Search Results (851)

Background: Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort. Full article

Many commercially available medications are often unapproved or unavailable in suitable dosage forms for specific patient populations, particularly infants and children. This necessitates the use of extemporaneously compounded formulations to deliver individualized doses based on body weight or body surface area, and when a medication is unavailable at an appropriate concentration or contains excipients potentially unsafe for certain patients. Extemporaneous compounding is required for oral liquids when patients are unable to swallow tablets or capsules. It is also needed for topical preparations and sterile dosage forms when commercial products are unavailable. Across regions, practices follow national pharmacopeial standards for both sterile and non-sterile compounding. Stability factors influencing the safety and efficacy of compounded formulations must be carefully considered when assigning appropriate beyond-use dates. While stability information is available for some medications in monographs, peer-reviewed literature, prescribing information, and investigator’s brochures, such data is often lacking for many compounded preparations. Emerging extemporaneous formulations—such as orodispersible films, nanoparticle systems, and 3D-printed compounds—offer potential advantages over traditional compounded formulations but present unique challenges to widespread implementation. Despite the justified clinical need for extemporaneous compounding, significant barriers remain, including limited access to medications, insufficient compounding expertise or resources, gaps in pharmacokinetic and safety data, and regulatory constraints. This review critically appraises the current state of extemporaneous compounding—drawing primarily on the United States of America frameworks—and highlights its continued necessity, associated challenges, and pragmatic solutions for advancing personalized pharmacotherapy across pediatric age groups worldwide. Full article

Ionic liquids (ILs) have emerged as multifunctional compounds with low volatility, high thermal stability, and tunable solvation capabilities, making them highly promising for biomedical applications. First explored in the late 1990s and early 2000s for enhancing the thermal stability of enzymes, antimicrobial agents, and controlled release systems, ILs have since gained significant attention in drug delivery, antimicrobial treatments, medical imaging, and biosensing. This review examines the diverse functions of ILs in contemporary therapeutics and diagnostics, highlighting their transformative capabilities in improving drug solubility, bioavailability, transdermal permeability, and pathogen inactivation. In drug delivery, ILs improve solubility of bioactive compounds, with several IL formulations achieving substantial solubility enhancements for poorly soluble drugs. Bio-ILs, in particular, show promise in enhancing drug delivery systems, such as improving transdermal permeability. ILs also exhibit significant antimicrobial and antiviral activity, offering new avenues for combating resistant pathogens. Despite their broad potential, challenges such as cytotoxicity, long-term metabolic effects, and the stability of ILs in physiological conditions persist. While much research has focused on their physicochemical properties, biological activity and in vivo studies are still underexplored. The future directions for ILs in biomedical applications include the development of bioengineered ILs and hybrid ILs, combining functional components like nanoparticles and polymers to create multifunctional materials. These ILs, derived from renewable resources, show great promise in personalized medicine and clinical applications. Further research is necessary to evaluate their pharmacokinetics, biodistribution, and long-term safety to fully realize their biomedical potential. This study emphasizes the potential of ILs to transform therapeutic and diagnostic technologies by highlighting present shortcomings and offering pathways for clinical translation, while also debating the need for continuous research to fully utilize their biomedical capabilities. Full article

Background/Objectives: Snakebite envenoming remains a critical yet frequently under-recognized cause of mortality in many parts of the world, particularly in tropical and rural areas where access to timely medical care and accurate post-mortem investigation is limited. While clinical and epidemiological data on snakebites have been extensively studied, the forensic characterization of fatal envenomations remains fragmentary and inconsistently documented. This review aims to synthesize the existing literature on autopsy-confirmed snakebite deaths, focusing on the pathological and toxicological evidence that supports cause-of-death determinations in forensic settings. Methods: A comprehensive search of the PubMed NCBI databases identified nine relevant studies, including case reports, retrospective analyses, and systematic reviews. Results: Across these reports, a range of lethal mechanisms were identified, including venom-induced consumption coagulopathy (VICC), acute renal failure (frequently in the setting of rhabdomyolysis and acute tubular necrosis), neurotoxic respiratory arrest, multi-organ necrosis, and myocardial infarction. Histological findings frequently revealed glomerular and tubular necrosis, pulmonary edema and/or hemorrhage, pituitary and adrenal hemorrhage, and cerebral ischemic changes. Toxicological confirmation was achieved in several cases using ELISA and liquid chromatography–mass spectrometry (LC–MS/MS), underscoring the importance of biochemical validation in post-mortem diagnosis and the value of analytical tools beyond ELISA (e.g., immunoaffinity LC–MS/MS, venom-specific immunohistochemistry, zymography for SVMP activity). Conclusions: Our findings highlight the variability in venom effects across snake families—particularly Viperidae, Elapidae, and Lamprophiidae/Atractaspididae—and emphasize the indispensable role of forensic autopsy in distinguishing snakebite envenoming from other causes of sudden or unexplained death. However, significant limitations persist, including inconsistent autopsy protocols, lack of species-specific venom assays, and poor integration of toxicological methods in routine forensic practice. Addressing these gaps through standardized forensic guidelines and improved access to diagnostic tools is essential for enhancing the accuracy of death investigations in envenoming-endemic regions. Full article

Dendropanax morbifera (DM; “Hwangchil”) is an evergreen tree native to southern Korea and Jeju Island, traditionally used for detoxification, anti-inflammatory, immunomodulatory, and neuroprotective purposes. Recent studies indicate that DM extracts and their constituents exhibit a broad range of biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, antidiabetic, hepatoprotective, and neuroprotective effects. Phytochemical investigations have revealed a chemically diverse profile comprising phenolic acids, flavonoids, diterpenoids, triterpenoids—most notably dendropanoxide—and polyacetylenes, with marked variation in compound distribution across plant parts. Despite this progress, translational application remains constrained by the lack of standardized extraction protocols, substantial variability in high-performance liquid chromatography (HPLC) methodologies, and limited mechanistic validation of reported bioactivities. This review proposes an integrated framework that links extraction strategies tailored to compound class and plant part with standardized C18 reverse-phase HPLC conditions to enhance analytical reproducibility. In parallel, in silico target prediction using SwissTargetPrediction is applied as a hypothesis-generating approach to prioritize potential molecular targets for subsequent experimental validation. By emphasizing methodological harmonization, critical evaluation of evidence levels, and systems-level consideration of multi-compound interactions, this review aims to clarify structure–activity relationships, support pharmacokinetic and safety assessment, and facilitate the rational development of DM-derived materials for medical, nutritional, and cosmetic applications. Full article

Electromagnetic pumps are developed for industrial, medical and scientific applications, moving electrically conductive liquids and molten solder in electronics manufacturing using electromagnetism instead of mechanical parts. This study presents a comprehensive thermal analysis of an electromagnetic diaphragm pump, focusing on the influence of operating current, permanent magnet switching speed, and cooling conditions on pumping performance. The pump utilizes a flexible diaphragm embedded with a permanent neodymium magnet, which interacts with time-varying magnetic fields generated by electromagnets to drive fluid motion. Temperature monitoring is conducted using a waterproof DS18B20 sensor and an uncooled FLIR A325sc infrared camera, allowing accurate mapping of thermal distribution across the pump surface. Experimental results demonstrate that higher current and increased magnet switching speed lead to faster temperature rise, impacting the volume of fluid pumped. Incorporation of an automatic cooling fan effectively reduces coil temperature and stabilizes pump performance. Polynomial regression models describe the relationship between temperature, pumped liquid volume, and magnet switching speed, providing information to optimize pump operation and cooling strategies. The novel relationship between temperature and the volume of the pumped liquid is considered as a fourth-degree polynomial. In particular the model describes a quantitative evaluation of the effect of heating on pumping efficiency. An initial increase in temperature correlates with a higher pumped volume, but excessive heating leads to efficiency saturation or even decline. Indeed, mathematical dependencies are crucial in mechanical pump engineering for analyzing physical phenomena; this is achieved by using a mathematical equation to define how different physical variables are related to each other, enabling engineers to calculate performance and optimize the pump design. Full article

Conventional dental materials with organised crystal structures exhibit limitations in corrosion resistance, bioactivity, and drug delivery capability. In contrast, amorphous nanomaterials offer potential advantages in overcoming these limitations due to their unique structural properties. They are characterised by a non-crystalline, disordered atomic structure and are similar to a solidified liquid at the nanoscale. Among the amorphous nanomaterials used in dentistry, there are five major categories: calcium-, silicon-, magnesium-, zirconia-, and polymer-based systems. This study reviewed these amorphous nanomaterials by investigating their synthesis, properties, applications, limitations, and future directions in dentistry. These amorphous nanomaterials are synthesised primarily through low-temperature methods, including sol–gel processes, rapid precipitation, and electrochemical etching, which prevent atomic arrangements into crystalline structures. The resulting disordered atomic configuration confers exceptional properties, including enhanced solubility, superior drug-loading capacity, high surface reactivity, and controlled biodegradability. These characteristics enable diverse dental applications. Calcium-based amorphous nanomaterials, particularly amorphous calcium phosphate, demonstrate the ability to remineralise tooth enamel. Silicon-based amorphous nanomaterials function as carriers that can release antibacterial agents in response to stimuli. Magnesium-based amorphous nanomaterials are antibacterial and support natural bone regeneration. Zirconia-based amorphous nanomaterials strengthen the mechanical properties of restorative materials. Polymer-based amorphous nanomaterials enable controlled release of medications over extended periods. Despite the advances in these amorphous nanomaterials, there are limitations regarding material stability over time, precise control of degradation rates in the oral environment, and the development of reliable large-scale manufacturing processes. Researchers are creating smart materials that respond to specific oral conditions and developing hybrid systems that combine the strengths of different nanomaterials. In summary, amorphous nanomaterials hold great promise for advancing dental treatments through their unique properties and versatile applications. Clinically, these materials could improve the durability, bioactivity, and targeted drug delivery in dental restorations and therapies, leading to better patient outcomes. Full article

Background and Objectives: Peripheral arterial disease (PAD), frequently observed in individuals with type 2 diabetes mellitus (T2DM), is associated with diminished life quality, increased cardiovascular risk, and higher mortality rates. Similarly, trimethylamine N-oxide (TMAO), a uremic toxin produced by gut microbiota, has been linked to hypertension, cardiovascular disease, and increased overall mortality. In this study, we aimed to investigate whether serum TMAO levels are related to PAD in T2DM cases. Materials and Methods: In this cross-sectional investigation performed at one medical center, 120 patients with type 2 diabetes mellitus (T2DM) were included. High-performance liquid chromatography–mass spectrometry and an automated oscillometric device were used to measure serum TMAO levels and ankle–brachial index (ABI) values, respectively. Individuals exhibiting an ABI of less than 0.9 were classified as belonging to the low-ABI group. Results: Of the 120 participants, 23 (19.2%) had low ABI. Compared with the normal-ABI group, the low-ABI group was older (p = 0.017) and exhibited higher levels of urine albumin-to-creatinine ratio (UACR, p < 0.001), C-reactive protein (CRP, p < 0.001), and TMAO (p < 0.001). After adjusting for age, UACR, and CRP, multivariable logistic regression analysis identified serum TMAO concentration as an independent predictor of PAD in T2DM patients (odds ratio [OR]: 1.051; 95% confidence interval [CI]: 1.017–1.086; p = 0.003). In Spearman’s rank correlation analyses, log-transformed left ABI (log-left ABI, p = 0.017) and log-right ABI (p = 0.001) negatively correlated with log-TMAO. In patients with T2DM, the predictive performance of serum TMAO levels for PAD yielded an area under the receiver operating characteristic (ROC) curve of 0.812 (95% CI: 0.701–0.923; p < 0.001). Conclusions: Among individuals with T2DM, higher serum TMAO levels were associated with lower left and right ABI values and an increased likelihood of PAD. Full article

Background/Objectives: Pregnancy represents a unique physiological state marked by extensive metabolic adaptations, particularly in lipid pathways essential for maternal adjustments, fetal development, and postpartum recovery. This study aimed to explore these changes through untargeted lipidomic profiling. Methods: This observational, comparative, non-interventional clinical study included 107 women, of which 65 were in the third trimester of pregnancy (mean age 27.9 ± 5 years) and 42 were in the early postpartum period (≤7 days, mean age 28.9 ± 5.9 years). Inclusion criteria were singleton, term pregnancies (37–41 weeks) with neonates weighing > 2500 g and no associated pregnancy-related pathologies; exclusion criteria included multiple gestation, use of lipid-altering medications, maternal age > 40 years, or diagnosed pregnancy complications. Plasma samples were analyzed using High-Performance Liquid Chromatography–Quadrupole Time-Of-Flight–Electrospray Ionization (positive mode)–Mass Spectrometry, data were processed with MetaboAnalyst 6.0 using multivariate and univariate analyses (Partial Least Squares–Discriminant Analysis, Volcano Plot, Random Forest, Receiver Operating Characteristic analysis), with statistical significance set at p < 0.05. Results: Multivariate analysis demonstrated a clear separation between groups with high predictive accuracy as reflected by strong classification metrics (Accuracy = 0.90, R² = 0.75, Q² = 0.68). Several discriminative lipids were consistently identified across statistical models, including 2-Methoxyestrone (AUC = 0.861), Eicosanedioic acid (AUC = 0.854), and Pregnenolone sulfate (AUC = 0.843). These biomarkers were further categorized into five major lipid classes: steroid hormones, long-chain fatty acids, lysophospholipids, ceramides/sphingolipids, and glycerolipids. Conclusions: Untargeted lipidomic profiling revealed distinct metabolic signatures that differentiate late pregnancy from early post-partum states. The identification of robust lipid biomarkers with high discriminative performance highlights their potential utility in maternal health monitoring, obstetric risk assessment, and postpartum recovery surveillance. Full article

The coagulation cascade triggered by the contact between blood and the surface of implantable/interventional devices can lead to thrombosis, severely compromising the long-term safety and efficacy of medical devices. As an alternative to systemic anticoagulants, surface anticoagulant modification technology can achieve safer hemocompatibility on the device surface, holding significant potential for clinical application. This article systematically elaborates on the latest research progress in the surface anticoagulant modification of blood-contacting materials. It analyzes and discusses the main strategies and their evolution, spanning from physically inert carbon-based coatings and heparin-based drug-functionalized surfaces to hydrophilic/hydrophobic dynamic physical barriers, biologically signaling regulatory coatings, and bio-integrative/regenerative endothelium-mimicking surfaces. The advantages and limitations of the respective methods are outlined, and the potential for synergistic application of multiple strategies is explored. A special emphasis is placed on current research hotspots regarding novel anticoagulant surface technologies, such as hydrogel coatings, liquid-infused surfaces, and 3D-printed endothelialization, aiming to provide insights and references for developing long-term, safe, and hemocompatible cardiovascular implantable devices. Full article

Egg products are a convenient and safe form of eggs, possessing valuable nutritional and functional properties. The egg processing industry is responsible for the enormous amounts of biomass in the form of animal by-products (ABPs). According to EU legislation, the ABPs are under strict control from the formation to the disposal of biomass, as they carry a risk to the ecosystem and public health. For this reason, restrictions have been introduced on their use after disposal, ranging from bioactive applications in medical, cosmetic, and pharmaceutical products, as well as feed. The shells are subject to special conditions for processing and use. The by-products of egg breaking are divided into solid (eggshells and eggshell membranes) and liquid (technical albumen) by-products. The biological value is determined by the composition, which varies significantly across the by-products. In the context of the circular economy, all egg by-products contain valuable substances that can be used in food and non-food industries. First, eggshells are the leading by-product, composing 95% of the inorganic substance calcium carbonate, which, after processing, can be used in agriculture, food and feed industries, and medicine. Second, there is a liquid by-product containing proteins from the egg white and a small part of fats from the yolk. Literature data on this by-product are scarce, but there is information about its use as a feed additive, while the extracted and purified proteins can be useful in pharmacy. Egg membranes constitute only 1% of the egg mass, but humanity has long known about the benefits of collagen, keratin, and glycosaminoglycans, including hyaluronic acid, which compose this material. The processed membranes can be used as a food additive, in cosmetics, medicine, or pharmacy, just like other egg by-products mentioned above. This literature review focuses on the possible methods and techniques for processing by-products and their potential application. The literature sources in this review have been selected according to their scientific and practical applicability. The utilization of these by-products not only reduces the impact on the environment but also facilitates the creation of value-added materials. Full article

Isosorbide-based aliphatic polyesters are a promising class of biodegradable polymers for biomedical applications, representing an attractive alternative to poly(α-hydroxy acids). Derived from the bio-based bicyclic diol, they combine structural rigidity, tunable hydrophilicity, and enhanced biocompatibility, making them suitable for drug delivery and sustainable medical devices. In this study, we developed novel in situ forming implant (ISFI) formulations composed of poly(isosorbide sebacate) (PISEB) and dimethyl isosorbide (DMI), and evaluated their applicability for local delivery of doxycycline hyclate (DOXY), minocycline hydrochloride (MIN), and/or eugenol (EUG). Basic characteristics of new ISFI formulations were investigated. Rheological analysis demonstrated that the liquid formulations exhibited shear-thinning behavior, which is advantageous for ISFI systems. However, the MIN-loaded formulation exhibited excessively rapid drug release, with a pronounced initial burst (86.4 ± 5.9%) within 24 h, whereas the DOXY-loaded system showed a lower burst of 41.1 ± 5.9% over the same period. The effect of EUG addition on depot morphology and antibiotic release profiles was also assessed. In vitro drug release studies demonstrated that EUG reduced the release rate of both antibiotics, increasing and prolonging their antibacterial activity. Eugenol co-released with antibiotics also reduced the pro-inflammatory effect of the released antibiotic doses by more than tenfold. Full article

Objectives: This study aimed to evaluate the experience and consequences of dental caries and erosion in children aged 1–14 years on long-term liquid medications compared to those not on these medications. Methods: A cross-sectional observational study was conducted using a WHO-adapted questionnaire, medical surveys, and oral examinations. Participants included children with nephrotic syndrome in two groups: those on long-term liquid medications for at least three months (study group) and those not taking liquid medications (control group). The Decayed, Missing, and Filled Surfaces index (dmfs/DMFS) assessed caries, while the Pulpal Involvement, Ulceration, Fistula, and Abscess index (PUFA/pufa) measured caries consequences. The Basic Erosive Wear Examination index (BEWE) assessed erosion. Results: A total of 64 participants were included, with 33 in the study group and 31 in the control group. The study group had a significantly higher mean dmfs/DMFS of 16.9 ± 12.6 versus 5.2 ± 4.0 in the control group (p < 0.001). The PUFA/pufa index was also higher in the study group (0.8) compared to the control group (0.1) (p = 0.009). Erosion showed a non-significant increase with a BEWE score of 0.2 vs. 0.03 in the control group (p = 0.053). Conclusions: Long-term liquid medication use significantly affects dental caries in children after three months. Full article

Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis and complex diagnostic pathways. Pulmonologists often play a central role in its initial recognition and investigation. This narrative review synthesizes the current evidence on the diagnostic approach to MPM, with emphasis on imaging, tissue sampling, histopathology, and emerging diagnostic innovations relevant to clinical pulmonology. Methods: English-language studies published between January 2005 and June 2025 were identified from PubMed and Scopus. International guidelines and consensus documents were also reviewed to provide an updated overview of diagnostic strategies. Results: Diagnosis of MPM relies on a stepwise integration of clinical, radiological, and pathological information. Thoracic ultrasound, computed tomography, positron emission computed tomography and magnetic resonance imaging complement each other across different stages of the diagnostic pathway. Image-guided pleural biopsy and medical thoracoscopy remain the gold standard for tissue confirmation, supported by immunohistochemistry and molecular testing. The 2021 World Health Organization classification of pleural tumors and the International Association Study of Lung Cancer 9th Edition Tumour-Node-Mestastatis system have refined histologic and staging criteria, thereby improving reproducibility and prognostic accuracy. Emerging tools, including liquid biopsy, novel serum and molecular biomarkers, artificial-intelligence-based radiomics, and breathomics, offer promise for earlier and less invasive diagnosis but require prospective validation. Conclusions: Current advances are redefining MPM diagnosis toward integrated, multidisciplinary, and precision-based models. Future priorities include standardizing diagnostic algorithms, validating minimally invasive biomarkers, and integrating AI and molecular profiling into clinical workflows to enhance patient stratification. Full article

Arteriovenous malformations (AVMs) are fast-flow vascular malformations formed by direct artery-to-vein shunts without an intervening capillary bed, which increases the risk of hemorrhage and organ-specific damage. A synthesis of recent advances shows that AVMs arise from interplay between germline susceptibility (ENG, ACVRL1, SMAD4, RASA1, EPHB4), somatic mosaicism (KRAS, MAP2K1, PIK3CA), perturbed signaling (TGF-β/BMP, Notch, VEGF, PI3K/AKT, RAS/MAPK), hemodynamic stress, and inflammation. Multimodal imaging—digital subtraction angiography (DSA), MRI/MRA with perfusion and susceptibility sequences, CTA, Doppler ultrasound, and 3D rotational angiography—underpins diagnosis and risk stratification, while arterial spin labeling and 4D flow techniques refine hemodynamic assessment. Management is individualized and multidisciplinary, combining endovascular embolization, microsurgical resection, and stereotactic radiosurgery (SRS); a non-surgical approach and monitoring remain reasonable for some asymptomatic AVMs. Device and technique innovations (detachable-tip microcatheters, pressure-cooker approaches, and newer liquid embolics such as PHIL and Squid) have broadened candidacy, and precision-medicine strategies, including pathway-targeted pharmacotherapy, are emerging for syndromic and somatic-mutation–driven AVMs. Animal models and computational/radiomics tools increasingly guide hypothesis generation and treatment selection. We outline practical updates and future priorities: integrated genomic-imaging risk scores, genotype-informed medical therapy, rational hybrid sequencing, and long-term outcome standards focused on hemorrhage prevention and quality of life. Full article