Search Results (30,082)

Trimodality therapy (TMT)—maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy—can offer oncologic outcomes comparable to radical cystectomy (RC) in carefully selected muscle-invasive bladder cancer (MIBC) patients while preserving the bladder and, possibly, the quality of life. Systematic reviews and long-term series support durable bladder-intact survival in responders, yet there is still a significant percentage of patients who exhibit incomplete response or invasive intravesical recurrence requiring salvage RC. This review covers computational genomics, transcriptomics, immune contexture, radiogenomics, and digital pathology approaches for predicting response in order to avoid preventable TMT failures. We discuss clinically relevant endpoints (complete response, invasive recurrence, bladder-intact survival, and salvage RC), patient selection (carcinoma in situ, hydronephrosis, debulking feasibility, and histology), and DNA damage response (DDR) biology—highlighting ERCC2 and related pathways as determinants of chemo-radiation sensitivity. We then review reproducible transcriptomic subtype classifiers and immune deconvolution methods, emphasizing translational constraints and reporting standards. Finally, we propose an integrated hypothetical modeling framework (calibration, external validation, and decision-curve thresholds) to guide recommendations for upfront RC versus bladder preservation with intensified surveillance and timely salvage RC. Full article

This Special Issue (SI) was intended to gather high-quality original research articles and reviews on the above topic, with an emphasis on the essential role of VLF (very low frequency, 3–30 kHz)/ELF (extremely low frequency, 1 Hz–3 kHz) wave phenomena in a wide range of scientific fields from astrophysics, space physics, ionospheric physics, atmospheric electricity, and seismo-electromagnetics [...] Full article

Viral carcinogenesis as a causative mechanism of breast cancer has been intensively researched during the last decades. The role of Epstein–Barr virus (EBV) and Bovine Leukemia virus (BLV) in breast oncogenesis has been investigated in a plethora of studies, but with conflicting results. The aim of this systematic review and meta-analysis was to compare the frequency of molecular detection of the EBV genome and BLV genome between women with breast cancer and women without malignant breast tumors. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to 20 May 2024. Included studies were those comparing the frequency of molecular detection of the EBV and/or BLV genome in breast tissue specimens with polymerase chain reaction (PCR) methods between patients with breast cancer and women without breast malignancies. The primary outcomes of the study were the frequency of molecular detection of the EBV genome and BLV genome. Methodological quality of included studies was assessed using the Newcastle–Ottawa Scale. A total of 29 studies met the selection criteria and were included in this meta-analysis; 19 studies reported results for molecular detection of the EBV genome, 9 studies for detection of the BLV genome and 1 study for detection of genomic material of both viruses. The frequency of molecular detection of viral genomes was significantly higher in patients with breast cancer, compared to women with healthy breasts or benign breast diseases, regarding both EBV (OR: 3.041, 95% CI: 1.791 to 5.164, p < 0.0001) and BLV (OR: 3.459, 95% CI: 2.118 to 5.650, p < 0.0001). The frequency of molecular detection of EBV and BLV genomes is higher, in a statistically significant manner, in patients with breast cancer compared to women without breast malignancies. The presence of these viral factors in breast tissue could imply their potential contribution in breast carcinogenesis, but is not sufficient to establish it, and the molecular detection of their genomes could be potentially exploited in the future for preventive, diagnostic and therapeutic purposes. Further studies are required to thoroughly investigate and establish a causal relationship between EBV and BLV infection and breast carcinogenesis, as well as to support the use of viral genome molecular detection in clinical settings for the management of breast cancer patients. Full article

Background/Objectives: Blood transfusion is a crucial component in the treatment of individuals with sickle cell disease [SCD]; nonetheless, multiple transfusions can lead to considerable complications, notably alloimmunization. However, the prevalence of alloimmunization and its predictors remain incompletely explained. This review aimed to determine its global prevalence and identify associated risk factors. Method: Our protocol was registered in PROSPERO [ID: CRD420251167042] in accordance with the PRISMA 2020 criteria. A thorough literature search was conducted across PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to identify studies reporting the prevalence of alloimmunization in adults with confirmed sickle cell disease who have received blood transfusions. This search included all publications up to 16 April 2026. Two reviewers independently screened and extracted data, and the Newcastle–Ottawa Scale was used to evaluate the study’s quality. After the Freeman–Tukey transformation, a random-effects model was used to estimate the pooled prevalence. We examined disparities among groups and geographies, study designs, and matching procedures to determine their differences. We additionally employed meta-regression to identify potential predictors. Results: Nine studies [n = 1711; 1978–2026] met the inclusion criteria. The overall rate of alloimmunization was 28.9% [95% CI 22.4–35.4; I² = 88.5%]. The most prevalent antibodies were those of the Rh and Kell systems, with anti-E antibodies being the most frequent, followed by anti-C and anti-K antibodies. A higher number of transfusions and the HbSβ⁰ genotype were both persistent risk factors, while older age at first transfusion appeared protective. Extended antigen matching dramatically reduced prevalence, though approximately 9% of individuals remained affected. Conclusions: Alloimmunization continues to challenge transfusion management in adults with SCD. Broader implementation of extended antigen matching and genotype-informed transfusion strategies may help mitigate this risk. Full article

Cyberworthiness extends the concept of cybersecurity by evaluating whether systems and networks can perform their intended functions securely while maintaining protection against cyber threats. In corporate environments, cyberworthiness aims to ensure security, operational resilience, and trustworthiness across interconnected business processes and digital infrastructures. Modern organisations increasingly rely on complex cyber–physical and information systems, where vulnerabilities in software, networks, and devices can introduce significant operational and security risks. Cyberworthiness, therefore, encompasses security controls, risk management practices, and compliance with recognised cybersecurity standards and governance frameworks. It supports the assessment of information technology components and their exposure to both known and emerging cyber attacks, enabling organisations to evaluate system robustness and operational continuity. While cyberworthiness has historical foundations in system assurance and dependability, it also provides a conceptual basis for contemporary cyber resilience strategies. This paper discusses the concept of cyberworthiness in corporate organisations and identifies potential pathways for its practical implementation. It analyses existing cybersecurity standards and governance frameworks to support structured cyberworthiness assessment. This study presents a structured comparative review of fifteen cyberworthiness-relevant standards, supported by a Source Quality Appraisal Framework, a Framework Selection Guide specifying when each standard should be preferred and where conflicts arise, and a five-dimensional Cyberworthiness Assessment Readiness Model (CARM), a directional self-assessment instrument. The Efficient Automatic Safety and Security Assurance (EASSA) concept is proposed as a direction for future research, not a validated deployed system. Ensuring cyberworthiness remains challenging due to automation limitations in all reviewed standards, evolving threat landscapes, and governance complexity, requiring organisations to adopt integrated and measurable approaches to safeguard their digital assets and operational systems. Full article

Against the global backdrop of carbon neutrality and the green transition of the construction sector, modern timber-framed buildings have emerged as a core enabler of sustainable construction. However, a systematic synthesis of research on indoor hygrothermal environments and thermal comfort in such buildings remains lacking, and the underlying coupling mechanisms—as well as pathways for performance optimization—are still insufficiently understood. To address these gaps, this study aims to systematically characterize and evaluate the performance features of indoor thermal and moisture environments in modern timber buildings, and to identify the key influencing factors and their underlying mechanisms. In accordance with the PRISMA 2020 guidelines for systematic reviews, this study identified and analyzed 203 high-quality peer-reviewed publications retrieved from three major academic databases, covering the period 2010–2025. Specifically, the literature search was conducted across the Web of Science, Scopus, and the China National Knowledge Infrastructure (CNKI), and visualization analysis was performed using VOSviewer 1.6.20 software. The results indicate that timber-framed buildings exhibit distinctive indoor hygrothermal characteristics: rapid temperature response, strong humidity buffering capacity, and superior thermal insulation performance compared with concrete structures, enabling indoor relative humidity to remain stably within the thermally comfortable range. Nevertheless, challenges persist, including summer overheating and elevated risks of mold growth under hot-humid conditions. Furthermore, the PMV model demonstrates significant predictive deviation for thermal comfort in timber-framed buildings; its application thus requires calibration incorporating both the hygrothermal properties of timber materials and occupants’ psychological adaptation. This study synthesizes the current state of research, identifies key influencing factors, and proposes climate-responsive optimization strategies to advance the development of robust thermal comfort models and support the low-energy, high-comfort design of timber-framed buildings. Full article

Extremity vascular malformations in children and adolescents are congenital vascular developmental abnormalities that often present to pediatric orthopedic surgeons with pain, swelling, restricted motion, contracture, gait disturbance, limb asymmetry, and growth-related deformity rather than with an obvious vascular phenotype. The orthopedic importance of these lesions lies less in surface appearance than in their potential to affect muscle balance, joint integrity, osseous development, and peri-procedural safety. This review translates contemporary vascular anomaly classification and multidisciplinary management pathways into a practical orthopedic framework for diagnosis, referral, and longitudinal limb management. The most useful first step is to distinguish low-flow from high-flow lesions and then define lesion depth, periarticular or osseous involvement, coagulopathy risk, and syndromic overgrowth phenotype. Ultrasound is usually the first-line imaging modality for flow characterization, whereas magnetic resonance imaging is the cornerstone for defining extent and planning treatment. Plain radiographs remain highly relevant for identifying phleboliths, osseous remodeling, arthropathy, contracture-related deformity, and limb-length discrepancy. Venous malformations generally warrant pathway-based coagulation assessment, especially D-dimer and fibrinogen, because localized intravascular coagulopathy has direct implications for intervention and surgery. Arteriovenous malformations are best managed within specialist multidisciplinary teams. Fibro-adipose vascular anomaly and syndromic overgrowth phenotypes warrant particular attention because they frequently drive pain, contracture, and progressive limb imbalance. Outcome assessment in this field should extend beyond lesion size and incorporate pain, function, quality of life, and growth-related consequences. For pediatric orthopedic surgeons, management should move from late deformity correction toward early classification, early referral, longitudinal surveillance of joint and growth-related complications, and careful integration of local, surgical, and systemic therapies. Full article

Chronic pancreatitis (CP) is a fibro-inflammatory condition defined by permanent anatomical changes in the pancreas. The causes of CP are described by the TIGAR-O classification system: toxin-related, idiopathic, genetic mutations, autoimmune disorders, episodes of recurrent acute pancreatitis, and obstructions. Pain is multifactorial in nature, and common psychopathological consequences of CP, including depression and anxiety, complicate the clinical picture of chronic pancreatitis. As a result, the quality of life of patients with CP is decreased. This review describes the pathophysiology of pain and its relationship to underlying psychological consequences, with a focus on a long-term, holistic management approach. Strategies that combine physical and psychological management align with SDG 3 (Good Health and Well-being). CP predominantly affects patients from low socioeconomic backgrounds due to disparities in medical care, underscoring the relevance of achieving SDG 10 (Reduced Inequalities). This review emphasizes the importance of targeted research in developing a holistic care model for CP that aligns with the SDGs. Full article

Intravesical Bacillus Calmette–Guérin (BCG) is a recommended therapy approach for non-muscle invasive bladder cancer (NMIBC) to prevent disease progression and eliminate tumor cells. Nevertheless, some patients have shown resistance to BCG therapy, exhibiting disease recurrence and progression to MIBC, thereby necessitating radical cystectomy as the best-recommended treatment option. However, radical cystectomy greatly affects postoperative morbidity and quality of life, rendering many patients hesitant or surgically unsuitable for this invasive therapy. The concept of bladder preservation has emerged as an alternative, employing a diverse array of therapeutic agents and interventions to improve therapeutic efficacy to retain the bladder for as long as possible. In this review, we explore various established therapeutic agents and ongoing clinical trials involving new potential agents and interventions. This study was undertaken to determine the advantage of each agent and their combined therapeutic regimens in improving prognostic efficacy, offering an alternative to radical cystectomy for BCG-unresponsive NMIBC. Full article

Background: Peripheral muscle electrostimulation (PME), encompassing neuromuscular electrical stimulation (NMES) and functional electrical stimulation (FES), has been increasingly acknowledged as an effective adjunctive or complementary treatment to voluntary exercise in elderly cardiac patients who cannot perform sufficient amounts of exercise, for whom there is limited research on optimal protocols. Sarcopenia, defined as a progressive decrease in muscle mass, strength and function, affects approximately 34% of heart failure (HF) patients and considerably worsens their prognosis. The objective of this systematic review is to summarize current evidence on the theoretical mechanisms, physiological pathways, safety and efficacy of PME in older adults within a cardiac rehabilitation (CR) setting, with a specific emphasis on sarcopenia reversal. Methods: We performed a systematic review following the PRISMA 2020 guidelines. A systematic search was conducted on the PubMed, Embase, Cochrane Library, CINAHL and PEDro databases from inception until December 2025. We searched for randomized controlled trials (RCTs) and controlled clinical trials focusing on PME in patients with cardiac diseases aged 65 years or older. The main outcomes were physical function (assessed with the Short Physical Performance Battery [SPPB] and 6 min walk distance [6MWD]), muscle strength, muscle mass and safety. The Cochrane Risk of Bias tool was used to evaluate the quality of the studies. Results: Eight studies were included, with 387 participants and a mean age between 78 and 85 years. PME consistently improved lower-extremity muscle strength (MD: 5.2% body weight, 95% CI = 1.2–9.1, p = 0.013) along with SPPB scores, which ranged from +2.3 to +2.67 points (all p < 0.05). Home-based PME (NMES) achieved 100% adherence rates, and no cardiovascular adverse events were reported. The mechanisms by which PME is beneficial involve peripheral skeletal muscle adaptations without eliciting central hemodynamic stress, increased endothelial function, aerobic enzyme activity, protein anabolism stimulation or muscle proteolysis inhibition. No significant effects were observed on BNP levels, hospital readmissions or mortality. PME has been shown to attenuate the progression of sarcopenia through hypertrophy of type I and II muscle fibers, as well as mitochondrial biogenesis. Conclusions: PME is a safe, feasible adjunct to conventional CR in frail, elderly cardiac patients, particularly those with exercise intolerance and sarcopenia. It improves peripheral muscle function, physical performance, and muscle protein balance without cardiovascular stress. Larger multicenter trials are needed to establish optimal protocols and long-term clinical outcomes. Full article

Background: Chronic pain remains a primary driver of global disability and impaired quality of life. While digital conversational agents (CAs) have emerged as scalable tools for symptom monitoring and self-management via patient-reported outcome measures, their clinical efficacy remains poorly synthesized. This systematic review and meta-analysis aimed to evaluate the impact of CA-based interventions on PROMs in adults with chronic pain. Methods: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched from inception to 22 October 2025. Eligible studies were RCTs including adults with chronic pain and evaluating fully automated CA interventions, such as digital coaching or messaging programs. PROMs related to pain, well-being, disability, and work-related outcomes were extracted. Continuous outcomes were synthesized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Five RCTs involving 572 participants were included. Interventions were self-guided, digitally delivered, and lasted 4 to 12 weeks. The overall pooled analysis suggested a potential benefit of CA-based interventions on PROMs (SMD = −0.43; 95% CI −0.55 to −0.31; p < 0.00001), although heterogeneity and risk of bias across studies warrant cautious interpretation. Improvements were observed particularly in pain intensity, although evidence for other outcomes was less consistent, with some studies reporting benefits in quality of life, fear of movement, and well-being. Conclusions: CA-based interventions may have potential as adjuncts in chronic pain management; however, the current evidence is limited and should be interpreted with caution due to heterogeneity and risk of bias across studies. These tools may represent a scalable solution for supporting remote symptom monitoring and self-management within digital health frameworks, although further high-quality evidence is required. Full article

Bovine colostrum (COL) is widely used in dietary supplements, and previous studies have suggested its potential benefits for immune function, selected clinical conditions, wound healing, and athletic performance. This systematic review analyzed clinical trials published between 2001 and 2025 that investigated the effects of COL on human body fat and blood lipid profiles. The review was conducted in accordance with PRISMA guidelines, and study quality was assessed using Cochrane risk-of-bias tools. Thirteen studies were included. One study in older adults reported that COL supplementation at 60 g/day for 8 weeks significantly reduced body fat percentage by 0.4% (p < 0.05). Another study found that COL supplementation at 10 g/day combined with plant proteins for 12 weeks significantly attenuated the increase in leg tissue fat percentage compared with placebo (PLA) (0.48 ± 1.29% vs. 1.12 ± 1.27%, respectively; p < 0.05). Changes in blood lipid profiles were reported in two studies. In individuals with type 2 diabetes, COL supplementation at 10 g/day for 4 weeks significantly reduced total cholesterol (TC) and triglyceride levels in both men and women, by 8.27% vs. 7.62% and 11.96% vs. 21.46%, respectively. In another study involving older adults, COL supplementation at 30 g/day for 12 weeks significantly reduced TC (5.88 to 5.38 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (3.68 to 3.28 mmol/L) compared with PLA. Owing to substantial methodological heterogeneity and inconsistent findings, further randomized, double-blind trials are needed in larger groups of overweight or obese participants, with intervention periods lasting at least six months. Future studies should use a standardized COL dose of 20–25 g/day, controlled caloric deficits, and a four-arm design comparing placebo and COL under normocaloric and energy-restricted dietary conditions. Assessments should include blood metabolic biomarkers, body composition measured by dual-energy X-ray absorptiometry, gut microbiome composition, and fecal short-chain fatty acids to determine whether any observed benefits are attributable to COL alone or to its combination with dietary intervention. Full article

Introduction: A healthy diet is crucial for healthy growth and development during childhood and adolescence. Although evidence in this field is expanding rapidly, the focus has been on disease-oriented nutrition rather than on nutrition for healthy children and adolescents; thus, we aimed to identify key research gaps to guide future studies and policy development. Methods: For this scoping review, we systematically searched systematic reviews, clinical guidelines, and position papers. The literature search covered publications from the last eight years to provide the latest information on pediatric nutrition. A basic critical appraisal was performed to assess the quality of the evidence. Results: We included 14 studies. Six major topics were identified as the most frequently reported: healthy dietary patterns, sustainable dietary patterns, macronutrients and micronutrients, sugar intake, beverages and sugary drinks, and dairy products. Conclusions: Current information on healthy diets for children and adolescents focuses mainly on dietary patterns. However, regionalized information is lacking, as few health agencies report on specific dietary modifications, especially in developing or transition countries. Full article

High-fidelity simulations have become an important aid in clinical practice and research. In the pediatric field, they allow for the creation of scenarios involving emergency situations, in which decision-making algorithms must be rapidly applied, as is the case with airway management. Our narrative review examines articles in English indexed in PubMed, using the following search terms: high-fidelity simulation, pediatric, difficult airway management, bag mask ventilation, intubation, mechanical ventilation, tracheostomy, cricothyrotomy, laryngoscopy, fiberoptic bronchoscopy, and emergency situations. Airway management, along with venous access management, has always been one of the most challenging issues in pediatric anesthesia. The scarcity of patients and procedures, combined with the need to ensure high quality standards, necessitates simulations. Using high-performance devices and realistic settings allows us to reproduce not only the desired technical scenario, but also the emotions and group dynamics. High-fidelity simulations therefore prove to be an excellent aid for pediatric airway management, enhancing the hard and soft skills of both the team and the individual. Simulations allow us to replicate scenarios that are uncommon in clinical practice but have a significant impact due to their potential severity. Full article

Recycled aggregates (RAs) from construction and demolition waste (CDW) provide substantial circular-economy benefits, yet their elevated porosity, adhered mortar, and heterogeneity typically impair the mechanical performance and durability of recycled aggregate concrete (RAC). This PRISMA 2020-compliant systematic review synthesises 2180 records (2015–2026) to evaluate advanced strategies for enhancing RA quality prior to structural use. This paper critically compares removal-based treatments (mechanical, thermal, acid cleaning) with strengthening and densification approaches, including accelerated carbonation, pozzolanic and nano-silica coatings, polymer impregnation, microbial-induced calcium carbonate precipitation (MICP), and modified mixing methods such as triple-stage mixing (TSMA). Evidence shows that while all RA types (including recycled fine aggregate (RFA), recycled coarse aggregate (RCA), and their combination (RFCA)) can slightly reduce compressive strength and 30% replacement serves as a critical threshold, beyond this, strength loss accelerates, particularly in RCA and RFCA mixes. However, accelerated carbonation and TSMA consistently refine the interfacial transition zone, reduce water absorption by 17–30%, and recover 85–94% of natural aggregate concrete strength. Bio-deposition reduces water absorption by 13–21%, while acid/silica fume treatments improve late-age strength but carry environmental trade-offs. This review formulates a practice-oriented implementation framework for structural-grade RAC. Sustainability analyses indicate that carbonated RA can achieve net-positive CO₂ abatement when under low-carbon energy supply. A mechanistic schematic is presented to synthesise treatment-to-pore-structure/durability pathways across the four principal treatment routes, and a quantitative synthesis plot compares water absorption reductions across all treatment types using 13 data points drawn from included studies. A structured treatment comparison evaluates the energy intensity, industrial scalability, CO₂ footprint, and technology readiness level for each strategy. The remaining challenges include a lack of hybrid treatment studies, limited real-scale durability data, and insufficient mechanistic models linking treatment to pore structure evolution. This review recommends harmonised durability-based criteria and updates to standards (e.g., BS 8500, EN 12620) to support the scalable deployment of treated RA. Full article