Search Results (22,640)

Background: This study focuses on the critical task of blood vessel segmentation in medical image analysis, essential for diagnosing cardiovascular diseases and enabling effective treatment planning. Although deep learning architectures often produce very high segmentation results in medical images, coronary computed tomography angiography (CTA) images are more challenging than invasive coronary angiography (ICA) images due to noise and the complexity of vessel structures. Methods: Classical architectures for medical images, such as U-Net, achieve only moderate accuracy, with an average Dice score of 0.722. Results: This study introduces Morpho-U-Net, an enhanced U-Net architecture that integrates advanced morphological operations, including Gaussian blurring, thresholding, and morphological opening/closing, to improve vascular integrity, reduce noise, and achieve a higher Dice score of 0.9108, a precision of 0.9341, and a recall of 0.8872. These enhancements demonstrate superior robustness to noise and intricate vessel geometries. Conclusions: This pre-processing filter effectively reduces noise by grouping neighboring pixels with similar intensity values, allowing the model to focus on relevant anatomical structures, thus outperforming traditional methods in handling the challenges posed by CTA images. Full article

Introduction: Graphene, a two-dimensional arrangement of carbon atoms, has drawn significant interest in medical research due to its unique properties. In the context of bone regeneration, graphene has shown several promising applications. Its robust structure, electrical conductivity, and biocompatibility make it an ideal candidate for enhancing bone tissue regeneration and repair processes. Studies have revealed that the presence of graphene can stimulate the proliferation and differentiation of bone cells, thereby promoting the formation of new bone tissue. Additionally, its ability to act as an effective carrier for growth factors and drugs allows controlled release, facilitating the engineering of specific tissues for bone regeneration. Aim: To assess the efficacy of graphene in enhancing bone regeneration through in vitro studies, identify key safety concerns, and propose directions for future research to optimize its clinical applicability. Materials and methods: The present systematic review was carried out using the PRISMA 2020 guideline. A first search was carried out on 20 November 2023 and was later updated on 14 February and 15 April 2024 in the databases of PubMed, Scopus, and Web of Science. Those in vitro studies published in English that evaluated the potential for bone regeneration with graphene in dentistry and also those which met the search terms were selected. Furthermore, the quality of the studies was assessed following the modified CONSORT checklist of in vitro studies on dental materials. Results: A total of 17 in vitro studies met the inclusion criteria. Among these, 12 showed increased osteoblast adhesion, proliferation, and differentiation, along with notable enhancements in mineralized matrix formation. Additionally, they exhibited a significant upregulation of osteogenic markers such as RUNX and COL1 (p < 0.05). However, the variability in methodologies and a lack of long-term assessments were noted as critical gaps. Conclusions: The evaluation of the efficacy and safety of graphene in bone regeneration in dentistry revealed significant potential. However, it is recognized that clinical implementation should be approached with caution, considering identified areas of improvement and suggestions for future research. Future studies should focus on standardized experimental designs, including in vivo studies to evaluate long-term safety, immune responses, and vascularization processes in realistic biological environments. Full article

Background/Objectives: EnBloc resections of bone tumors of the spine are very demanding as the target to achieve a tumor-free margin specimen (sometimes impossible due to the extracompartimental tumor extension) is sometimes conflicting with the integrity of neurological functions and spine stability. Methods: The surgical treatment of a huge multi-level chordoma of the thoracic spine with unusual extension is reported. Anteriorly, the tumor widely invaded the mediastinum and displaced the aorta; on the left side, it expanded in the subpleuric region; posteriorly, it was uncommonly distant 13 mm from the posterior wall. Results: EnBloc resection is largely performed for primary bone tumors of the spine and many reports have been published concerning brilliant solutions to difficult issues of surgical anatomy. One of the major challenges is still the compatibility between oncological and functional requirements. Conclusions: Oncological staging, careful imaging analysis, a multidisciplinary surgical team, and utilization of the most recent technologies like navigation and robotics have made an oncologically appropriate EnBloc resection of a multi-level chordoma of the thoracic spine possible without affecting the continuity of the spinal canal and without any involvement of its content by an original “L”-shaped osteotomy. Full article

Background: Central venous access devices (CVADs) are crucial for various medical conditions, but pose risks, including catheter-related bloodstream infections (CRBSI). CRBSI increases comorbidity, mortality, and healthcare costs. Surveillance and evidence-based guidelines have successfully reduced CRBSI rates, although the COVID-19 pandemic has led to increased infection rates. Main body: This review explores strategies for reducing the incidence of CRBSI and examines factors contributing to variations in reported rates across developed countries. Highlighting the significant morbidity, mortality, and healthcare resource burden associated with CRBSI, the analysis delves into evidence-backed preventive measures. It discusses the impact of the COVID-19 pandemic on infection rates and proposes resilient strategies in response to these challenges. The review emphasises the importance of understanding CRBSI pathogenesis, patient, procedure, and device-related risk factors, and the implementation of evidence-guided algorithms and surveillance measures. Recommendations include the use of all-inclusive procedure packs, ultrasound-guided placement, daily dressing changes with antimicrobial treatment, and the use of antimicrobial locks. Conclusions: The review underscores the need for clear, concise algorithms adaptable to various healthcare settings and the scalability of infection prevention systems to ensure resilience. Full article

(1) Background: For the reconstruction of a human vagina, various surgical procedures are available that are often associated with complications due to their failure to mimic the physiology of the human vagina. We recently developed a vascularized, organ-specific matrix from healthy human vaginal wall tissue with suitable biomechanical properties. A superior graft would require further extensive colonization with autologous vaginal cells to reduce complications upon implantation. However, reports on isolation of vaginal cells from biopsies are scarce, and published protocols rarely contain sufficient details. In this study, we aimed to examine protocols for inconsistencies and identify (where possible) the optimal protocol in terms of reproducibility and efficiency for isolation of human vaginal fibroblasts (FBs), epithelial cells (VECs), and smooth muscle cells (SMCs). Overall, this study aims to guide other researchers and aid future tissue engineering solutions that rely on autologous cells. (2) Methods: A total of 41 isolation protocols were tested: four protocols specific to FBs, 13 protocols for VECs, and 24 protocols for SMCs. Protocols were derived from published reports on cell isolation by enzymes, with exclusion criteria including the need for specialized equipment, surgical separation of tissue layers, or missing protocol details. Enzymatic digestion with collagenase-I, collagenase-IV, and dispase-II was used for isolation of VECs, collagenase-IV for isolation of SMCs, and collagenase-IA for isolation of FBs. Fluorescent immunostaining was applied to identify VECs with cytokeratin, SMCs with desmin, endothelial cells with UEA-1, and FBs with vimentin. Protocols were assessed based on (>95%) homogeneity, duplicate consistency, cell viability, and time to first passage. (3) Results: A total of 9 out of the 41 protocols resulted in isolation and expansion of vaginal FBs. This involved 1 out of 13 VEC protocols, 6 out of 24 SMC protocols, and 2 out of 2 FB protocols. Isolation of vaginal SMCs or VECs was not achieved. The best results were obtained after digestion with 0.1% collagenase-IV, where pure FB colonies formed with high cell viability. (4) Conclusions: Today, vaginoplasty is considered the gold standard for surgically creating a neovagina, despite its considerable drawbacks and limitations. Tissue-engineered solutions carry great potential as an alternative, but cell seeding is desired to prevent complications upon implantation of grafts. In this study, we examined isolation of human vaginal FBs, SMCs, and VECs, and identified the most efficient and reliable protocol for FBs. We further identified inconsistencies and irreproducible methods for isolation of VECs and SMCs. These findings aid the clinical translation of cell-based tissue engineering for the reconstruction and support of vaginas, fulfilling unmet medic needs. Full article

Angiopoietin-1 (Ang-1) and its receptor Tie-2 promote vascular integrity and angiogenesis. MicroRNAs (miRNAs) are involved in the regulation of many cellular functions, including endothelial cell (EC) survival, proliferation, and differentiation. Several reports indicate that these effects of miRNAs on EC functions are mediated through the modulation of angiogenesis factor signaling including that of vascular endothelial growth factor (VEGF). To date, very little is known about the roles played by miRNAs in the signaling and angiogenesis promoted by the Ang-1–Tie-2 receptor axis. Our high-throughput screening of miRNAs regulated by Ang-1 exposure in human umbilical vein endothelial cells (HUVECs) has identified miR-1233-3p as a mature miRNA whose cellular levels are significantly downregulated in response to Ang-1 exposure. The expression of miR-1233-3p in these cells is also downregulated by other angiogenesis factors including VEGF, fibroblast growth factor 2 (FGF-2), transforming growth factor β (TGFβ), and angiopoietin-2 (Ang-2). The overexpression of miR-1233-3p in HUVECs using specific mimics significantly attenuated cell survival, migration, and capillary-like tube formation, and promoted apoptosis. Moreover, miR-1233-3p overexpression resulted in reversal of the anti-apoptotic, pro-migration, and pro-differentiation effects of Ang-1. Biotinylated miRNA pull-down assays showed that p53 and DNA damage-regulated 1 (PDRG1) is a direct target of miR-1233-3p in HUVECs. The exposure of HUVECs to Ang-1, angiopoietin-2 (Ang-2), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF), or transforming growth factor β (TGFβ) triggers the regulation of PDRG1 expression. This study highlights that miR-1233-3p exerts inhibitory effects on Ang-1-induced survival, migration, and the differentiation of cultured ECs. Full article

To date, therapeutic responses in plaque psoriasis are evaluated with clinical scores. No objective examination has been established. A recently developed non-invasive imaging tool, line-field confocal optical coherence tomography (LC-OCT), enables the in vivo live imaging of skin changes in psoriasis under therapy. The aim of this study was to measure therapeutic response clinically and with LC-OCT, comparing the subjectively scored epidermal changes with an AI-supported analysis. This prospective, observational study included 12 patients with psoriasis starting a systemic treatment with IL-17 inhibitors (secukinumab, ixekizumab, and bimekizumab). LC-OCT and clinical assessment with a local psoriasis and severity index of the study plaque and a control area were performed before the initiation of therapy as well as after 4 and 12 weeks of treatment. A manual and AI-supported measurement of the thickness of epidermis, stratum corneum, and undulation of the dermo-epidermal junction was carried out. Acanthosis and hyperkeratosis showed a significant reduction under treatment. AI-supported calculations were compared to subjective measurements showing good reliability with high correlation. AI-supported analysis of vascular changes may serve as a prognostic and therapeutic response marker in the future. Full article

Cancer is characterized by chronic inflammation and hypercoagulability, with an excess of venous thromboembolism (VTE). Tissue factor, the initiator of blood coagulation, circulates associated with extracellular vesicles (EV-TF). Studies investigating EV-TF between cancer-associated and non-cancer-associated VTE are lacking. We therefore compared EV-TF in unprovoked VTE (U-VTE), cancer-associated VTE (C-VTE), and cancer without VTE (C-w/o VTE). We also investigated interleukin-6 (IL-6) levels between the same groups. The final population included 68 patients (U-VTE: n = 15; C-VTE: n = 24; C-w/o VTE: n = 29). All patients with VTE were enrolled within 48 h of diagnosis; non-VTE patients were recruited in the oncologic outpatient services. EV were isolated by differential centrifugation from 4 mL of peripheral blood; the final EV pellet (16,000× g for 45 min) was resuspended in 100 μL saline and tested for TF using a one-step clotting assay. There was a statistically significant difference for higher EV-TF in C-VTE and C-w/o VTE compared to U-VTE (p = 0.024; Kruskal–Wallis test). There was no significant difference between C-VTE and C-w/o VTE. Moreover, we did not find any difference in IL-6 levels. These preliminary data suggest that cancer represents, per se, a strong driver of EV-TF generation. Full article

Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of anti-cancer treatments manifest at both cellular and tissue levels, causing deformation of cardiomyocytes, leading to contractility issues and fibrosis. Repeated irradiation and chemotherapy increase the risk of valvular, pericardial, or myocardial diseases. Multi-OMICs analyses reveal that targeting specific pathways as well as specific protein modifications, such as ubiquitination and phosphorylation, could offer potential therapeutic alternatives to current treatments, including Angiotensin converting enzymes (ACE) inhibitors and beta-blockers that mitigate symptoms but do not prevent cardiomyocyte death, highlighting the need for more effective therapies to manage cardiovascular defects in cancer survivors. This review explores the xenobiotic nature of chemotherapy agents and their impact on cardiovascular health, aiming to identify novel biomarkers and therapeutic targets to mitigate cardiotoxicity. Full article

Background and Objective: Arytenoid dislocation (AD) and subluxation (AS) impact vocal fold mobility, potentially affecting the quality of life. Their management, including the timing and modality of treatment, remains a subject of research. Our primary objective was to assess and compare the available treatment strategies for AS and AD. Material and methods: the protocol was registered on PROSPERO (CRD42023407521). Manuscripts retrieved from a previously published systematic review were evaluated. To comprehensively cover the last 25 years, an updated literature search was conducted, screening PubMed, Scopus, and Cochrane databases. Review Methods: We included studies that reported treatment modalities and the time to treatment (TT) for AS/AD, with outcomes objectively evaluated. Data on treatment success were pooled, and the impact of TT on recovery outcomes was analyzed. Results: Thirteen studies involving 361 patients were included. The majority of cases were attributed to iatrogenic trauma following intubation. Closed reduction (CR) was the primary treatment, with high success rates for both general (success rate: 77%, CI: 62–87%) and local anesthesia (success rate: 89%, CI: 70–97%). The standardized mean difference for the TT effect on treatment outcome was −1.24 (CI: −2.20 to −0.29). Conclusions: The absence of randomized controlled trials and the overall moderate-to-low quality of the studies highlighted the importance of the finding’s careful interpretation. This meta-analysis underscores the effectiveness of CR in managing AS/AD, with both general and local anesthesia yielding high success rates. The findings highlight the importance of TT, suggesting that early intervention is paramount. Future clinical research is needed to further refine these findings and optimize treatment protocols. Full article

Background/Objective: The blood–brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood. This study aimed to characterize the time-dependent changes in BBB permeability, transporter function, and inflammatory responses in both sonicated and non-sonicated brain tissues following LiFUS treatment. Methods: We employed in situ brain perfusion to assess alterations in BBB integrity and transporter function, as well as multiplex cytokine analysis to quantify the inflammatory response. Results: Our findings show that LiFUS significantly increased vascular volume and glucose uptake, with reduced P-gp function in brain tissues six hours post treatment, indicating biphasic BBB disruption. Additionally, elevated levels of pro-inflammatory cytokines, including TNF-α and IL-6, were observed in both sonicated and non-sonicated regions. A comparative analysis between wild-type and immunodeficient mice revealed distinct patterns of cytokine release, with immunodeficient mice showing lower serum concentrations of IFN-γ and TNF-α, highlighting the potential impact of immune status on the inflammatory response to LiFUS. Conclusions: This study provides new insights into the biphasic nature of LiFUS-induced BBB disruption, emphasizing the importance of understanding the timing and extent of secondary physiological changes. Full article

Introduction: Basal cell carcinoma (BCC) is the most prevalent type of skin cancer worldwide. Despite its low metastatic potential, certain subtypes present an aggressive clinical course. Part II focuses on the different dermoscopic patterns observed in BCC, depending on the lesion subtype, its location on the body, the patient’s age, the size of the tumor, and skin phototype. Methods: A search of the PubMed database was conducted for studies reporting dermoscopic findings in BCC across all body locations, histopathologic subtypes, tumor sizes, ages of onset and skin phototypes. Results: There are no dermoscopic features indicative of a particular BCC subtype. However, arborizing, truncated or glomerular vessels, shiny white lines, ulceration, white areas, absence of pink zones and large blue-gray ovoid nests suggest high-risk BCCs (morpheaform, micronodular, infiltrative, basosquamous). Pigmented features can occur in all BCC types, though increased pigmentation indicates less aggressive subtypes (nodular, superficial, fibroepithelioma of Pinkus, adenoid). BCCs most commonly develop on the head, typically presenting as nodular and non-pigmented tumors. Those on the nose, eyes and ears may be more aggressive and prone to recurrence. On the trunk, BCCs are usually superficial and pigmented. Lower limb lesions often show polymorphous vessels rather than arborizing ones, which makes the dermoscopic diagnosis challenging. Dermoscopy aids early detection, with larger tumors exhibiting more established features but no size-specific patterns. Aggressive subtypes display similar dermoscopic findings regardless of size. Conclusions: Dermoscopy is a valuable tool for the early detection of BCC, though no specific dermoscopic features can definitively identify subtypes. High-risk BCCs can be suspected when distinct vascular and structural patterns are present, particularly in lesions located on the face, especially around the nose, eyes and ears, while pigmented features may indicate less aggressive subtypes. Full article

Background: Traditional root canal therapy (RCT) effectively removes diseased or necrotic pulp tissue and replaces it with inorganic materials. Regenerative endodontics is an alternative to conventional RCT by using biologically based approaches to restore the pulp–dentin complex. This review explores emerging techniques, including autogenic and allogenic pulp transplantation, platelet-rich fibrin, human amniotic membrane scaffolds, specialized pro-resolving mediators, nanofibrous and bioceramic scaffolds, injectable hydrogels, dentin matrix proteins, and cell-homing strategies. These methods utilize stem cells, growth factors, and biomaterials to regenerate vascularized, functional pulp tissue. Methods: A narrative review was conducted using PubMed, Scopus, and Embase to identify studies published between 2010 and 2023. In vitro, animal, and clinical studies focusing on innovative regenerative endodontic techniques were analyzed. Conclusions: Although regenerative endodontics demonstrates great potential, challenges remain in standardizing protocols, addressing biological variability, and achieving consistent clinical outcomes. Future research must focus on refining these techniques to ensure their safety, efficacy, and accessibility in routine practice. By addressing current limitations, regenerative endodontics could redefine the management of pulpitis, offering biologically based treatments that enhance tooth vitality, structural integrity, and long-term prognosis. Full article

Background/Objectives: Despite advances in diagnostic techniques, accurate classification of lung cancer subtypes remains crucial for treatment planning. Traditional methods like genomic studies face limitations such as high cost and complexity. This study investigates whether integrating atomic force microscopy (AFM) measurements with conventional clinical and histopathological data can improve lung cancer subtype classification. Methods: We developed and analyzed a novel dataset combining clinical, histopathological, and AFM-derived biophysical characteristics from 37 lung cancer patients. Various machine learning techniques were evaluated, with a focus on Bayesian Networks due to their ability to handle complex data with missing values. Leave-One-Out Cross-Validation was employed to assess model performance. Results: The integration of biophysical features improved classification accuracy from 86.49% to 89.19% using a data-driven Bayesian Network model, though this improvement was not statistically significant (p = 1.0). Four key features were identified as highly predictive: sex, vascular invasion, perineural invasion, and ALK mutation. A simplified model using only these features achieved identical performance with significantly reduced complexity (BIC 51.931 vs. 268.586). Conclusions: While AFM-derived measurements showed promise for enhancing lung cancer subtype classification, larger datasets are needed to fully validate their impact. Our findings demonstrate the feasibility of incorporating biophysical measurements into cancer classification frameworks and identify the most predictive features for accurate diagnosis. Further research with expanded datasets is needed to validate these findings. Full article

Background/Objectives: Both hyperandrogenism (HA) and vitamin D deficiency (VDD) can separately lead to impaired vascular reactivity and ovulatory dysfunction in fertile females. The aim was to examine the early interactions of these states in a rat model of PCOS. Methods: Four-week-old adolescent female rats were divided into four groups: vitamin D (VD)-supplemented (n = 12); VD-supplemented and testosterone-treated (n = 12); VDD- (n = 11) and VDD-and-testosterone-treated (n = 11). Animals underwent transdermal testosterone treatment for 8 weeks. Target VD levels were achieved with oral VD supplementation and a VD-free diet. Estrous cycles were followed by vaginal smear, and quantitative histomorphometric measurements of the ovaries were also taken. In the 8th week, testosterone- and estrogen-induced relaxation of coronary arterioles was examined with pressure angiography. Estrogen receptor (ER) density and oxidative and nitrative stress parameters (Poly-(ADP-Ribose)-Polymerase and 3-nitrotyrosine) in the vessel wall were investigated with immunohistochemistry. Results: VDD caused impaired estrous cycles, and testosterone caused anovulatory cycles (the cycles were stopped at the diestrous phase). VDD combined with testosterone treatment resulted in reduced testosterone and estrogen vasorelaxation, lower ER density, and higher oxidative and nitrative stress in the vessel wall. Conclusions: PCOS with vitamin D deficiency may be associated with increased oxidative–nitrative stress in coronary arterioles. This oxidative and nitrative stress, potentially caused by hyperandrogenism and/or vitamin D deficiency, could impair estrogen-induced relaxation of the coronary arterioles, possibly by decreasing NO bioavailability and disrupting the estrogen-induced relaxation pathway. Full article