unusual spread can be found in other organs, but only nine cases of pancreatic metastases have been reported in the Medline database. In the present paper, a literature review of nine cases with esophageal squamous cell carcinoma and pancreatic metastasis was carried out. In addition to these cases, we present our case, the tenth case in the literature. It involved a patient who underwent surgery for esophageal squamous cell carcinoma and developed metachronous pancreatic metastasis 67 months after esophagectomy. Histopathological examination confirmed a squamous cell carcinoma metastasis. Conclusions: Pancreatic metastasis of esophageal squamous cell carcinoma is extremely rare. Pancreatic metastasis may develop several years after the treatment of the primary lesion. The diagnosis of metastasis is difficult, requiring histopathological and immunohistochemical examination. Full article

To fill a research gap on firefighter exposures and breast cancer risk, and guide exposure reduction, we aimed to identify firefighter occupational exposures linked to breast cancer. We conducted a systematic search and review to identify firefighter chemical exposures and then identified the subset that was associated with breast cancer. To do this, we compared the firefighter exposures with chemicals that have been shown to increase breast cancer risk in epidemiological studies or increase mammary gland tumors in experimental toxicology studies. For each exposure, we assigned a strength of evidence for the association with firefighter occupation and for the association with breast cancer risk. We identified twelve chemicals or chemical groups that were both linked to breast cancer and were firefighter occupational exposures, including polycyclic aromatic hydrocarbons, volatile aromatics, per- and polyfluoroalkyl substances, persistent organohalogens, and halogenated organophosphate flame retardants. Many of these were found at elevated levels in firefighting environments and were statistically significantly higher in firefighters after firefighting or when compared to the general population. Common exposure sources included combustion byproducts, diesel fuel and exhaust, firefighting foams, and flame retardants. Our findings highlight breast-cancer-related chemical exposures in the firefighting profession to guide equitable worker’s compensation policies and exposure reduction. Full article

Background/Objectives: Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms. Methods: A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF–GSE complex extract at ratios of 1:1, 1:2, and 2:1. Results: Treatment with the SJF–GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48–72 mg/g sophoricoside and 8–12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles. Conclusions: The SJF–GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause. Full article

Background: Gliomas, the most prevalent type of primary brain tumor, stand out as one of the most aggressive and lethal types of human cancer. Methods & Results: To uncover potential prognostic markers, we employed the weighted correlation network analysis (WGCNA) on the Chinese Glioma Genome Atlas (CGGA) 693 dataset to reveal four modules significantly associated with glioma clinical traits, primarily involved in immune function, cell cycle regulation, and ribosome biogenesis. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, we identified 11 key genes and developed a prognostic risk score model, which exhibits precise prognostic prediction in the CGGA 325 dataset. More importantly, we also validated the model in 12 glioma patients with overall survival (OS) ranging from 4 to 132 months using mRNA sequencing and immunohistochemical analysis. The analysis of immune infiltration revealed that patients with high-risk scores exhibit a heightened immune infiltration, particularly immune suppression cells, along with increased expression of immune checkpoints. Furthermore, we explored potentially effective drugs targeting 11 key genes for gliomas using the library of integrated network-based cellular signatures (LINCS) L1000 database, identifying that in vitro, both torin-1 and clofarabine exhibit promising anti-glioma activity and inhibitory effect on the cell cycle, a significant pathway enriched in the identified glioma modules. Conclusions: In conclusion, our study provides valuable insights into molecular mechanisms and identifying potential therapeutic targets for gliomas. Full article

Background: Busulfan is an FDA-approved alkylating drug used in the chemotherapy of advanced acute myeloid leukemia. The precise mechanisms by which Busulfan kills spermatogonia stem cells (SSCs) are not yet completely understood. Methods: Using a murine model, we evaluated Busulfan-induced apoptosis and DNA damage signaling between testis and ovary tissues. We executed RT-qPCR, analyzed single-nuclei RNA sequencing data and performed in situ hybridization for the localization of the gene expression in the tissues. Results: The results indicate that, in contrast to female germ cells, haploid male germ cells undergo significant apoptosis following Busulfan chemotherapy. Moreover, a gene enrichment analysis revealed that reactive oxygen species may activate the inflammatory response in part through the TNF-α/NF-κB signaling pathway. Interestingly, in the testis, the mRNA levels of TNF-α and TAF7 (TATA box-binding protein-associated factor 7) are downregulated, and testosterone levels suppressed. Mechanistically, the promoter of TNF-α has a conserved motif for binding TAF7, which is necessary for its transcriptional activation and may require further in-depth study. We next analyzed the tumorigenic function of TAF7 and revealed that it is highly overexpressed in several types of human cancers, particularly testicular germ cell tumors, and associated with poor patient survival. Therefore, we executed in situ hybridization and single-nuclei RNA sequencing, finding that less TAF7 mRNA is present in SSCs after chemotherapy. Conclusions: Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings may account for the therapeutic effects of Busulfan and underlie its potential impact on cancer chemotherapy prognosis. Full article

Aquaporins (AQPs) are highly conserved small transmembrane proteins that facilitate the transport of water and small solutes across cell membranes. Aquaglyceroporin 7 (AQP7), a significant member of the AQP family, is widely distributed throughout the body. For years, AQP7 was predominantly recognized for its role as a small-molecule transporter, facilitating the passage of small molecular substances. However, growing studies have revealed that AQP7 is also involved in the regulation of lipid synthesis, gluconeogenesis, and energy homeostasis, and it is intimately linked to a variety of diseases, such as obesity, type 2 diabetes mellitus, cardiovascular diseases, cancer, and inflammatory bowel disease. This article presents a comprehensive overview of the structure of AQP7, its regulatory mechanisms, its vital roles in both healthy and diseased states, and potential therapeutic advancements. We hope that these studies will serve as a valuable reference for the development of future treatments and diagnostic protocols targeting AQP7. Full article

c-Src is involved in multiple signaling pathways and serves as a critical target in various cancers. Growing evidence suggests that prolonging a drug’s residence time (RT) can enhance its efficacy and selectivity. Thus, the development of c-Src antagonists with longer residence time could potentially improve therapeutic outcomes. In this study, we employed molecular dynamics simulations to explore the binding modes and dissociation processes of c-Src with antagonists characterized by either long or short RTs. Our results reveal that the long RT compound DAS-DFGO-I (DFGO) occupies an allosteric site, forming hydrogen bonds with residues E310 and D404 and engaging in hydrophobic interactions with residues such as L322 and V377. These interactions significantly contribute to the long RT of DFGO. However, the hydrogen bonds between the amide group of DFGO and residues E310 and D404 are unstable. Substituting the amide group with a sulfonamide yielded a new compound, DFOGS, which exhibited more stable hydrogen bonds with E310 and D404, thereby increasing its binding stability with c-Src. These results provide theoretical guidance for the rational design of long residence time c-Src inhibitors to improve selectivity and efficacy. Full article

Lung and colon cancer (LCC) is a dominant life-threatening disease that needs timely attention and precise diagnosis for efficient treatment. The conventional diagnostic techniques for LCC regularly encounter constraints in terms of efficiency and accuracy, thus causing challenges in primary recognition and treatment. Early diagnosis of the disease can immensely reduce the probability of death. In medical practice, the histopathological study of the tissue samples generally uses a classical model. Still, the automated devices that exploit artificial intelligence (AI) techniques produce efficient results in disease diagnosis. In histopathology, both machine learning (ML) and deep learning (DL) approaches can be deployed owing to their latent ability in analyzing and predicting physically accurate molecular phenotypes and microsatellite uncertainty. In this background, this study presents a novel technique called Lung and Colon Cancer using a Swin Transformer with an Ensemble Model on the Histopathological Images (LCCST-EMHI). The proposed LCCST-EMHI method focuses on designing a DL model for the diagnosis and classification of the LCC using histopathological images (HI). In order to achieve this, the LCCST-EMHI model utilizes the bilateral filtering (BF) technique to get rid of the noise. Further, the Swin Transformer (ST) model is also employed for the purpose of feature extraction. For the LCC detection and classification process, an ensemble deep learning classifier is used with three techniques: bidirectional long short-term memory with multi-head attention (BiLSTM-MHA), Double Deep Q-Network (DDQN), and sparse stacked autoencoder (SSAE). Eventually, the hyperparameter selection of the three DL models can be implemented utilizing the walrus optimization algorithm (WaOA) method. In order to illustrate the promising performance of the LCCST-EMHI approach, an extensive range of simulation analyses was conducted on a benchmark dataset. The experimentation results demonstrated the promising performance of the LCCST-EMHI approach over other recent methods. Full article

Background: Less than 25% of gastric cancers (GC) are discovered early, leading to limited treatment options and poor outcomes (27.8% mortality, 3.7% 5-year survival). Screening programs have improved cure rates, yet post-diagnosis treatment guidelines remain unclear (systemic chemotherapy versus surgery). The optimal type of palliative surgery (palliative gastrectomy (PG), surgical bypass (SB), endoscopic stenting (ES)) for long-term outcomes is also debated. Methods: A literature review was conducted using PubMed, MEDLINE, and EMBASE databases along with Google Scholar with the search terms “gastric cancer” and “palliative surgery” for studies post-1985. From the initial 1018 articles, multiple screenings narrowed it to 92 articles meeting criteria such as “metastatic, stage IV GC”, and intervention (surgery or chemotherapy). Data regarding survival and other long-term outcomes were recorded. Results: Overall, there was significant variation between studies but there were similarities of the conclusions reached. ES provided quick symptom relief, while PG showed improved overall survival (OS) only with adjuvant chemotherapy in a selective population. PG had higher mortality rates compared to SB, with ES having a reported 0% mortality, but OS improved with chemotherapy across both SB and PG. Conclusions: Less frail patients may experience an improvement in OS with palliative resection under limited circumstances. However, operative intervention without systemic chemotherapy is unlikely to demonstrate a survival benefit. Further research is needed to explore any correlations. Full article

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug–drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit. Full article

Mdmx (Mdm4) is established as an oncogene mainly through repression of the p53 tumour suppressor. On the other hand, anti-oncogenic functions for Mdmx have also been proposed, but the underlying regulatory pathways remain unknown. Investigations into the effect of inhibitors for the NEDD8 pathway in p53 activation, human cell morphology, and in cell motility during gastrulation in Xenopus embryos revealed an anti-invasive function of Mdmx. Through stabilisation and activation of the RhoA GTPase, Mdmx is required for the anti-invasive effects of NEDDylation inhibitors. Mechanistically, through its Zn finger domain, Mdmx preferentially interacts with the inactive GDP-form of RhoA. This protects RhoA from degradation and allows for RhoA targeting to the plasma membrane for its subsequent activation. The effect is transient, as prolonged NEDDylation inhibition targets Mdmx for degradation, which subsequently leads to RhoA destabilisation. Surprisingly, Mdmx degradation requires non-NEDDylated (inactive) Culin4A and the Mdm2 E3-ligase. This study reveals that Mdmx can control cell invasion through RhoA stabilisation/activation, which is potentially linked to the reported anti-oncogenic functions of Mdmx. As inhibitors of the NEDD8 pathway are in clinical trials, the status of Mdmx may be a critical determinant for the anti-tumour effects of these inhibitors. Full article

Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. Results: In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na⁺ and Ca²⁺ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. Conclusions: These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation. Full article