Search Results (7,805)

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows. Full article

Background: This systematic review evaluates the efficacy of rehabilitation-focused exercise interventions for lumbar degenerative disc disease (DDD), a leading cause of chronic low back pain. Methods: Following PRISMA guidelines, a comprehensive search was conducted across international and regional databases (PubMed, Scopus, Web of Science, Magiran, SID, and Noormags) covering the period from January 2010 to January 2025. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251088811. Using keywords such as “lumbar DDD,” “exercise therapy,” and “rehabilitation,” a total of 2495 records were identified. After screening, 20 studies—including clinical trials, quasi-experimental, and experimental designs—met the inclusion criteria and were assessed using the McMaster Critical Review Form for Quantitative Studies. Results: Interventions such as hydrotherapy, core stability training, Pilates, and suspension exercises were found to significantly reduce pain and improve functional outcomes. While multimodal approaches (e.g., aquatic exercise combined with acupuncture) showed positive effects, the comparative studies revealed no significant differences between modalities. Suspension training demonstrated superior efficacy in pain reduction compared to isolated core stability exercises. The methodological quality of included studies ranged from good to excellent, with the majority rated as very good or excellent (McMaster scores: 8 “excellent,” 7 “very good,” and 5 “good”). Common limitations among the studies included methodological heterogeneity, small sample sizes (n = 14–30), and insufficient long-term follow-up. Conclusions: Exercise-based rehabilitation is an effective strategy for managing lumbar DDD. Evidence particularly supports the use of suspension training and aquatic therapy for superior improvements in pain and functional outcomes. Future research should aim to adopt standardized protocols, recruit larger sample sizes, and include extended follow-up periods to produce more robust and generalizable findings. Full article

(1) Background: Early palliative care (EPC) is increasingly recognized as a key component of comprehensive cancer management, with evidence supporting improvements in quality of life, symptom control, and clinical outcomes in advanced malignancies. (2) Methods: This systematic review followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024623219). We searched PubMed, Embase, and the Cochrane CENTRAL Library for randomized controlled trials (RCTs) evaluating EPC in adults with advanced, incurable, or metastatic cancer. Eligible studies reported on at least one of the following: overall quality of life, symptom burden, or disease progression indicators. (3) Results: Forty-one RCTs met inclusion criteria. Despite heterogeneity in timing and structure, EPC consistently improved quality of life and reduced symptom burden in advanced cancer patients, with 32 trials demonstrating significant clinical benefit. Some studies also reported slowed disease progression. However, several RCTs showed no significant effects, highlighting variation in outcomes, possible subgroup effects, and challenges in implementation. Definitions and delivery of EPC varied widely, particularly in timing, frequency, and integration into oncology care. (4) Conclusions: These findings support the integration of EPC alongside disease-directed treatments, challenging the misconception that palliative care is only appropriate at the end of life and reinforcing its role early in the cancer care continuum. Full article

Background: Plant-based protein supplementation in supporting muscle recovery following resistance exercise remains an area of growing interest, particularly among vegan athletes, as a potential alternative to animal-based proteins. This systematic review aimed to evaluate the effectiveness of plant-based proteins on recovery from resistance exercise-induced muscle damage in healthy young adults. Methods: A systematic and comprehensive search was administered in eight databases up to 1 May 2025, identifying 1407 articles. Following deduplication and screening, 24 studies met the eligibility criteria, including 22 randomized controlled trials and 2 non-randomized studies, with the majority from high income western countries. Results: Interventions primarily involved soy, pea, rice, hemp, potato, and blended plant protein sources, with doses ranging from 15 to 50 g, typically administered post resistance exercise. Outcomes assessed included muscle protein synthesis (MPS), delayed-onset muscle soreness (DOMS), inflammatory biomarkers, muscle function, and fatigue. The review findings reaffirm that single-source plant proteins generally offer limited benefits compared to animal proteins such as whey, particularly in acute recovery settings, a limitation well-documented consistently in the literature. However, our synthesis highlights that well-formulated plant protein blends (e.g., combinations of pea, rice, and canola) can stimulate MPS at levels comparable to whey when consumed at adequate doses (≥30 g with ~2.5 g leucine). Some studies also reported improvements in subjective recovery outcomes and reductions in muscle damage biomarkers with soy or pea protein. However, overall evidence remains limited by small sample sizes, moderate to high risk of bias, and heterogeneity in intervention protocols, protein formulations, and outcome measures. Risk of bias assessments revealed concerns related to detection and reporting bias in nearly half the studies. Due to clinical and methodological variability, a meta-analysis was not conducted. Conclusion: plant-based proteins particularly in the form of protein blends and when dosed appropriately, may support muscle recovery in resistance-trained individuals and offer a viable alternative to animal-based proteins. However, further high-quality, long-term trials in vegan populations are needed to establish definitive recommendations for plant protein use in sports nutrition. Full article

Smart walking aids represent a growing trend in assistive technologies designed to support individuals with mobility impairments in their daily lives and rehabilitation. Previous research has introduced sensor-integrated systems that provide user feedback to enhance safety and functional mobility. However, a comprehensive overview of their technological and functional characteristics is lacking. To address this gap, this scoping review systematically mapped the current state of research in sensor-based walking aids, focusing on device types, sensor technologies, application contexts, target populations, and reported outcomes. In addition, integrated artificial intelligence (AI)-based approaches for functional support and health monitoring were examined. Following PRISMA-ScR guidelines, 35 peer-reviewed articles were identified from three databases: ACM Digital Library, IEEE Xplore, and Web of Science. Extracted data were thematically analyzed and synthesized across device types (e.g., walking canes, crutches, walkers, rollators) and use cases, including gait training, fall prevention, and daily support. Findings show that, while many prototypes show promising features, few have been evaluated in clinical settings or over extended periods. A lack of standardized methods for sensor location assessment, often the superficial implementation of feedback modalities, and limited integration with other assistive technologies were identified. In addition, system validation and user testing lack consensus, with few long-term studies and often incomplete demographic data. Diversity in data communication approaches and the heterogeneous use of AI algorithms were also notable. The review highlights key challenges and research opportunities to guide the future development of intelligent, user-centered mobility systems. Full article

Background/Objectives: Invasive coronary angiography (ICA) is the gold standard for the diagnosis of coronary artery disease (CAD), with various non-invasive imaging modalities also available. Machine learning (ML) methods are increasingly applied to overcome the limitations of diagnostic imaging by improving accuracy and observer independent performance. Methods: This meta-analysis (PRISMA method) summarizes the evidence for ML-based analyses of coronary imaging data from ICA, coronary computed tomography angiography (CT), and nuclear stress perfusion imaging (SPECT) to predict clinical outcomes and performance for precise diagnosis. We searched for studies from Jan 2012–March 2023. Study-reported c index values and 95% confidence intervals were used. Subgroup analyses separated models by outcome. Combined effect sizes using a random-effects model, test for heterogeneity, and Egger’s test to assess publication bias were considered. Results: In total, 46 studies were included (total subjects = 192,561; events = 31,353), of which 27 had sufficient data. Imaging modalities used were CT (n = 34), ICA (n = 7) and SPECT (n = 5). The most frequent study outcome was detection of stenosis (n = 11). Classic deep neural networks (n = 12) and convolutional neural networks (n = 7) were the most used ML models. Studies aiming to diagnose CAD performed best (0.85; 95% CI: 82, 89); models aiming to predict clinical outcomes performed slightly lower (0.81; 95% CI: 78, 84). The combined c-index was 0.84 (95% CI: 0.81–0.86). Test of heterogeneity showed a high variation among studies (I² = 97.2%). Egger’s test did not indicate publication bias (p = 0.485). Conclusions: The application of ML methods to diagnose CAD and predict clinical outcomes appears promising, although there is lack of standardization across studies. Full article

Focal chondral defects of the knee are a common cause of pain and functional limitation in active individuals and may predispose to early degenerative joint changes. Given the limited regenerative capacity of hyaline cartilage, biologically based surgical strategies have emerged to promote tissue repair and restore joint function. This narrative review critically examines current treatment approaches that rely on autologous cell sources and scaffold-supported regeneration. Particular emphasis is placed on techniques that stimulate endogenous repair or support chondrocyte-based tissue restoration through the use of autologous biomaterial constructs. The influence of lesion morphology, joint biomechanics, and patient-specific variables on treatment selection is discussed in detail, focusing on the differences between tibiofemoral and patellofemoral involvement. Biologically driven approaches have shown promising mid- to long-term outcomes in selected patients, and are increasingly favoured over traditional methods in specific clinical scenarios. However, the literature remains limited by heterogeneity in study design, follow-up duration, and outcome measures. This review aims to provide an evidence-based, morphology-informed framework to support the clinical decision-making process in the management of knee cartilage defects. Full article

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Background: Reverse total shoulder arthroplasty (RTSA) is increasingly used for managing cuff tear arthropathy, osteoarthritis, complex fractures, and revision procedures. As the demand for surgical precision and reproducibility grows, immersive technologies such as virtual reality (VR), augmented reality (AR), and metaverse-based platforms are being explored for surgical training, intraoperative guidance, and rehabilitation. While early data suggest potential benefits, a focused synthesis specific to RTSA is lacking. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Scopus, and Cochrane Library databases was performed through 30 May 2025. Eligible studies included those evaluating immersive technologies in the context of RTSA for skill acquisition or intraoperative guidance. Only peer-reviewed articles published in English were included. Data were synthesized narratively due to heterogeneity in study design and outcome metrics. Results: Out of 628 records screened, 21 studies met the inclusion criteria. Five studies evaluated immersive VR for surgical training: four randomized controlled trials and one retrospective case series. VR training improved procedural efficiency and showed non-inferiority to cadaveric training. Sixteen studies investigated intraoperative navigation or AR guidance. Clinical and cadaveric studies consistently reported improved accuracy in glenoid baseplate positioning with reduced angular and linear deviations in postoperative controls as compared to preoperative planning. Conclusions: Immersive technologies show promise in enhancing training, intraoperative accuracy, and procedural consistency in RTSA. VR and AR platforms may support standardized surgical education and precision-based practice, but their broad clinical impact remains limited by small sample sizes, heterogeneous methodologies, and limited long-term outcomes. Further multicenter trials with standardized endpoints and cost-effectiveness analyses are warranted. Postoperative rehabilitation using immersive technologies in RTSA remains underexplored and presents an opportunity for future research. Full article

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with high recurrence rates and limited curative options in metastatic settings. Cancer vaccines represent an emerging immunotherapeutic approach that aims to stimulate robust, tumor-specific immune responses. This review summarizes the current state of CRC vaccine development, including tumor cell-based, dendritic cell-based, peptide-based, nucleic acid-based (DNA and mRNA), and virus-based platforms. We highlight findings from key clinical trials that demonstrate immunogenicity, safety, and preliminary efficacy, with particular attention to combinations with chemotherapy and immune checkpoint inhibitors. Furthermore, we explore critical challenges such as tumor heterogeneity, immunosuppressive tumor microenvironments, and the logistical complexity; in this context, we particularly focus on the current development of personalized cancer vaccines, exploring the newly identified encouraging epitopes and their safety and efficacy in recent trials. The integration of cancer vaccines with in silico modeling, advanced delivery systems such as nanoparticles or AI-guided designs, and microbiome modulation represents a promising avenue for enhancing their clinical utility. Overall, therapeutic and prophylactic cancer vaccines may soon contribute meaningfully to the comprehensive management of CRC, especially in settings of minimal residual disease or early recurrence. Full article