Search Results (993)

Background/Objectives: Irritable bowel syndrome (IBS) is primarily treated via dietary modifications. Several diets have been shown to improve symptoms with similar efficacy. Other aspects of IBS, such as insufficient nutrient intake and being overweight, should also be considered when planning treatment options. The present scoping review aimed to identify various diets investigated in IBS-related clinical trials and to map the measured outcomes. Methods: We performed a systematic search of three databases: PubMed, Embase, and CINAHL Ultimate. Our search was limited to papers published between January 2000 and February 2026, and included human studies published as peer-reviewed original articles in English that described dietary interventions in adult patients (≥18 years) with IBS. Results: The titles and abstracts of 1261 studies were screened; 1147 studies were excluded; and 114 full-text articles were assessed for eligibility. Excluding articles outside the scope of our research resulted in a total of 71 included articles from 57 unique clinical trials. The most common interventions were low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) (n = 43), traditional dietary advice (n = 13), and gluten-free diets (n = 11). The most common primary outcomes were the effect on IBS symptoms (n = 48), efficacy in terms of improving quality of life (n = 10), psychological well-being (n = 7), nutrient intake (n = 7), and adherence/applicability/feasibility to the diet (n = 7). Conclusions: In conclusion, the most studied dietary intervention in IBS was low FODMAP, and an effect on GI symptoms was the most common outcome. Considering other conditions associated with IBS, the effects on anthropometric, endocrine, metabolic, and nutritional parameters should also be evaluated. Full article

Cancer has become a major global health threat due to its high incidence and mortality. However, the development of anti-cancer drugs is limited by high costs, long cycles, and low success rates, slowing the progress of new treatments. As a method that simulates human cognitive functions, artificial intelligence (AI) has greatly improved the efficiency of drug development. Machine learning is a core part of AI and supports applications such as natural language processing and computer vision. This paper reviews recent advances in AI for optimizing anti-cancer drug discovery, development, and medication therapy management. First, we highlight the applications of AI in target identification, druggability assessment, drug screening, and repurposing. Second, we detail how AI optimizes drug combination therapy and clinical trial design. Finally, we describe the role of AI in treatment management, including nanoparticle delivery systems, personalized dosing, and adaptive therapy. AI greatly streamlines anti-cancer drug development and provides new directions for precision cancer therapy. Full article

Liver transplantation remains the definitive treatment for end-stage liver disease and acute liver failure, yet a critical and persistent shortage of donor organs results in thousands of preventable deaths annually worldwide. Xenotransplantation has emerged as a potential solution to this structural deficit. This narrative review traces the evolution of liver xenotransplantation, from early non-human primate trials in the 1960s through the application of CRISPR/Cas9-driven multi-gene editing platforms in contemporary porcine donors. The immunological barriers that drove the transition from primate to porcine donors are examined, including hyperacute rejection mediated by anti-α-Gal antibodies, coagulation dysregulation and xenograft thrombotic microangiopathy. The genetic engineering strategies underlying current triple-knockout, ten-gene-edited donor pigs are reviewed alongside the preclinical non-human primate evidence establishing biological feasibility. The three pig-to-human liver xenotransplantation studies published between 2025 and 2026 are then analyzed, encompassing heterotopic auxiliary transplantation in a brain-dead decedent, extracorporeal liver cross-circulation and the first auxiliary liver xenotransplantation in a living recipient with a documented 171-day survival. These cases collectively provide preliminary evidence supporting proof-of-concept for porcine hepatic bridging therapy, with current evidence supporting a role for xenogeneic liver support as a temporary bridge to recovery or allotransplantation rather than definitive organ replacement. Xenograft thrombotic microangiopathy is identified as the principal remaining biological barrier, and the substantial translational challenges, including reproducibility, scalability and regulatory readiness that must be resolved before broader clinical application can be considered. Full article

Androgens regulate skeletal muscle, bone, erythropoiesis, and male reproductive function via the androgen receptor (AR), a ligand-dependent transcription factor. Pharmacologic modulation of AR has been pursued for clinical and non-medical purposes. Anabolic androgenic steroids (AAS), synthetic testosterone derivatives, act as full AR agonists, broadly activating multiple tissues. While effective in promoting muscle growth and strength, AAS cause well-known adverse effects, including hypothalamic–pituitary–gonadal (HPG) axis suppression, dyslipidemia, hepatotoxicity, cardiovascular disease, tendon injury, and neuropsychiatric disturbances. Selective androgen receptor modulators (SARMs) aim to stimulate AR in muscle and bone while minimizing androgenic effects in prostate and skin. They induce ligand-specific AR conformations, altering coactivator and corepressor recruitment, and avoiding metabolism by 5α-reductase or aromatase. Preclinical studies show favorable anabolic-to-androgenic ratios, but clinical translation is limited. Early human trials report modest lean mass gains, variable functional outcomes, and dose-dependent testosterone suppression. Emerging evidence also suggests cardiotoxicity, tendon injury, and liver toxicity, though long-term effects are unclear. Pharmacokinetically, SARMs have predictable oral absorption and moderate half-lives, enabling once-daily dosing, unlike AAS. This review compares AAS and SARMs in molecular mechanisms, pharmacokinetics, and safety. While SARMs offer partial tissue selectivity and reduced adverse effects, risks remain, and long-term safety is uncertain. Regulatory oversight is limited, and non-medical use is rising. Preclinical and clinical studies are needed to clarify whether SARMs can separate anabolic benefits from androgenic toxicity and inform safe clinical application. Full article

Background/Objectives: The treatment of gynecologic malignancies has moved towards a precision medicine model with an approach to prognostication and management based on biomarker testing. The objective of this review is to describe the current landscape of biomarker testing in gynecologic cancer including clinical implications and the approach to testing. Methods: A review of the literature was performed that included published clinical trials which utilized biomarker testing as part of inclusion/exclusion criteria, prospective trials that addressed the application and scoring of biomarkers utilized in gynecologic cancers, prospective clinical trials that utilized biomarker findings to determine management, and national or society guidelines for the scoring of biomarkers and treatment of gynecologic cancers. Findings: The use of biomarker testing as part of the management of gynecologic cancers is the standard of care for both treatment and prognostication. In endometrial cancer, biomarker testing has been incorporated into the staging system and impacts treatment in both the upfront and recurrent setting. Specific biomarkers of interest for endometrial cancer include estrogen receptor (ER), progesterone receptor (PR), DNA Polymerase Epsilon (POLE), mismatch repair proteins (MMR), and Human Epidermal growth factor Receptor-2 (HER2). In ovarian cancer, biomarker testing is primarily utilized in the recurrent setting to guide management of platinum-resistant ovarian cancer with a specific focus on targeted therapy utilizing antibody drug conjugates (ADCs) and immunotherapy. Immunotherapy has become an important component of therapy for cervical cancer and Programmed death-ligand 1 (PD-L1) testing is a key biomarker in determining treatment. Conclusions: The utilization of appropriate assays and processes to accurately assess the status of biomarkers in the pathology laboratory is crucial to the treatment of gynecologic malignancies in the precision medicine era. Full article

Traditional disease management, which is based on the application of synthetic chemical products, has negatively affected human health and the environment. A sustainable approach based on the application of natural compounds and microorganisms is potentially better for consumer health. Thus, the aim of this study was to evaluate the efficacy of plant-based and/or organic products against soilborne fungal pathogens of tomato. A preliminary in vitro experiment was performed to select potential putative inhibitory products (PIPs) and fungal pathogens that were then used in an in vivo experiment conducted inside a greenhouse that mimics real-world field conditions. For the greenhouse experiment, bergamot and pomegranate wastes and the commercial product EP5 were selected as the PIPs to control Agroathelia rolfsii, Fusarium oxysporum and Sclerotinia sclerotiorum growth. Each pot was artificially inoculated three days before the low-dose treatment, and one tomato seedling was transplanted into each pot four days after the treatment. Data regarding the phytosanitary status of the plants and roots, as well as their length and weight, were collected after 45 days, and the results obtained demonstrate that plant-derived products were able to mitigate fungal diseases, with pomegranate waste being the most effective. Also, the EP5 product, as a resistant inducer, was able to significantly improve the natural defense of tomato plants, resulting in it being the best PIP used. Mycological analyses were performed on the roots to assess the presence of inoculated fungal pathogens after natural product treatment. Overall, the results confirm that the PIPs are suitable for crop management, but the outcomes are variable. In general, pomegranate waste and EP5 significantly protected the roots against fungal attacks, while bergamot waste showed lower efficacy. This trend was not observed for plant length and weight, as the treated plants showed results similar to those of the untreated controls. In conclusion, natural products are a valid alternative to chemicals, as they demonstrate both efficacy and safety, but their potential should be further investigated in field trials. Full article

Mercury (Hg) is a ubiquitous element in the environment that may pose a threat to human health due to its toxicity, high mobility through the food chain, and long-lasting persistence. Organic Hg compounds, particularly methylmercury, are more toxic than inorganic mercury due to their easy absorption and persistent retention within the organism. Although natural attenuation can occur in soil through various processes, excessive levels of Hg cause pollution that can adversely affect agricultural soil, making remediation necessary to either remove or stabilize Hg within the soil. This review primarily aims to summarize key remediation strategies—chemical, biological, and physical—developed in recent years for agricultural soil remediation. It discusses the influencing factors, advantages, limitations, mechanisms, and practical applications of these soil remediation technologies. The published literature focuses on identifying plant species and microorganisms capable of remediating Hg-contaminated soils. Emerging amendments, such as biochar and nanomaterials, have been tested for treating mercury (Hg)-polluted soils primarily by immobilizing mercury and reducing its bioavailability and methylation. Ex situ remediation technologies are effective for Hg-contaminated soils but are often costly, labor-intensive, detrimental to soil quality, and generate hazardous secondary waste. In contrast, in situ technologies treat Hg directly within the soil, preserving the soil matrix and its biota. According to the literature, remediation of Hg-contaminated agricultural soils can be compatible with food crop production only if the bioavailable Hg fraction is sufficiently reduced and crop uptake remains below food safety limits. The gap between laboratory trials and actual field applications in Hg-contaminated soil remediation mainly arises from differences in scale, complexity, and the uncertainty of real-world conditions, which often reduce the efficiency and predictability of treatments. This review aims to provide a practical reference for improving the effective remediation of Hg-contaminated soils in the future. Full article

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a central role in the regulation of cell cycle progression and represent important therapeutic targets in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer. The introduction of selective CDK4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, in combination with endocrine therapy, has significantly improved clinical outcomes and has become a standard treatment strategy in both metastatic and high-risk early-stage disease. Nevertheless, treatment resistance and disease progression remain major clinical challenges. A deeper understanding of the structural characteristics of CDK4/6 and the molecular basis of inhibitor binding is therefore essential for improving therapeutic strategies and guiding the development of new targeted agents. This review provides an integrated overview of the structural features of CDK4/6 and their role in cell cycle regulation, summarizes the clinical development and major clinical trials of currently approved CDK4/6 inhibitors, and discusses recent computational studies investigating inhibitor binding and conformational dynamics. Particular attention is given to the application of in silico approaches, including molecular docking, molecular dynamics simulations, and binding free-energy calculations, which provide insights into mechanisms of therapy resistance and potential strategies to overcome them and support the identification and optimization of novel CDK4/6-targeted therapeutic candidates. By integrating structural, clinical, and computational perspectives, this review highlights current knowledge and emerging directions in CDK4/6 research that may advance the development of more personalized therapies for HR+/HER2− breast cancer, while accounting for both intrinsic and de novo resistance mechanisms. Full article

This paper presents a simulation-based methodology for automated tuning of a triple-loop controller (steering, throttle, and braking) for a Dallara single-seater race car. The approach targets on-track driving at handling limits, where strong nonlinearities and coupled dynamics dominate, treating the vehicle as a black box. Five controller gains are optimized via derivative-free pattern search, using reference trajectories from a professional driver in a Driver-in-the-Loop (DiL) simulator. Human-likeness is promoted by penalty terms on state and control trajectories while maximizing distance over a fixed horizon as a proxy for lap-time reduction. The application uses a high-fidelity multibody vehicle model with realistic tire, suspension, and actuator dynamics in the DiL environment, rather than simplified single-track representations. Contributions are: (i) effective application of derivative-free optimization to complex, high-dimensional, black-box vehicle systems; and (ii) a systematic, reproducible procedure for automatic tuning of controller parameters with a predetermined architecture to reproduce a professional driver’s performance and embed human-likeness. Optimization required approximately 2.4 h. Results show that the optimized controller improves track coverage by 63.6 m (1.1% increase) compared to manual tuning while maintaining a realistic driving style, offering a more systematic and reliable solution than manual, trial-and-error calibration. Full article

Additive manufacturing has recently become a key enabling technology in industrial fields, ranging from customized products for everyday usage to aerospace applications and small-batch industrial tooling. The future prospects extend up to the biofabrication of human organs. Ensuring the quality and repeatability of this process requires a systematic and comprehensive investigation of the underlying physical phenomena. In particular, melt-pool evolution is a critical feature, since irregularities in its spatial profile can influence microstructural evolution and weaken the integrity of the manufactured part. Microscale defects arising from balling and keyhole phenomena, often associated with recoil pressure, can severely degrade the quality of the resulting scanned track. This paper reviews the current state of optical approaches for melt-pool characterization and feature monitoring relevant to industrial laser additive manufacturing for process control and quality improvement, with a special focus on pyrometry and high-speed imaging. A single high-speed camera was generally used in experiments for melt-pool feature extraction, but two cameras were used to bypass emissivity values, which are otherwise difficult to obtain. Mathematical models were introduced to provide complementary information about melt-pool features, while artificial intelligence algorithms were used in other cases to process optical information. New melt-pool imaging databases and classifiers are expected in the near future to enable fast selection of appropriate process parameter windows, eliminating costly trial-and-error experiments. Full article

Exerkines are released in response to physical exercise and play a key role in promoting health, such as taking part in modulating brain morphology and function. Expression levels of some of them are associated with an increase in neuroplasticity and a decrease in the risk of brain-related diseases such as dementia and depression. Therefore, our objective is to investigate the response of exerkines in healthy individuals and its potential to promote brain health. The search was performed in five databases. Randomized controlled trials of humans and animals of all ages who performed acute and/or long-term exercise and assessed the effects of exerkines were included. Human data were used for quantitative analysis, and animal experiments were included as part of the qualitative analysis. No meta-analyzes were conducted on animal data; preclinical findings are presented solely to contextualize mechanisms and are not used for clinical inference. Eventually, the sample consisted of 3321 individuals, with an age range from 10 to 89 years. Meta-analysis reveals that both acute and chronic exercise induced increases in the brain-derived neurotrophic factor and insulin-like growth factor 1 in older adults. Other exerkines such as cathepsin B and vascular endothelial growth factor have also demonstrated potential power for brain health. In conclusion, physical exercise by altering the levels of exerkines may be a feasible strategy for healthy individuals aiming at healthy aging of the brain. Moreover, it is advisable to analyze additional exerkines or multiple simultaneous applications to assess the cerebral effects during physical exercise. PROSPERO registration number: CRD42023438803. Full article

Artificial intelligence (AI) is rapidly reshaping head and neck surgical oncology by augmenting decision-making across the full perioperative continuum. This state-of-the-art review aims to provide head and neck surgical oncologists with a conceptual framework for understanding and critically appraising AI tools entering clinical practice, summarizing how machine learning, deep learning, and generative AI are being integrated into contemporary surgical workflows. Preoperative applications include detection of occult nodal metastasis and extranodal extension. Intraoperative innovations include augmented reality-assisted navigation, real-time margin assessment, and improving visual clarity and tissue handling for robotic platforms. Postoperatively, AI can predict complications like free flap failure and oncologic outcomes. Large language models are being operationalized for clinician-facing applications such as documentation and inbox support, as well as patient-facing education. Despite promising results, broad clinical deployment remains limited by concerns about privacy, validation, reliability, safety, and ethics. Widespread adoption will require prospective clinical trials, robust governance, and human-centered workflows that ensure AI remains a safe, assistive copilot. Full article

Food-grade emulsion gels are increasingly being used to create food products with innovative properties and functional attributes. However, the rapid expansion of research in this area has outpaced the establishment of standardized methodologies, leading to challenges in reproducibility and cross-study comparability. This review addresses this critical gap by providing a comprehensive set of methodological guidelines for the reliable preparation, characterization, and evaluation of food-grade emulsion gels intended for gastrointestinal-targeted nutrient delivery. Initially, systematic approaches for emulsion gel preparation are reviewed, focusing on formulation parameters and processing conditions that dictate the structure and function of these products. A multi-scale framework for physicochemical characterization of emulsion gels is then presented, encompassing structural, rheological, mechanical, thermal, and fluid-holding properties. Guidelines for testing the performance of emulsion gels under simulated food matrix and storage conditions are then given, including methods to monitor bioactive degradation. Furthermore, best practices for evaluating the gastrointestinal behavior of emulsion gels using standardized in vitro digestion models, and subsequent biological evaluation using cell-based assays, animal models, and human trials are discussed. This review concludes that standardized fabrication, characterization, digestion, and reporting protocols are critical for improving reproducibility and comparability across studies and for advancing food-grade emulsion gels toward reliable functional food applications. Full article

The African catfish (Clarias gariepinus) is an important aquaculture species in the Philippines, but it exhibits reproductive dysfunctions in captivity due to the absence of natural spawning cues and culture-induced stress. In hatcheries, sperm collection often requires sacrificing male breeders, limiting breeding program applications, and threatening genetic diversity. This study evaluated and optimized hormonal induction protocols to enhance spermiation and fertilization success in male C. gariepinus. Two experimental trials were conducted under controlled hatchery conditions. In Trial 1, human chorionic gonadotropin combined with a dopamine antagonist (hCG + DA; 5000 IU·kg⁻¹ BW + 5 mg·kg⁻¹ BW) and Ovaprim (1.0 mL·kg⁻¹ BW) significantly increased circulating testosterone and estradiol levels, spermiation index, and fertilization outcomes (embryo viability, hatching, and larval survival). In Trial 2, medium to low doses of hCG + DA (3000–5000 IU·kg⁻¹ BW + 5 mg·kg⁻¹ BW) and Ovaprim (0.75–1.0 mL·kg⁻¹ BW) yielded the best performance in terms of hormone levels, spermiation index, and fertilizing capabilities. The presence of a dopamine antagonist (DA) likely contributed to the efficacy of the treatments, since dopamine suppresses the secretion of gonadotropin-releasing hormone (dopaminergic inhibition), and DA counteracts this effect, increasing LH and FSH levels necessary for gametogenesis. Taken together, these results highlight the potential of optimized hormonal protocols to mitigate reproductive dysfunctions in male C. gariepinus in aquaculture settings. Further studies should refine dose combinations, assess the long-term health of broodstock, and evaluate cost-effectiveness to support sustainable broodstock management and genetic conservation. Full article

Aging is closely linked to oxidative stress and inflammation. This review provides a critical overview of the antioxidant compounds present in apple pomace and explores how they may mitigate age-related oxidative damage and inflammatory responses. We focus on the nutritional profile of apple pomace including its macro- and micronutrients, with particular focus on polyphenols, such as procyanidin tannins, quercetin glycosides (rutin, quercetin-3-glucoside), phloridzin, dietary fiber, vitamins, and lipids alongside current techniques for isolating its bioactive components. Special attention is given to biological pathways through which these compounds influence aging: redox regulation via Nrf2, inflammatory modulation via NF-κB, and metabolic regulation via AMPK, SIRT1 and PI3K/Akt/mTOR. Evidence from in vitro cellular models (HepG2, CCD-986Sk fibroblasts), in vivo rodent studies and limited human pilot trials is summarized, as well as existing and emerging applications of apple pomace in functional foods, cosmeceuticals, and other sectors. Finally, we discuss the challenges and future opportunities in harnessing this by-product of the food industry. Although clinical data remain limited, preclinical findings support the repurposing of apple pomace as a sustainable functional ingredient contributing to healthier aging and circular economy goals. Future long-term randomized controlled trials are necessary to confirm efficacy in humans. Full article