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Analysis of VHL-dependent SCD5 regulation and its biological function in clear cell renal cell carcinoma cells
What is the added value of handsearching Hungarian medical journals and grey literature for identifying controlled clinical trials? Protocol for a meta-epidemiological study
Introduction Randomised controlled trials (RCTs) are considered the gold standard for evaluating the efficacy and safety of healthcare interventions. For valid systematic reviews and evidence-based clinical guidelines, it is essential that results of all eligible RCTs are accessible. However, articles about trials published in languages other than English are often not listed in well-known and open trial databases like Medline and therefore scarcely findable. Handsearching national journals is an important approach to identify these articles and enhance their global visibility. Consequently, the results of trials conducted and published in non-English-speaking countries are not lost but rather integrated into the global body of evidence.The present study aims to evaluate the benefits of extensive handsearching in Hungary and to identify key medical fields for future efforts. We will also assess the extent of grey literature in Hungary. We will appraise the risk of bias in the identified RCTs and controlled clinical trials (CCTs; indicating quasi-randomised or possibly randomised controlled trials) and examine the reporting quality of articles in Hungarian medical journals. Additionally, we will explore whether the automation tool Paperfetcher, recommended by Cochrane for handsearching, can effectively support these efforts in a non-English language context.Methods and analysis We will conduct a cover-to-cover handsearch of all Hungarian medical journals publishing content in the year 2023 to identify all controlled clinical trials, including RCTs, CCTs and non-RCTs, which are trials that use a clearly non-random method for allocating participants to groups. We will also search conference proceedings submitted to the Hungarian National Széchényi Library, abstract supplements from journals available via the Hungarian Medical Bibliography database, preprints available on medRxiv, Hungarian theses and dissertations, as well as Google Scholar to identify grey literature.Two independent researchers will screen the identified records, assess their eligibility, extract data and evaluate the risk of bias and reporting quality according to the CONSORT statement. To verify the availability of reports and publications derived from the identified trials in electronic databases, we will systematically search MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Scopus. All identified RCTs and CCTs not yet included in CENTRAL will be added to the database. Additionally, we will compare handsearching supported by the Paperfetcher tool with unsupported handsearching to evaluate the tool’s effectiveness in a Hungarian language context.Ethics and dissemination Since the publication resulting from the handsearching activity is a retrospective review of publicly available sources of evidence, ethical approval is not required. The study findings will be submitted for publication in a peer-reviewed journal and will be presented at international conferences
veneeR: Quantifying the ready-to-use veneer volume of European beech trees in the stand based on TLS data
Spatially precise activation of the mouse cochlea with a multi-channel hybrid cochlear implant
Objective. Cochlear implants are among the few clinical interventions for people with severe or profound hearing loss. However, current spread during monopolar electrical stimulation results in poor spectral resolution, prompting the exploration of optical stimulation as an alternative approach. Enabled by introducing light-sensitive ion channels into auditory neurons (optogenetics), optical stimulation has been shown to activate a more discrete neural area with minimal overlap between each frequency channel during simultaneous stimulation. However, the utility of optogenetic approaches is uncertain due to the low fidelity of responses to light and high-power requirements compared to electrical stimulation. Approach. Hybrid stimulation, combining sub-threshold electrical and optical pulses, has been shown to improve fidelity and use less light, but the impact on spread of activation and channel summation using a translatable, multi-channel hybrid implant is unknown. This study examined these factors during single channel and simultaneous multi-channel hybrid stimulation in transgenic mice expressing the ChR2/H134R opsin. Acutely deafened mice were implanted with a hybrid cochlear array containing alternating light emitting diodes and platinum electrode rings. Spiking activity in the inferior colliculus was recorded during electrical-only or hybrid stimulation in which optical and electrical stimuli were both at sub-threshold intensities. Thresholds, spread of activation, and threshold shifts during simultaneous hybrid stimulation were compared to electrical-only stimulation. Main results. The electrical current required to reach activation threshold during hybrid stimulation was reduced by 7.3 dB compared to electrical-only stimulation (p < 0.001). The activation width measured at two levels of discrimination above threshold and channel summation during simultaneous hybrid stimulation were significantly lower compared to electrical-only stimulation (p < 0.05), but there was no spatial advantage of hybrid stimulation at higher electrical stimulation levels. Significance. Reduced channel interaction would facilitate multi-channel simultaneous stimulation, thereby enhancing the perception of temporal fine structure which is crucial for music and speech in noise
How does ceramic-based scaffold microarchitecture impact maxillofacial bone regeneration? A systematic review of large animal models
Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or implant-related complications. Effective treatment involves scaffold designs that support vascularization, bone formation, and sufficient mechanical strength. This systematic review aims to assess whether ceramic-based scaffold properties, including porosity, pore size, and macroscopic characteristics, improve vascularization, bone formation, and the mechanical properties in the treatment of CSBDs in large animal models. A search of databases (PubMed, Embase, and Web of Science) identified 11 in vivo studies involving CSBDs (>2 cm), ceramic scaffolds, and histological analysis. Findings indicate that scaffolds with porosity exceeding 50% yield optimal outcomes by striking a balance between cell infiltration and mechanical stability. Pore sizes ranging from 300 μm to 700 μm are ideal for vascularization and bone ingrowth. Three-dimensional (3D) printing shows promise in creating scaffolds with precise and reproducible features. However, the studies varied significantly in their methodologies and outcomes, with no consensus on the optimal scaffold properties for mandibular CSBDs. Scaffold porosity and pore size play key roles in promoting vascularization and bone regeneration. Various animal models reinforce this finding, suggesting that scaffold architecture is crucial for biological integration and functional outcomes. This review highlights the importance of standardized research protocols and clear design criteria in enhancing the success of bone regeneration. Future research should investigate emerging biomaterials and new scaffold technologies to overcome current limitations in clinical applications
Intraoperative confocal laser endomicroscopy detects prostate cancer at the single-cell level with high specificity and in real time: a preclinical proof of concept
In prostate cancer (PCa) surgery, precise tumor margin identification remains challenging despite advances in surgical techniques. This study evaluates the combination of tumor-specific near-infrared imaging with the PSMA-targeting molecule PSMA-914 and optical endomicroscopy (NIR-pCLE) for single-cell-level tumor identification in a preclinical proof of concept. Methods: NIR-pCLE imaging of varying PSMA-914 concentrations was performed on PSMA-positive LNCaP and PSMA-negative PC-3 cells using Cellvizio® 100 with pCLE Confocal Miniprobes™. To identify optimal PSMA-914 dosing for in vivo imaging, different doses (0–10 nmol) were evaluated using NIR-pCLE, Odyssey CLx imaging, and confocal microscopy in an LNCaP tumor-bearing xenograft model. A proof of concept mimicking a clinical workflow was performed using 5 nmol [68Ga]Ga-PSMA-914 in LNCaP and PC-3 tumor xenografts, including PET/MRI, in/ex vivo NIR-pCLE imaging, and microscopic/macroscopic imaging. Results: NIR-pCLE detected PSMA-specific fluorescence at concentrations above 30 nM in vitro. The optimal dose was identified as 5 nmol PSMA-914 for NIR-pCLE imaging with cellular resolution in LNCaP xenografts. PET/MRI confirmed high tumor uptake and a favorable distribution profile of PSMA-914. NIR-pCLE imaging enabled real-time, single-cell-level detection of PSMA-positive tissue, visualizing tumor heterogeneity, confirmed by ex vivo microscopy and imaging. Conclusions: This preclinical proof of concept demonstrates the potential of intraoperative PSMA-specific NIR-pCLE imaging to visualize tissue structures in real time at cellular resolution. Clinical implementation could provide surgeons with valuable additional information, potentially advancing PCa patient care through improved surgical precision
Metabolic surgery reduces CRC disease progression through circulating bile acid diversion
Nephrolink: relational embeddings for medical data analysis using llm-extracted patient-specific knowledge graphs and graph attention networks
Sonography of salivary gland tumors and disorders
Diseases of the salivary glands are as common as they are diverse and can have different causes. Clinicians can differentiate salivary gland changes based on chronic systemic diseases, congenital and vascular malformations, and benign and malignant tumors. Acute infectious pathologies can also arise as a result of obstructive pathologies. A large number of diseases with similar clinical presentations have to be differentiated. Due to the improved resolution of ultrasound technology over the last 20 years, it is now used as the first imaging modality to examine salivary gland pathologies. It allows a quick, dynamic, and non-invasive examination of the salivary glands and the soft tissue of the neck. In order to accurately diagnose and treat patients, a very good knowledge of these diseases and their appearance on sonography is required