Search Results (746)

Hepatoblastoma (HB), the most common pediatric liver malignancy, tends to be highly curable although advanced or recurrent disease has less favorable outcomes. Because patients are invariably <3–4 years of age, chemotherapies can cause significant long-term morbidities. Immortalized HB cell lines could be of great utility for drug screening, for the identification of novel therapeutic susceptibilities, and for studies requiring highly regulated and/or rapidly changing in vitro environments. However, HB research is hampered by a paucity of these lines that could be used for such purposes, with only two human cell lines being readily available, neither of which represents the most common HB molecular subtypes. Recently, immortalized cell lines have been derived from murine HBs that are driven by the most common oncogenes and tumor suppressors associated with human tumors. These comprise five distinct groups associated with the deregulation of each of the four possible combinations of oncogenic forms of the β-catenin, YAP and NRF2 transcription factors or the over-expression of MYC. All five groups share many of the attributes and molecular signatures of actual human HBs. In addition, they have been used for purposes as diverse as identifying novel molecular targets through the use of Crispr-based screens and the demonstration that some HB cells can trans-differentiate into endothelial cells that facilitate tumor growth. The experience gained from these models and advances in the propagation of human hepatocytes in mice suggests that it may soon be possible to generate bespoke human immortalized human cell lines. Full article

Background/Objectives: Epithelial ovarian cancer (EOC) encompasses ovarian, fallopian tube and peritoneal malignancies. It is a deadly disease and is rarely cured when diagnosed at advanced stages. Early-stage disease is often curable, but clinicians and researchers have been stymied in their attempts to reliably screen for this disease, even in high-risk populations. Effective prevention of ovarian cancer is usually limited to the use of combined oral contraceptives and removal of the ovaries and fallopian tubes. Methods and Results: We aim to review the current guidelines and the evidence reported for both the early detection and prevention of ovarian cancer. Novel imaging techniques, biomarkers, and surgical advances will be discussed. Conclusions: This review will offer (a) an understanding of the epidemiology of EOC (b) analysis and a discussion of relevant molecular markers that might be exploited for more accurate early detection (c) medical and surgical methods to prevent ovarian cancer. Full article

Vital pulp therapy (VPT) seeks to preserve pulp vitality by using biocompatible with regenerative potential. This study tested the hypothesis that an injectable gelatin methacryloyl (GelMA) hydrogel containing piezoelectric barium titanate promotes odontogenic differentiation of dental pulp stem cells (DPSC) significantly better than a commercially available tricalcium silicate material used for vital pulp therapy. First, the light-curable, injectable piezoelectric hydrogel was engineered and characterized for its physicomechanical, piezoelectric properties and biocompatibility to DPSCs. The effect of this gel on the odontogenic differentiation of DPSCs was determined by measuring the expression level of key genes, compared to Biodentine XP. The hydrogel exhibited excellent injectability (<1 kgf of force), mechanical stability, and generated physiologically relevant voltages under cyclic loading mimicking mastication. MTT and ROS assays show no cytotoxic or damaging oxidative stress effects. When DPSCs were cultured over the materials under cyclic loading, the piezoelectric hydrogel significantly enhanced cell viability and upregulated COL1A1, DSPP, and DMP1 expression compared to Biodentine XP and non-piezoelectric hydrogel controls. These findings establish piezoelectric hydrogel as a self-powered, bioactive platform that converts physiological forces into regenerative bioelectric cues, offering a promising next-generation material for vital pulp therapy. Full article

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery. Full article

This article presents the results of research on UV-curable epoxy coatings developed with selected plant modifiers such as garlic (Allium sativum), turmeric (Curcuma longa), common nettle (Urtica dioica), and privet (Ligustrum vulgare). This study aimed to evaluate the influence of these natural components on the functional properties of UV-cured coatings and to assess their potential as bio-based modifiers. The coatings were formulated using Epidian^® 5 epoxy resin, a safe and non-toxic material approved for food-contact applications, and cured with a commercial cationic photoinitiator. Their mechanical, surface, optical, and antibacterial properties were investigated. The results showed that all plant-based additives modified both the mechanical and esthetic characteristics of the coatings; however, garlic demonstrated outstanding antibacterial activity, achieving nearly complete inhibition of Staphylococcus aureus growth with a reduction rate of 99.998%. These findings highlight that natural modifiers, especially garlic, can serve as highly effective functional components, while future work should focus on implementing these coatings for surfaces exposed to bacteria, such as public utility items and shop, hospital, sports, and rehabilitation equipment. Full article

Acute promyelocytic leukemia (APL) evolved from the most lethal to the most curable subtype of acute leukemia today, owing to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide. Despite cure rates exceeding 90% and the rarity of relapse or refractoriness, early death (ED)—occurring within 30 days of diagnosis—remains unacceptably high, reaching up to 30% in population-based studies. ED is the major barrier to universal cure, with fatal hemorrhage as the predominant cause, followed by infection, differentiation syndrome, and thrombosis. Patients who survive the initial month generally achieve excellent long-term outcomes. This review synthesizes data from clinical trials and large real-world cohorts to provide a comprehensive overview of the incidence, causes, and predictors of ED in APL. Higher white blood cell count and older age emerge as the most consistently validated predictors, followed by increased IRB/BICcreatinine, low albumin, thrombocytopenia, and coagulopathy, although their predictive value is not uniform across studies. Risk scores such as the Sanz classification, the Österroos ED model, and dynamic disseminated intravascular coagulation (DIC) assessments represent practical tools for identifying patients at high risk of ED. Importantly, ED rates remain significantly higher in real-world populations than in clinical trials, highlighting the impact of age and comorbidities, delayed diagnosis, and barriers to immediate ATRA initiation and supportive care. Addressing ED in APL requires intensified early supportive strategies, physician awareness and education, and rapid treatment initiation. Refinement and validation of predictive models may guide tailored interventions and inform strategies to finally overcome this persistent unmet need. Full article

Silica-based splitters, couplers, and arrayed waveguide gratings are key components in optical communication. However, the high tuning power consumption of silica chips limits their development and application in fields such as Reconfigurable Optical Add/Drop Multiplexers and Mode Division Multiplexing. In this work, we demonstrate a silica thermo-optic switch based on polymer cladding within a Mach–Zehnder Interferometer framework, in which a UV-curable polymer is employed as the upper cladding to enhance thermal efficiency. The device exhibits a power consumption of 48 mW, rise and fall response times were 215 µs and 271 µs, compared to all-silicon switches, the power consumption is reduced by 75%, and the switching speed is improved by nearly a factor of two, while maintaining a comparable insertion loss. Experimental results demonstrate an insertion loss of 8.53 dB and an extinction ratio of 10.12 dB. Full article

Background/Objectives: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the t(15;17)(q24;q21) translocation, generating the PML::RARA fusion gene that blocks myeloid differentiation and drives leukemogenesis. Despite advances in therapy, early mortality remains a major challenge due to severe coagulopathy. This review aims to summarize recent insights into APL pathophysiology, diagnostic approaches, and management strategies. Methods: We performed a comprehensive review of the literature addressing the molecular mechanisms of APL, its associated coagulopathy, and current diagnostic and therapeutic standards, with a focus on evidence-based recommendations for clinical practice. Results: The hallmark PML: RARA oncoprotein disrupts nuclear body function and retinoic acid signaling, resulting in differentiation arrest and apoptosis resistance. APL-associated coagulopathy arises from overexpression of tissue factor, release of cancer procoagulant, inflammatory cytokines, and annexin II-mediated hyperfibrinolysis. Diagnosis requires integration of cytomorphology, immunophenotyping, coagulation studies, and molecular confirmation. Immediate initiation of all-trans-retinoic acid (ATRA) upon clinical suspicion, combined with aggressive supportive care, is critical to control bleeding risk. Conclusions: APL is now a highly curable leukemia when recognized early and treated with targeted therapy. Rapid diagnosis, prompt ATRA administration, and meticulous hemostatic support are essential to reduce early mortality. Further refinements in minimal residual disease monitoring are expected to improve patient outcomes. Full article

Background and Clinical Significance: Warty (condylomatous) squamous cell carcinoma (SCC) of the uterine cervix is a rare papillary variant of SCC, usually associated with good prognosis. Case Presentation: We report the clinical case of a postmenopausal woman with vaginal bleeding, anemia, and an enlarged, exophytic tumor mass protruding from the cervix. MRI showed a solid–necrotic cervical–uterine mass with invasion of bladder, rectum, both parametria, and the left ureter, with regional lymphadenopathy and FIGO IVA stage was established. Biopsies from the cervical tumor revealed invasive, well-differentiated SCC with conspicuous koilocytic atypia in superficial and deep nests, consistent with warty (condylomatous) SCC. Immunohistochemistry showed p16 overexpression, an intermediate nuclear proliferation rate, and a non-mutational pattern for p53 immunostaining. Radiotherapy was recommended but the patient’s condition deteriorated rapidly and she died three months after initial diagnosis. Due to the rarity of this type of tumor, we conducted a search on PubMed, Scopus, and Web of Science from inception to 31 July 2025 and we identified ten reports available for evaluation. A total of 32 cases were identified, usually with FIGO stage I or II, mostly with low-risk HPV infection and with good prognosis. Conclusions: The advanced stage and limited tolerance for therapy in this case emphasize the importance of HPV vaccination and HPV-based screening to prevent late, non-curable presentations. Accurate distinction from condyloma acuminatum and verrucous or papillary SCC is clinically relevant because management and outcomes differ. Since some of the cases reported in the literature had a worse clinical course, with shorter disease-free survival and overall survival, including our case, further research is mandatory in the future to unravel those features which might predict a poor outcome. Full article

Homeostasis, which supports and maintains brain function, results from the continuous regulation of thermodynamics within tissue: the balance of heat production, redox oscillations, and vascular convection regulates coherent energy flow within the organ. Neuroinflammation disturbs this balance, creating measurable entropy gradients that precede structural damage to its tissue components. This paper proposes that a thermodynamic unity can be devised that incorporates nanoscale physics, energetic neurophysiology, and systems neuroscience, and can be used to understand and treat neuroinflammatory processes. Using multifactorial modalities such as quantum thermometry, nanoscale calorimetry, and redox oscillometry we define how local entropy production (s_t), relaxation time (τ^R), and coherence lengths (λc) allow quantification of the progressive loss of energetic symmetry within neural tissues. It is these variables that provide the basis for the etiology of thermodynamic biomarkers which on a molecular-redox-to-network scale characterize the transitions governing the onset of the neuroinflammatory process as well as the recovery potential of the organism. The entropic probing of systems (PEP) further allows the translation of these parameters into dynamic patient-specific trajectories that model the behavior of individuals by predicting recurrent bouts of instability through the application of machine learning algorithms to the vectors of entropy flux. The parallel development of the nanothermodynamic intervention, which includes thermoplasmonic heat rebalancing, catalytic redox nanoreacting systems, and adaptive field-oscillation synchronicity, shows by example how the corrections that can be applied to the entropy balance of the cell and system as a whole offer a feasible form of restoration of energy coherence. Such closed loop therapy would not function by the suppression of inflammatory signaling, but rather by the re-establishment of reversible energy relations between mitochondrial, glial, and vascular territories. The combination of these factors allows for correction of neuroinflammation, which can now be viewed from a fresh perspective as a dynamic phase disorder that is diagnosable, predictable, and curable through the physics of coherence rather than the molecular suppression of inflammatory signaling. The significance of this set of ideas is considerable as it introduces a feasible and verifiable structure to what must ultimately become the basis of a new branch of science: predictive energetic medicine. It is anticipated that entropy, as a measurable and modifiable variable in therapeutic “inscription”, will be found to be one of the most significant parameters determining the neurorestoration potential in future medical science. Full article

Syphilis, a curable sexually transmitted infection, has resurged globally, challenging public health systems in both high-income countries and low- and middle-income countries (LMICs). In nations like the United States, the United Kingdom, parts of Europe, Canada, and Japan, cases have surged due to declining condom use, digital platforms facilitating casual sex, and practices like chemsex and broader drug use for sex, with rising congenital syphilis rates. In LMICs, such as those in East Africa, South Asia, Latin America, and Southeast Asia, limited healthcare access, inadequate prenatal screening, and socioeconomic barriers drive persistent high prevalence, particularly among pregnant women and vulnerable populations. Despite contextual differences, shared drivers include stigma, health disparities, and outdated surveillance systems. This resurgence underscores the need for globally coordinated, equity-focused strategies, including universal syphilis testing, modernized surveillance, and context-specific sexual health education. Addressing structural and behavioral factors through collaborative international efforts is critical to reversing this trend and strengthening global STI control. Full article

Endometrial cancer (EC) is the most common gynecologic cancer. Early detection is one of the most important predictors of survival. The cancer is curable if detected early but the five-year survival rate in advanced cases can be as low as 22%. Microsatellite instability (MSI) testing is used to screen populations for Lynch Syndrome (LS), the most common cause of inherited EC, and to classify EC into distinct groups with unique histological, prognostic, and molecular features. Accurate sample identification is crucial for successful MSI testing because instability is assessed by comparing amplification patterns in markers in the normal and tumor samples that must be taken from the same individual. Penta-C and Penta-D pentanucleotide markers are used widely for sample identification in not only MSI testing but also parentage verification, forensic science, and population genetics studies. The objective of this study was to test 324 pairs of tumor and matched normal DNAs from EC patients for instability in these markers using the Promega MSI Analysis System^TM considered the “gold standard” in MSI testing. Both markers were unstable, and therefore not reliable for MSI testing, in 8.2% of the EC patients with MSI. Instability in both mono- and pentanucleotide markers suggest that the tumors with MSI likely suffer from a “generalized” form of instability also affecting other short tandem repeats. Results from many studies using these markers for various purposes may not be accurate if samples with MSI are involved. Full article

Antimicrobial resistance (AMR) is a present, pressing global public health crisis associated with rising morbidity and mortality rates due to previously curable infectious disease. Targeted drug delivery is an important approach to address AMR due to its ability to improve the therapeutic performance of antibiotics without leading to any adverse effects or organ toxicities. In this review we explore molecular mechanisms of AMR and drawbacks of conventional antibiotic therapies and discuss unique drug delivery approaches to compensate these. Nanoparticulate carrier systems, stimuli-responsive systems, antibody–drug conjugates, and CRISPR-Cas systems are some of the carrier method designs that are promising for tackling hard to treat infections related to pathogenic strains and biofilms due to their features. Many of these are among the most significant advances in the field. However, there are many challenges to be overcome, with biological limitations, scaling and regulatory challenges, etc., before they can be employed in commercial applications. Materials are being developed, and an approach standardized and applicable to future work is in development to improve the efficiency of targeted delivery systems. Controlled drug delivery, which could be the answer to an increasing AMR problem, will not only help in alerting awareness among individuals but will also help in prolonging the activity of antibiotics by providing synergistic interdisciplinary solutions. This review emphasizes the complementary role of targeted drug delivery in transitioning from laboratory investigations to clinical therapy. It addresses underrepresented aspects, including new materials, scalability, regulatory considerations, and ethical implications, while offering a roadmap for translating innovations into next-generation antimicrobials. Full article

Background: Three-dimensional (3D) printed scaffolds have emerged as promising tools for bone regeneration, but the optimal structural design and pore size remain unclear. Polylactic acid (PLA) reinforced with graphene oxide (GO) offers enhanced mechanical and biological performance, yet systematic evaluation of architecture and pore size is limited. Methods: Two scaffold architectures (lattice-type and dode-type) with multiple pore sizes were fabricated using UV-curable PLA/GO resin. Physical accuracy, porosity, and mechanical properties were assessed through compression and fatigue testing. Based on in vitro screening, four pore sizes (930 μm, 690 μm, 558 μm, 562 μm) within the dode-type structure were analyzed. The 558 μm and 562 μm scaffolds, showing distinct fracture thresholds, were further evaluated in rat and rabbit calvarial defect models for inflammation and bone regeneration. Results: In vitro testing revealed that while 930 μm and 690 μm scaffolds exhibited superior compressive strength, the 562 μm scaffold showed a unique critical fracture behavior, and the 558 μm scaffold offered comparable stability with higher resistance to premature failure. In vivo studies confirmed excellent biocompatibility in both groups, with early bone formation favored in the 558 μm scaffold and more continuous and mature bone observed in the 562 μm scaffold at later stages. Conclusions: This stepwise strategy—from structural design to pore size screening and preclinical validation—demonstrates that threshold-level mechanical properties can influence osteogenesis. PLA/GO scaffolds optimized at 558 μm and 562 μm provide a translationally relevant balance between mechanical stability and biological performance for bone tissue engineering. Full article

Background: Symptom burden and functional impairment are common in women with breast cancer, yet their prevalence and clinical significance across the disease spectrum remain underexplored. We sought to describe symptom burden and performance status using patient-reported outcome measures and to identify patient characteristics associated with symptoms requiring clinical intervention. Methods: In this cross-sectional study, women with stage I–IV breast cancer completed the Edmonton Symptom Assessment System (ESAS) and the Patient-Reported Functional Status tool. We assessed the prevalence and severity of symptoms and calculated summary distress scores. Multivariable logistic regression was used to identify patient characteristics associated with clinically significant symptoms (ESAS ≥ 4). Results: Among 381 women (mean age 56.8 years; 27% metastatic; 72% with no comorbidities), 70% reported at least one moderate to severe symptom. The most common were tiredness (31%), lack of well-being (30%), and anxiety (21%). Mean summary distress scores were low overall. Most patients reported functional status scores of 0 or 1, and 43% of those with scores ≥2 had metastatic disease. Compared with metastatic patients, women within the first year after diagnosis were less likely to report a symptom requiring intervention (OR 0.49, 95% CI 0.24–0.90). Conclusions: Clinically significant symptoms are common among women with breast cancer, including those with potentially curable disease. Threshold-based use of ESAS, rather than reliance on mean scores, provides a more accurate assessment of patient needs. These findings support the routine integration of patient-reported outcomes into oncology care and underscore the importance of targeted multidisciplinary interventions. Full article