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Search Results (1,028)

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Keywords = clinical trial methodology

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15 pages, 835 KiB  
Review
Optimising Exercise for Managing Chemotherapy-Induced Peripheral Neuropathy in People Diagnosed with Cancer
by Dhiaan Sidhu, Jodie Cochrane Wilkie, Jena Buchan and Kellie Toohey
Cancers 2025, 17(15), 2533; https://doi.org/10.3390/cancers17152533 - 31 Jul 2025
Viewed by 346
Abstract
Background: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise [...] Read more.
Background: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise current evidence on exercise interventions for managing chemotherapy-induced peripheral neuropathy and provide practical insights to support clinicians in integrating these approaches into patient care. Methods: A search was conducted across MEDLINE, CINAHL, and SPORTDiscus using keywords related to exercise and CIPN. Studies were included if they involved adults receiving neurotoxic chemotherapy and exercise-based interventions. Two authors independently screened studies and resolved conflicts with a third author. Study quality was assessed using the JBI Critical Appraisal Tools, and only studies meeting a minimum quality standard were included. A balanced sampling approach was employed. Data on study design, participant characteristics, interventions, and outcomes were extracted. Results: Eleven studies were included, covering various exercise modalities: multimodal (n = 5), yoga (n = 2), aerobic (n = 1), resistance (n = 1), balance (n = 1), and sensorimotor (n = 1). Exercise interventions, particularly multimodal exercise, significantly improved symptom severity, functionality, and quality of life (p < 0.05). The studies had high methodological quality, with randomised controlled trials scoring between 9/13 and 11/13, and quasi-experimental studies scoring 8/9 on JBI tools. Conclusions: This review highlights the significant benefits of exercise, especially multimodal exercise, for managing CIPN and provides guidance for integrating these strategies into clinical practice. Future research is needed to refine exercise prescriptions and develop standardised guidelines. Full article
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13 pages, 2435 KiB  
Article
Preliminary Evaluation of Spherical Over-Refraction Measurement Using a Smartphone
by Rosa Maria Salmeron-Campillo, Gines Martinez-Ros, Jose Angel Diaz-Guirado, Tania Orenes-Nicolas, Mateusz Jaskulski and Norberto Lopez-Gil
Photonics 2025, 12(8), 772; https://doi.org/10.3390/photonics12080772 (registering DOI) - 31 Jul 2025
Viewed by 205
Abstract
Background: Smartphones offer a promising tool for monitoring refractive error, especially in underserved areas where there is a shortage of eye-care professionals. We propose a novel method for measuring spherical over-refraction using smartphones. Methods: Specific levels of myopia using positive spherical trial lenses, [...] Read more.
Background: Smartphones offer a promising tool for monitoring refractive error, especially in underserved areas where there is a shortage of eye-care professionals. We propose a novel method for measuring spherical over-refraction using smartphones. Methods: Specific levels of myopia using positive spherical trial lenses, ranging from 0.00 D to 1.50 D in 0.25 D increments, were induced in 30 young participants (22 ± 5 years). A comparison was conducted between the induced over-refraction and the measurements obtained using a non-commercial mobile application based on the face–device distance measurement using the front camera while the subject was performing a resolution task. Results: Calibrated mobile app over-refraction results showed that 89.5% of the estimates had an error ≤ 0.25 D, and no errors exceeding 0.50 D. Bland–Altman analysis revealed no significant bias between app and clinical over-refraction, with a mean difference of 0.00 D ± 0.44 D (p = 0.981), indicating high accuracy and precision of the method. Conclusions: The methodology used shows high accuracy and precision in the measurement of the spherical over-refraction with only the use of a smartphone, allowing self-monitorization of potential myopia progression. Full article
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20 pages, 1220 KiB  
Systematic Review
The Evolving Role of Stem Cells in Oral Health and Regeneration: A Systematic Review
by Gianna Dipalma, Grazia Marinelli, Arianna Fiore, Liviana Balestriere, Claudio Carone, Silvio Buongiorno, Francesco Inchingolo, Giuseppe Minervini, Andrea Palermo, Angelo Michele Inchingolo and Alessio Danilo Inchingolo
Surgeries 2025, 6(3), 65; https://doi.org/10.3390/surgeries6030065 - 30 Jul 2025
Viewed by 278
Abstract
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing [...] Read more.
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article
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19 pages, 425 KiB  
Review
Taste Dysfunction in Head and Neck Cancer: Pathophysiology and Clinical Management—A Comprehensive Review
by Luigi Sardellitti, Enrica Filigheddu, Giorgio Mastandrea, Armando Di Palma and Egle Patrizia Milia
Biomedicines 2025, 13(8), 1853; https://doi.org/10.3390/biomedicines13081853 - 30 Jul 2025
Viewed by 172
Abstract
Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management [...] Read more.
Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management of taste dysfunction associated with HNC and its treatments, particularly chemotherapy and radiotherapy. Methods: A structured literature search was performed across PubMed, Scopus, and Cochrane Library for articles published between January 2015 and February 2025. Studies were included if they investigated taste dysfunction related to HNC, focusing on pathophysiological mechanisms and therapeutic interventions. A total of 47 original studies were analyzed through a narrative synthesis due to heterogeneity in study designs and outcomes. Results: Taste dysfunction in HNC patients arises from tumor-related inflammation, cytotoxic injury from chemotherapy, and radiation-induced epithelial and neural damage. Chemotherapy and radiotherapy often exert synergistic negative effects on gustatory function. Management strategies identified include dietary counselling, nutritional supplementation (zinc, lactoferrin, monosodium glutamate, miraculin), pharmacological agents targeting salivary function, and non-pharmacological interventions such as acupuncture, photobiomodulation, and reconstructive surgery. However, the evidence is limited by small sample sizes, methodological variability, and the frequent exclusion of HNC patients from broader dysgeusia trials. Reported prevalence of taste dysfunction ranged from 39% to 97.4%, with higher rates observed among patients treated with radiotherapy and chemoradiotherapy. Conclusions: Taste dysfunction remains a critical yet unmet clinical challenge in HNC patients. High-quality, targeted research is urgently needed to develop standardized assessments and evidence-based management strategies to improve patient outcomes. Full article
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19 pages, 1023 KiB  
Review
Current Evidence in Robotic Colorectal Surgery
by Franziska Willis, Anca-Laura Amati, Martin Reichert, Andreas Hecker, Tim O. Vilz, Jörg C. Kalff, Stefan Willis and Maria A. Kröplin
Cancers 2025, 17(15), 2503; https://doi.org/10.3390/cancers17152503 - 29 Jul 2025
Viewed by 135
Abstract
Colorectal surgery has undergone significant advances over the past few decades, driven by the evolution of minimally invasive techniques, particularly laparoscopy and robotics. While laparoscopy is widely recognized for its short-term benefits and oncological safety, the increasing adoption of robot-assisted surgery (RAS) has [...] Read more.
Colorectal surgery has undergone significant advances over the past few decades, driven by the evolution of minimally invasive techniques, particularly laparoscopy and robotics. While laparoscopy is widely recognized for its short-term benefits and oncological safety, the increasing adoption of robot-assisted surgery (RAS) has generated considerable debate regarding its clinical benefits, economic implications, and overall impact on patient outcomes. This narrative review synthesizes the existing evidence, highlighting the clinical and economic aspects of RAS in colorectal surgery, while exploring areas for future research. The findings suggest that RAS offers potential technical advantages, including increased precision, three-dimensional visualization, and improved ergonomics, particularly in anatomically complex scenarios such as low rectal resections. Still, its superiority over laparoscopy remains inconclusive and current evidence is mixed. For colon cancer, meta-analyses and analyses of large cohorts suggest lower conversion rates and faster recovery with RAS, although data are mostly retrospective and lack long-term oncological endpoints. In rectal cancer, emerging evidence from randomized controlled trials demonstrates improved short-term outcomes. Additionally, the recently published three-year results of the REAL trial are the first to demonstrate enhanced oncological outcomes following RAS. However, findings remain inconsistent due to methodological heterogeneity, the absence of patient stratification, and limited data on long-term survival and cost-effectiveness. The available evidence indicates that RAS may offer advantages in selected patient populations, particularly for anatomically complex procedures. Yet, its overall utility remains uncertain. Future studies should emphasize high-quality randomized trials, stratified subgroup analyses, and standardized economic evaluations to better define the role of RAS in colorectal surgery. Full article
(This article belongs to the Special Issue Robotic Surgery in Colorectal Cancer)
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17 pages, 481 KiB  
Review
Cognitive Impairment in Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Scoping Review
by João Vasco Barreira, Pedro Barreira, Gil Falcão, Daniela Garcez, Pedro Silva, Gustavo Santos, Mário Fontes-Sousa, José Leão Mendes, Filipa Reis, Carla F. Santos, Filipa Ribeiro and Manuel Luís Capelas
Cancers 2025, 17(15), 2501; https://doi.org/10.3390/cancers17152501 - 29 Jul 2025
Viewed by 256
Abstract
Background: Androgen deprivation therapy (ADT) is a primary treatment for prostate cancer (PCa) that effectively reduces androgen levels to suppress tumor progression. However, growing evidence suggests potential cognitive side effects, raising concerns about the long-term neurological consequences of this treatment. Objective: This scoping [...] Read more.
Background: Androgen deprivation therapy (ADT) is a primary treatment for prostate cancer (PCa) that effectively reduces androgen levels to suppress tumor progression. However, growing evidence suggests potential cognitive side effects, raising concerns about the long-term neurological consequences of this treatment. Objective: This scoping review aims to synthesize the existing evidence linking ADT to cognitive changes in men with PCa, identifying the key cognitive domains affected and outlining gaps in the existing literature. Methods: A systematic literature search was conducted according to the PRISMA-ScR guidelines in CINAHL, PubMed, Scopus, and Web of Science. Studies investigating cognitive function in ADT-treated PCa patients were included, covering randomized controlled trials (RCTs) and cohort, case–control, and cross-sectional studies. The extracted data included the study design, evaluated cognitive characteristics, measurement tools, and overall findings. Results: A total of 22 studies met the inclusion and exclusion criteria. Cognitive assessments varied across studies. While some studies reported cognitive impairments in ADT-treated patients—particularly in working, verbal, and visual memory and executive function—others found no significant effects. The variability in prostate cancer staging, epidemiological study designs, and treatment regimens; the exclusion of comorbid conditions; and the differences in assessment tools, sample sizes, and study durations hinder definitive conclusions about the cognitive effects of ADT. Conclusions: This scoping review highlights the heterogeneous and often contradictory evidence regarding ADT-associated cognitive dysfunction. While certain cognitive domains may be affected, methodological inconsistencies limit robust conclusions. Standardized cognitive assessments and longer longitudinal studies are required to clarify ADT’s role in cognitive decline. As the PCa survival rate increases with extended ADT use, integrating routine cognitive monitoring into clinical practice should be considered for PCa patients. Full article
(This article belongs to the Special Issue Novel Insights into Cancer-Related Cognitive Impairment)
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20 pages, 1859 KiB  
Systematic Review
From Evidence to Practice: A Systematic Review and Meta-Analysis on the Effects of Supervised Exercise on Fatigue in Breast and Prostate Cancer Survivors
by Arturo Cano-Uceda, Pablo García-Fernández, Blanca Peuyadé-Rueda, Ana María Cañuelo-Marquez, Cristian Solís-Mencía, Carmen Lucio-Allende, Luis De Sousa-De Sousa and José Luis Maté-Muñoz
Appl. Sci. 2025, 15(15), 8399; https://doi.org/10.3390/app15158399 - 29 Jul 2025
Viewed by 197
Abstract
Background: Breast and prostate cancer represent a significant global public health burden. Among the adverse effects of oncological treatments, fatigue is one of the most prevalent, persistent, and disabling symptoms. Therapeutic exercise has been shown to be effective for its management, with [...] Read more.
Background: Breast and prostate cancer represent a significant global public health burden. Among the adverse effects of oncological treatments, fatigue is one of the most prevalent, persistent, and disabling symptoms. Therapeutic exercise has been shown to be effective for its management, with supervision identified as a key factor that may enhance adherence, safety, and intensity control. This systematic review and meta-analysis aimed to compare the effects of supervised exercise programs versus usual care on cancer-related fatigue in patients with breast or prostate cancer. Methods: A systematic search (September–December 2024) was conducted in six databases (PubMed, Web of Science, Scopus, Cochrane, PEDro, Scielo), selecting RCTs from the past 10 years in English or Spanish. Studies compared supervised exercise with unsupervised exercise or usual care in stage I–III breast or prostate cancer patients within five years post-treatment. Methodological quality was assessed with the PEDro scale and risk of bias with Cochrane’s RoB 2.0. A random-effects model was used to calculate pooled effect sizes (ES, 95% CI), with heterogeneity (I2), sensitivity, subgroup, and publication bias analyses. Results: A total of 25 interventions from 19 randomized controlled trials involving over 2200 participants were included. Supervised exercise significantly reduced cancer-related fatigue compared to usual care (effect size = 0.34; 95% CI: 0.22–0.47; p < 0.001; I2 = 56%). Sensitivity analyses supported the robustness of the findings. Subgroup analyses revealed greater effects in combined exercise programs, in men, and in patients with prostate cancer. No evidence of publication bias was observed. While 73.7% of studies were rated as having good methodological quality, the risk of bias was often unclear or high. Conclusions: Supervised therapeutic exercise programs are effective and safe for reducing fatigue in breast and prostate cancer survivors. These interventions should be incorporated into comprehensive care plans, with individualization based on patients’ clinical and demographic characteristics. Further research is needed to identify the most effective and sustainable strategies for different patient subgroups. Full article
(This article belongs to the Special Issue Recent Advances in Exercise-Based Rehabilitation)
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18 pages, 1445 KiB  
Systematic Review
Topical Use of Tacrolimus in Corneal and Ocular Surface Pathologies: A Systematic Review
by Georgios Katonis, Argyrios Tzamalis, Ioannis Tsinopoulos and Nikolaos Ziakas
J. Clin. Med. 2025, 14(15), 5347; https://doi.org/10.3390/jcm14155347 - 29 Jul 2025
Viewed by 309
Abstract
Background/Objectives: Tacrolimus, an immunosuppressant, is increasingly used topically in ophthalmology, particularly for conditions like vernal keratoconjunctivitis and post-keratoplasty rejection prophylaxis. This systematic review aims to evaluate the efficacy and safety of topical tacrolimus in these ocular conditions. Methods: A thorough search [...] Read more.
Background/Objectives: Tacrolimus, an immunosuppressant, is increasingly used topically in ophthalmology, particularly for conditions like vernal keratoconjunctivitis and post-keratoplasty rejection prophylaxis. This systematic review aims to evaluate the efficacy and safety of topical tacrolimus in these ocular conditions. Methods: A thorough search was conducted in PubMed and Cochrane Library for relevant studies published up to 16 March 2025. Studies were eligible for inclusion if they were randomized controlled trials investigating topical tacrolimus in human ocular disease, were published in English, and reported clearly defined outcomes. Exclusion criteria included non-randomized studies, animal studies, systemic treatments, non-English publications, and studies lacking clearly reported outcomes. Data regarding study design, patient demographics, intervention details, and outcomes were extracted and analyzed. The Cochrane risk-of-bias tool (RoB 2.0) was used to assess the risk of bias. Results: A total of 10 studies met the inclusion criteria, were retrieved, and were categorized as not highly biased after the risk-of-bias assessment. These studies were included in the systematic review, where a qualitative analysis took place. Our analysis revealed that the topical use of tacrolimus showed promising results, as it improved clinical signs and symptoms in most patients. In half of the studies, tacrolimus demonstrated superior efficacy compared to the control group, while in the remaining studies, it showed equivalent efficacy. Adverse effects, such as a burning sensation, were noted in 7/10 studies but were generally mild. The methodologies were somewhat heterogeneous, and some studies had small sample sizes. Conclusions: Topical tacrolimus shows promising effects in managing various ocular surface diseases. While randomized controlled trials provide evidence, further research with larger sample sizes is necessary to solidify its efficacy and safety profile compared to other immunosuppressants. Full article
(This article belongs to the Special Issue Advancements in Cornea Transplantation)
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51 pages, 1874 KiB  
Review
Parkinson’s Disease: Bridging Gaps, Building Biomarkers, and Reimagining Clinical Translation
by Masaru Tanaka
Cells 2025, 14(15), 1161; https://doi.org/10.3390/cells14151161 - 28 Jul 2025
Viewed by 746
Abstract
Parkinson’s disease (PD), a progressive neurodegenerative disorder, imposes growing clinical and socioeconomic burdens worldwide. Despite landmark discoveries in dopamine biology and α-synuclein pathology, translating mechanistic insights into effective, personalized interventions remains elusive. Recent advances in molecular profiling, neuroimaging, and computational modeling have broadened [...] Read more.
Parkinson’s disease (PD), a progressive neurodegenerative disorder, imposes growing clinical and socioeconomic burdens worldwide. Despite landmark discoveries in dopamine biology and α-synuclein pathology, translating mechanistic insights into effective, personalized interventions remains elusive. Recent advances in molecular profiling, neuroimaging, and computational modeling have broadened the understanding of PD as a multifactorial systems disorder rather than a purely dopaminergic condition. However, critical gaps persist in diagnostic precision, biomarker standardization, and the translation of bench side findings into clinically meaningful therapies. This review critically examines the current landscape of PD research, identifying conceptual blind spots and methodological shortfalls across pathophysiology, clinical evaluation, trial design, and translational readiness. By synthesizing evidence from molecular neuroscience, data science, and global health, the review proposes strategic directions to recalibrate the research agenda toward precision neurology. Here I highlight the urgent need for interdisciplinary, globally inclusive, and biomarker-driven frameworks to overcome the fragmented progression of PD research. Grounded in the Accelerating Medicines Partnership-Parkinson’s Disease (AMP-PD) and the Parkinson’s Progression Markers Initiative (PPMI), this review maps shared biomarkers, open data, and patient-driven tools to faster personalized treatment. In doing so, it offers actionable insights for researchers, clinicians, and policymakers working at the intersection of biology, technology, and healthcare delivery. As the field pivots from symptomatic relief to disease modification, the road forward must be cohesive, collaborative, and rigorously translational, ensuring that laboratory discoveries systematically progress to clinical application. Full article
(This article belongs to the Special Issue Exclusive Review Papers in Parkinson's Research)
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17 pages, 597 KiB  
Review
Dry Needling for Tension-Type Headache: A Scoping Review on Intervention Procedures, Muscle Targets, and Outcomes
by Ana Bravo-Vazquez, Ernesto Anarte-Lazo, Cleofas Rodriguez-Blanco and Carlos Bernal-Utrera
J. Clin. Med. 2025, 14(15), 5320; https://doi.org/10.3390/jcm14155320 - 28 Jul 2025
Viewed by 265
Abstract
Background/Objectives: Tension-type headache (TTH) is the most prevalent form of primary headache. The etiology of TTH is not yet fully understood, although it is associated with the presence of myofascial trigger points (MTPs) in cervical and facial muscles. Dry needling (DN) therapy [...] Read more.
Background/Objectives: Tension-type headache (TTH) is the most prevalent form of primary headache. The etiology of TTH is not yet fully understood, although it is associated with the presence of myofascial trigger points (MTPs) in cervical and facial muscles. Dry needling (DN) therapy has emerged as an effective and safe non-pharmacological option for pain relief, but there are a lack of systematic reviews focused on its specific characteristics in TTH. The aim of this paper is to examine the characteristics and methodologies of DN in managing TTH. Methods: A scoping review was conducted with inclusion criteria considering studies that evaluated DN interventions in adults with TTH, reporting target muscles, diagnostic criteria, and technical features. The search was performed using PubMed, Embase, Scopus, and the Web of Science, resulting in the selection of seven studies after a rigorous filtering and evaluation process. Results: The included studies, primarily randomized controlled trials, involved a total of 309 participants. The most frequently treated muscles were the temporalis and trapezius. Identification of MTPs was mainly performed through manual palpation, although diagnostic criteria varied. DN interventions differed in technique. All studies included indicated favorable outcomes with improvements in headache symptoms. No serious adverse effects were reported, suggesting that the technique is safe. However, heterogeneity in protocols and diagnostic criteria limits the comparability of results. Conclusions: The evidence supports the use of DN in key muscles such as the temporalis and trapezius for managing TTH, although the diversity in methodologies and diagnostic criteria highlights the need for standardization. The safety profile of the method is favorable, but further research is necessary to define optimal protocols and improve reproducibility. Implementing objective diagnostic criteria and uniform protocols will facilitate advances in clinical practice and future research, ultimately optimizing outcomes for patients with TTH. Full article
(This article belongs to the Section Clinical Neurology)
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40 pages, 1378 KiB  
Systematic Review
Liquid Biopsy Biomarkers in Metastatic Castration-Resistant Prostate Cancer Treated with Second-Generation Antiandrogens: Ready for Clinical Practice? A Systematic Review
by Andrei-Vlad Badulescu, Razvan Rahota, Alon Vigdorovits and Ovidiu Laurean Pop
Cancers 2025, 17(15), 2482; https://doi.org/10.3390/cancers17152482 - 27 Jul 2025
Viewed by 406
Abstract
Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for [...] Read more.
Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy. Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts). Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry. Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations. Full article
(This article belongs to the Special Issue Recent Advances in Liquid Biopsy Biomarkers of Cancer)
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17 pages, 4394 KiB  
Article
Nonclinical Human Cardiac New Approach Methodologies (NAMs) Predict Vanoxerine-Induced Proarrhythmic Potential
by M. Iveth Garcia, Bhavya Bhardwaj, Keri Dame, Verena Charwat, Brian A. Siemons, Ishan Goswami, Omnia A. Ismaiel, Sabyasachy Mistry, Tromondae K. Feaster, Kevin E. Healy, Alexandre J. S. Ribeiro and Ksenia Blinova
J. Cardiovasc. Dev. Dis. 2025, 12(8), 285; https://doi.org/10.3390/jcdd12080285 - 26 Jul 2025
Viewed by 422
Abstract
New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II [...] Read more.
New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II clinical trials, events of QT prolongation or proarrhythmia were not observed. Here, we utilized cardiac NAMs to evaluate the functional consequences of vanoxerine treatment on human cardiac excitation–contraction coupling. The cardiac MPS used in this study was a microfabricated fluidic culture platform with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) capable of evaluating voltage, intracellular calcium handling, and contractility. Likewise, the hiPSC-CM comprehensive in vitro proarrhythmia assay (CiPA) was employed based on multielectrode array (MEA). Vanoxerine treatment delayed repolarization in a concentration-dependent manner and induced proarrhythmic events in both NAM platforms. The complex cardiac MPS displayed a frequency-dependent vanoxerine response such that EADs were eliminated at a faster pacing rate (1.5 Hz). Moreover, exposure analysis revealed a 99% vanoxerine loss in the cardiac MPS. TdP risk analysis demonstrated high to intermediate TdP risk at clinically relevant concentrations of vanoxerine and frequency-independent EAD events in the hiPSC-CM CiPA model. These findings demonstrate that nonclinical cardiac NAMs can recapitulate clinical outcomes, including detection of vanoxerine-induced delayed repolarization and proarrhythmic effects. Moreover, this work provides a foundation to evaluate the safety and efficacy of novel compounds to reduce the dependence on animal studies. Full article
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18 pages, 3945 KiB  
Review
Association of Lycopene and Male Reproductive Health: Systematic Review and Meta-Analysis
by Isabel Viña and Juan R. Viña
Int. J. Mol. Sci. 2025, 26(15), 7224; https://doi.org/10.3390/ijms26157224 - 25 Jul 2025
Viewed by 595
Abstract
Lycopene, a carotenoid found in tomatoes and watermelon, has been investigated for its potential to improve male fertility through its antioxidant and anti-inflammatory mechanisms. However, evidence of its effectiveness remains inconsistent. We conducted a systematic review and meta-analysis of studies published until February [...] Read more.
Lycopene, a carotenoid found in tomatoes and watermelon, has been investigated for its potential to improve male fertility through its antioxidant and anti-inflammatory mechanisms. However, evidence of its effectiveness remains inconsistent. We conducted a systematic review and meta-analysis of studies published until February 2025 in the PubMed, Scopus, Web of Science, and Medline databases. Clinical studies evaluating lycopene supplementation in relation to male fertility outcomes were included in this review. Standardized mean differences (SMDs) were calculated for the key outcomes. Four clinical studies involving 151 participants were included. Lycopene supplementation significantly improved sperm concentration (SMD 0.33, 95% CI [0.02–0.65], p = 0.037) and nonprogressive motility (SMD 0.45, 95% CI [0.04–0.87], p = 0.032). No statistically significant effects were observed on total motility, progressive motility, normal or abnormal morphology, semen volume, or DNA damage. Sensitivity analyses showed that the findings were generally robust, although publication bias and methodological heterogeneity were noted. Lycopene supplementation may offer modest benefits in improving sperm concentration and nonprogressive motility in men. However, evidence for other fertility-related outcomes is inconclusive. Larger, high-quality randomized trials are needed to confirm these findings and clarify the role of lycopene in male reproductive health. Full article
(This article belongs to the Special Issue Advanced Research in Immunotoxicity and Oxidative Stress)
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35 pages, 2501 KiB  
Article
Adaptive Bayesian Clinical Trials: The Past, Present, and Future of Clinical Research
by Donald A. Berry
J. Clin. Med. 2025, 14(15), 5267; https://doi.org/10.3390/jcm14155267 - 25 Jul 2025
Viewed by 215
Abstract
Background/Objectives: Decision-analytic Bayesian approaches are ideally suited for designing clinical trials. They have been used increasingly over the last 30 years in developing medical devices and drugs. A prototype trial is a bandit problem in which treating participants is as important as treating [...] Read more.
Background/Objectives: Decision-analytic Bayesian approaches are ideally suited for designing clinical trials. They have been used increasingly over the last 30 years in developing medical devices and drugs. A prototype trial is a bandit problem in which treating participants is as important as treating patients in clinical practice after the trial. Methods: This article chronicles the use of the Bayesian approach in clinical trials motivated by bandit problems. It provides a comprehensive historical and practical review of Bayesian adaptive trials, with a focus on bandit-inspired designs. Results: The 20th century saw advances in Bayesian methodology involving computer simulation. In the 21st century, methods motivated by bandit problems have been applied in designing scores of actual clinical trials. Fifteen such trials are described. By far the most important Bayesian contributions in clinical trials are the abilities to observe the accumulating results and to modify the future course of the trial on the basis of these observations. In the spirit of artificial intelligence, algorithms are programmed to learn the optimal treatment assignments over the remainder of the trial. Conclusions: Bayesian trials are still nascent and represent a small minority of clinical trials, but their existence is changing the way investigators, regulators, and government and industry sponsors view innovation in clinical trials. Full article
(This article belongs to the Special Issue The Role of Bayesian Methods in Clinical Medicine)
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19 pages, 5345 KiB  
Article
Identification of Novel Biomarkers in Huntington’s Disease Based on Differential Gene Expression Meta-Analysis and Machine Learning Approach
by Nayan Dash, Md Abul Bashar, Jeonghan Lee and Raju Dash
Appl. Sci. 2025, 15(15), 8286; https://doi.org/10.3390/app15158286 - 25 Jul 2025
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Abstract
Huntington’s disease (HD) is a severe and progressive neurodegenerative disease for which therapeutic options have so far been confined to symptomatic treatment. Currently, the diagnosis relies on the signs and symptoms shown by patients; however, by that stage, the psychomotor issues have progressed [...] Read more.
Huntington’s disease (HD) is a severe and progressive neurodegenerative disease for which therapeutic options have so far been confined to symptomatic treatment. Currently, the diagnosis relies on the signs and symptoms shown by patients; however, by that stage, the psychomotor issues have progressed to a point where reversal of the condition is unattainable. Although numerous clinical trials have been actively investigating therapeutic agents aimed at preventing the onset of disease or slowing down the disease progression, there has been a constant need for reliable biomarkers to assess neurodegeneration, monitor disease progression, and assess the efficacy of treatments accurately. Therefore, to discover the key biomarkers associated with the progression of HD, we employed bioinformatics and machine learning (ML) to create a robust pipeline that integrated differentially expressed gene (DEG) analysis with ML to select potential biomarkers. We performed a meta-analysis to identify DEGs using three Gene Expression Omnibus (GEO) microarray datasets from different platforms related to HD-affected brain tissue, applying both relaxed and strict criteria to identify differentially expressed genes. Subsequently, focusing only on genes identified through the inclusive threshold, we employed 19 diverse ML techniques to explore the common genes that contributed to the top three selected ML algorithms and the shared genes that had an impact on the ML algorithms and were observed in the meta-analysis using the stringent condition were selected. Additionally, a receiver operating characteristic (ROC) analysis was conducted on external datasets to validate the discriminatory power of the identified genes. Based on the results of an inverse variance weighted meta-analysis of the AUCs across both human and mouse cohorts, GABRD and PHACTR1 were identified as the most robust candidates and were selected as key biomarkers for HD. Our comprehensive methodology, which integrates DEG meta-analysis with ML techniques, enabled a systematic prioritization of these biomarkers, providing valuable insights into their biological significance and potential for further validation in clinical research. Full article
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