Search Results (6,503)

Atherosclerosis is a chronic inflammatory cardiovascular disease that may result from the interaction between oxidative stress, immune dysregulation, and metabolic disorders. Recent studies indicate that the well-known phenolic compounds, hydroxytyrosol (HTyr) and tyrosol (Tyr) present in extra virgin olive oil, confer cardioprotection through various mechanisms of action that include antioxidant, anti-inflammatory, and metabolic regulatory properties. The gut microbiota modulates the structure, bioavailability, and bioactivity of these phenolic compounds, thereby influencing their therapeutic potential. This review explores the intricate interactions between Tyr, HTyr, and gut microbiota within the context of atherosclerosis prevention and management. We explore how gut microbial metabolism can magnify or alter the biological effects of the Tyr and HTyr, and how interindividual differences in microbiota composition may influence their efficacy. A deeper understanding of these mechanisms could support the development of precision nutrition strategies aimed at reducing the risk of atherosclerosis. Full article

To contrast the COVID-19 pandemic brought by the corona virus SARS-CoV-2, two mRNA-based anti-COVID-19 vaccines (by Pfizer-BioNTech and Moderna) were made available relatively quickly and deployed worldwide based on an emergency approval. Being considered vulnerable and at risk of infection, cancer patients have been prioritized for COVID-19 vaccination and vaccinated repeatedly because of the short time protection provided by these vaccines. Recently, a surge in the incidence and rapid progression of cancers has been observed in many countries, which could (at least partially) represent cancers undiagnosed or untreated during the pandemic. It has also been suggested that the SARS-CoV-2 itself or even the anti-COVID-19 mRNA vaccines could have contributed to the recurrence and worse clinical outcome in cancer patients, given the high incidence of COVID-19 in hospitalized patients and that these patients have been vaccinated with priority several times and in a short period. Although it appears extremely unlikely that SARS-CoV-2 and anti-COVID-19 mRNA vaccines elicit genotoxic events and cause neo-cancerogenesis in a short time, they could still cause non-genotoxic pro-carcinogenic effects by triggering an exaggerated inflammatory reaction, compromising immune homeostasis, stimulating cell proliferation, and negatively affecting cellular stress response and damage repair machinery. This could result in the promotion of regrowth of dormant micrometastases or relapses of stable minimal residual disease. Such a harmful outcome may likely result from a synergy between the virus and the vaccine, especially in multi-vaccinated and multi-infected individuals. Here, I bring the cell pathologist’s point of view and discuss the multiple possible mechanisms by which the virus and the anti-COVID-19 mRNA vaccine might favor tumorigenesis. While a causal link cannot be established at this stage, knowledge of potential carcinogenic risks could help doctors and health policymakers take the best actions to protect vulnerable patients and convince the vaccine developer to design a vaccine free from such harm. Full article

Background/Objectives: Hodgkin’s lymphoma (HL) is a cancer of the lymphatic system, the etiology of which remains partially unexplained, and environmental factors, including nutritional factors, may play an important role in its development and clinical course. The aim of this review was to examine the available literature on the impact of nutrition on the development and mortality of Hodgkin lymphoma. Methods: We conducted a literature review using databases, including publications from the last 10 years on nutrition and HL. Eventually, 3 publications were included in the review. Conclusions: Available data suggest that a diet rich in vegetables, fruits, fiber, and omega-3 fatty acids may have a protective effect, reducing the risk of developing Hodgkin’s lymphoma and improving prognosis and survival through anti-inflammatory and immune-supporting effects. On the other hand, excessive consumption of saturated fats, simple sugars and processed meat products can promote cancer transformation and worsen the course of the disease. Despite the promising results, further, well-designed prospective and interventional studies are needed to unequivocally determine the role of nutrition in the etiopathogenesis and treatment of HL. Full article

The recent rise in anti-globalization sentiment has renewed interest in how tariffs influence the location decisions of multinational enterprises (MNEs). However, these decisions have also been reshaped by ongoing geopolitical tensions-a factor that remains underexplored in the existing literature. In this study, we construct a panel dataset comprising 283,272 country-country-industry observations spanning the years 2009 to 2021. The data are drawn from the WITS, BvD, World Bank, and GDELT databases. Using fixed-effects regression, fixed-effects logit, and fixed-effects negative binomial models, we examine how MNEs respond to tariffs under varying levels of geopolitical risk. Our analysis yields three key insights. First, in contexts of low or no geopolitical risk, higher tariffs increase the likelihood of international investment by MNEs, consistent with the “tariff jumping” hypothesis. However, under high geopolitical risk, this effect disappears-regardless of tariff levels, MNEs are not more likely to invest abroad. Second, tariff increases can escalate low levels of geopolitical tension between home and host countries, further discouraging international investment. In contrast, high levels of geopolitical risk are not significantly correlated with tariff changes. Third, when low-level geopolitical tensions arise, MNEs may redirect investment to neighboring countries or major trading partners of the host country as a way to access its market indirectly. Full article

Background: Dihydromyricetin (DHM), a natural dihydroflavonol, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, its potential mechanism of action in the individualized therapy of hepatocellular carcinoma (HCC) remains unclear. Methods: Potential therapeutic targets of DHM were identified using the Swiss Target Prediction database. The overlap between these targets and differentially expressed genes in HCC was analyzed to determine therapeutic targets. A prognostic model was constructed based on these genes, and patients were stratified into high- and low-risk groups. The associations between risk scores, clinical pathological characteristics, and overall survival were analyzed using Cox regression and Kaplan–Meier survival curves. The relationships between risk score and immune cell infiltration, immunosuppressive factors, and anticancer drug susceptibility were evaluated. Results: A three-gene prognostic model was established, comprising DTYMK, MAPT, and UCK2, designated as DHM-target genes (DHMGs). Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group (p < 0.001; HR [95% CI] = 4.953 [2.544, 9.645]). Higher risk scores were correlated with more advanced tumor stages and grades. Comprehensive analysis of the tumor immune microenvironment revealed that high-risk patients exhibited significantly elevated TIDE scores, increased Treg cell infiltration, and markedly reduced stromal scores. Conclusions: This study developed a prognostic model based on the potential target genes of DHM in HCC. This model effectively stratifies HCC patients, identifying a high-risk subgroup characterized by an immunosuppressive microenvironment. These findings provide a theoretical foundation for exploring DHM as a promising natural adjuvant for cancer immunotherapy. Full article

Osteoporosis is an aging-related disease characterized by low bone mineral density and deteriorated bone structure, resulting in an increased risk of fractures. Currently, most osteoporosis therapies target osteoclasts to inhibit bone resorption, while the three FDA-approved anabolic agents include parathyroid hormone, parathyroid hormone-related protein, and anti-sclerostin antibody that promote osteoblast function. However, long-term treatment with these agents is associated with potential adverse effects and decreased therapeutic efficacy. This has prompted exploration of novel therapeutic strategies, including microRNAs (miRNAs), which are emerging as promising candidates. miRNAs have been reported to play important roles in regulating pathways involved in bone formation and resorption. In addition to their direct roles in osteoblasts and osteoclasts, miRNAs also serve as key mediators of communication between these cells, which is essential for maintaining bone homeostasis. The complexity of osteoporosis requires versatile regulators such as miRNAs that can modulate multiple biological pathways. Recent studies have demonstrated the potential of miRNA-based therapy to restore bone homeostasis in osteoporotic models. However, further studies are needed to develop tissue-specific delivery systems and evaluate long-term safety to improve the therapeutic potential of miRNAs as new osteoporosis drugs. Full article

The phenomenon of seawater flow-freezing exists during ballast water injection and drainage in polar vessels, but the heat transfer and ice evolution behaviors under low-temperature flow conditions remain unclear. This study developed a computational model for ballast tank freezing using the volume of fluid (VOF) and enthalpy–porosity method, and constructed a scaled experimental platform for the simulation model validation. Based on this model, the flow-heat transfer and ice evolution process in the ballast tank are analyzed in detail, with a focus on the influence of injection velocity, pipe diameter, and position on seawater freezing characteristics. The results show that during low-temperature water injection, phase change occurs preferentially in the tank bottom region, with ice presenting as a slurry morphology; when injection velocity increases from 0.25 m/s to 3.5 m/s, the maximum ice-phase volume fraction increases by 48.9%, indicating faster flow accelerates phase-change freezing; compared to other diameters, DN150 piping exhibits the highest turbulent kinetic energy (0.054 m²/s²) and the maximum shear stress (12.49 Pa), demonstrating optimal freezing resistance; compared to bottom injection, sidewall injection intensifies heat transfer/icing near tank walls and increases ice-clogging risk around ports. This study reveals intrinsic mechanisms of dynamic ice-blockage evolution, providing theoretical basis for anti-clogging design in polar ship systems. Full article

Background/Objectives: Chronic hepatitis C virus (HCV) remains a major public health concern in Taiwan, particularly in southern regions with high endemicity. While HCV elimination is a national priority, resources are often limited. Relying solely on broad, township-level prevalence rates is inefficient, as the true disease burden can vary dramatically at the village level. Therefore, identifying local hotspots through fine-scale mapping is critical for efficient resource allocation and targeted intervention. This study aimed to validate village-level prevalence estimates and evaluate the efficiency of a community-based, targeted screening approach utilizing this detailed prevalence data in Chiayi County. Methods: We integrated data from the Chiayi Health Bureau and Chiayi Chang Gung Memorial Hospital (2000–2015) to generate village-level risk maps for five townships: Lioujiao (LJ), Yijhu (YH), Dongshih (DS), Taibao (TB), and Lucao (LC). Between 2018 and 2021, we conducted door-to-door community screening using anti-HCV testing with reflex HCV antigen (Ag) testing. Anti-HCV/HCV Ag prevalence, number needed to test (NNT), and linkage-to-care rates were calculated to validate prevalence estimates and assess screening efficiency. Results: Among 3910 participants, anti-HCV prevalence ranged from 5.4% (TB) to 8.7% (DS). Estimated and observed village-level prevalence showed moderate-to-strong correlation (r = 0.696–0.830, p < 0.001). Screening efficiency was highest in DS (NNT = 21) and lowest in TB (NNT = 42). Of 132 antigen-positive individuals, 131 (99.2%) initiated direct-acting antiviral therapy. Conclusions: The village-level risk maps accurately predicted local HCV burden, enabling targeted screening with high diagnostic yield and near-complete treatment uptake. This approach maximizes resource efficiency and may serve as a scalable model for advancing Taiwan and the WHO’s 2030 HCV elimination goals. Full article

Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and molecular traits. Standard treatments like surgery, chemotherapy, and radiation have limited effectiveness and high toxicity. Targeted therapies, including poly (ADP-ribose) polymerase PARP inhibitors, anti-angiogenics, and immune checkpoint inhibitors (ICIs), face obstacles such as adaptive resistance and microenvironmental barriers that affect drug delivery and immune responses. Factors in the tumor microenvironment, such as dense stroma, hypoxia, immune suppression, cancer stem cells (CSCs), and angiogenesis, can reduce drug efficacy, worsen prognosis, and increase the risk of recurrence. Research highlights impaired immune function in ovarian cancer patients as a contributor to recurrence, emphasizing the importance of immunotherapies to target tumors and restore immune function. Preclinical studies and early clinical trials found that natural killer (NK) cell-based therapies have great potential to tackle ovarian tumors. This review explores the challenges and opportunities in treating ovarian cancer, focusing on how NK cells could help overcome these obstacles. Recent findings reveal that engineered NK cells, unlike their primary NK cells, can destroy both stem-like and differentiated ovarian tumors, pointing to their ability to target diverse tumor types. Animal studies on NK cell therapies for solid cancers have shown smaller tumor sizes, tumor differentiation in vivo, recruitment of NK and T cells in the tumor environment and peripheral tissues, restored immune function, and fewer tumor-related systemic effects—suggesting a lower chance of recurrence. NK cells clinical trials in ovarian cancer patients have also shown encouraging results, and future directions include combining NK cell therapies with standard treatments to potentially boost effectiveness. Full article

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Background/Objectives: Intolerable postoperative pain perception (IPPP) may occur in patients undergoing vitreoretinal surgery (VRS), while general anesthesia (GA) is often preferred over regional techniques due to multiple contraindications. Intraoperative administration of intravenous rescue opioid analgesics (IROA) during GA increases the risk of perioperative adverse events; however, this requirement can be reduced through preventive analgesia. The Adequacy of Anesthesia (AoA) concept, based on entropy EEG and the Surgical Pleth Index (SPI), allows real-time titration of IROA to maintain optimal nociception/anti-nociception balance and create comparable intraoperative conditions across patients. This study aimed to identify risk factors for IPPP after VRS performed under AoA-guided GA combined with intravenous preventive analgesia using COX-3 inhibitors. Methods: A total of 165 patients scheduled for VRS were randomized to receive AoA-guided GA combined with intravenous preventive analgesia using either paracetamol plus metamizole, paracetamol alone, or metamizole alone. Results: Data from 153 patients were analyzed. Neither age, body mass index, smoking status, arterial hypertension, diabetes mellitus, intraoperative noxious maneuvers, demand for IROA, nor length of surgery correlated with the incidence of IPPP under AoA-guided GA. The combination of paracetamol and metamizole resulted in the lowest rate of IPPP among all groups. Conclusions: AoA-guided GA combined with COX-3 inhibitors appears to standardize intraoperative nociception/anti-nociception balance in patients undergoing VRS, effectively mitigating most known risk factors for IPPP, with female sex independently associated with its occurrence. We recommend the optimization of perioperative pharmacotherapy through individualized AoA-guided GA with intravenous COX-3 inhibitors to minimize IPPP incidence. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy. Full article

Background/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder affecting almost 10% of the general population, characterized by recurrent abdominal pain and altered bowel habits. Its pathophysiology is incompletely understood, but it is established that symptoms result from an interplay between several environmental- and patient-related factors. This study aimed to analyze the influence of a widespread shift in lifestyle habits and multidimensional stress on IBS manifestations. Methods: An online survey was administered during the COVID-19 lockdown in 2020 to three groups of people representative of the general population. The survey contained questions regarding socio-demographic data, dietary habits, alcohol, smoking, physical activity, sleeping, working activities, stress level, and the characteristics of gastrointestinal symptoms related to both the pre-pandemic period and the lockdown period. The definition of IBS was based on the Rome IV criteria. Multivariate analyses were used to evaluate the association between environmental variables and the occurrence/resolution of IBS. Results: A total of 2735 participants were enrolled. Among them, 122 patients (46.2%) reported symptoms’ improvement during the observation period, while 118 previously healthy subjects (4.8%) developed IBS symptoms. Reduced general stress (OR = 2.2, 95%CI 1.1–4.6, p = 0.029), increased fiber intake (OR = 2.8, 95%CI 1.6–5.0, p < 0.001), and increased hours of sleep (OR = 2.0, 95%CI 1.1–3.8, p = 0.031) were associated with a high probability of IBS resolution, while increased anxiolytic pill intake (OR = 0.14, 95%CI 0.04–0.46, p = 0.001) showed a low likelihood of IBS resolution. Reduced physical activity (OR = 2.0, 95%CI 1.3–3.2, p = 0.002), increased anti-inflammatory effects (OR = 2.4, 95%CI 1.4–4.1, p = 0.002), anxiolytic pill intake (OR = 3.5, 95%CI 2.1–5.9, p < 0.001), and increased work-related stress (OR = 1.8, 95%CI 1.2–2.8, p = 0.009) were risk factors for IBS symptoms’ occurrence. Reduced alcohol consumption was a protective factor (OR = 0.5, 95%CI 0.3–0.8, p = 0.006). The resolution of IBS did not affect upper gastrointestinal functional symptoms (OR = 0.2, 95%CI 0.1–0.3, p < 0.001). Conclusions: The widespread lifestyle change forced by the pandemic created a protective “Cocoon Effect”, resulting in a beneficial effect in almost half of patients with IBS. Our findings provide large-scale evidence that environmental factors play a pivotal role in the pathophysiology of IBS. Specifically, stress levels, fiber intake, sleep patterns, and alcohol consumption are key modifiable drivers of symptom occurrence and resolution. Full article

In freshwater fish, group behavior is ecologically critical for daily activities such as predator avoidance. However, species with varying shoaling preferences exhibit divergent behavioral responses under different environmental conditions. This study investigated the behavioral responses of three shoaling species (Moenkhausia costae, Puntius tetrazona, and Myxocyprinus asiaticus) and three non-shoaling species (Trichogaster trichopterus, Micropterus salmoides, and Cichlasoma managuense) to simulated predation in either an open arena or a six-arm maze with shelter available. Our findings reveal that, in open water, shoaling species employ a dual strategy against predators: maintaining high group cohesion while increasing swimming speed and acceleration. This exploits the confusion effect to mitigate individual predation risk. In contrast, non-shoaling species do not engage in evasive maneuvers; instead, they adopt a cryptic strategy by minimizing activity and often freezing in place to avoid detection. In the six-arm maze, shoaling species consistently employed group coordination strategies, whereas non-shoaling species primarily relied on shelter concealment or reduced activity. Notably, shoaling species maintained high cohesion, synchronization, and activity levels across both open and complex habitats, using coordinated movement to facilitate collective escape. Together, our findings demonstrate that habitat complexity and social tendencies jointly determine how fishes trade off risk and safety. This work provides new insights into the adaptive evolution of social behavior in dynamic aquatic ecosystems. Full article

Background: The development of anti-drug antibodies (ADAs) and resulting immune complexes are key mechanisms behind the secondary loss of response to adalimumab in Crohn’s disease (CD). Despite their clinical importance, routine immunogenicity assays are limited, underscoring the need for alternative predictive approaches. Objective: This study aimed to develop interpretable artificial neural network (ANN) models to predict immune complex formation and estimate serum adalimumab levels using routinely available clinical and laboratory data from CD patients. Methods: A prospective analysis was performed on 58 CD patients on maintenance adalimumab. Immune complexes and serum adalimumab were measured via ELISA and lateral flow assays. ANN and ensemble regression models were trained on demographic, clinical, and inflammatory data, with performance evaluated by five-fold cross-validation. Interpretability was enhanced using Garson’s algorithm and permutation importance. Results: The ANN-based classification model accurately predicted ADA immune complex formation, achieving an accuracy of 77.47% and an area under the curve (AUC) of 82.63%. The main predictive variables included extraintestinal manifestations, perianal disease, disease behavior, and age at diagnosis. For estimating serum adalimumab levels measured by ELISA, the model performed modestly (accuracy 59.89%, AUC 79.72%), incorporating factors such as Montreal classification, perianal disease, C-reactive protein, immunosuppressant use, and disease duration. Conclusions: Interpretable ANN models robustly predict anti-adalimumab immune complexes and, to a lesser extent, serum adalimumab, using clinically available data, including perianal disease. This proof-of-concept study is limited by the relatively small, single-center dataset (n = 58), which may affect model generalizability and increase the risk of overfitting. External validation in larger and multicenter cohorts is required before clinical implementation. Full article