Search Results (69,542)

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

Objective: To evaluate the efficacy of NADPH oxidase 4 and miR-146a-5p in current treatment planning for ascending aortic aneurysms, independent of aortic diameter, and to develop protocols that will ensure the treatment of ascending aortic aneurysms, which pose a risk for aortic dissection, without complications. Methods: Patients who met the inclusion criteria and underwent surgery at Dr. Siyami Ersek Chest, Heart, and Vascular Surgery Training and Research Hospital for ascending aortic aneurysms and coronary artery disease between 2023 and 2024 were included in the study. This study was designed as a prospective study. Demographic, biochemical, radiological, and echocardiographic data were collected, and NOX4 mRNA and miR-146a-5p expressions were examined and compared in tissue samples. Results: The study was conducted on a total of 50 patients, with 25 patients in the aneurysm group and 25 patients in the control group. miR-146a-5p expression levels were found to be significantly decreased in the patient group compared to the control group (p = 0.001). When NOX4 mRNA expression levels were examined, no significant difference was found between the control and aneurysm groups. No correlation was found between NOX4 mRNA and miR-146a-5p levels (p = 0.764). When the relationship between ascending aorta diameter and both NOX4 mRNA and miR-146a-5p was examined, it was found that miR-146a-5p expression was negatively correlated with ascending aorta diameter (p = 0.036) and did not show a significant correlation with NOX4 mRNA levels (p = 0.318). A similar correlation was also found with ascending aorta length. The correlation of NOX4 mRNA and miR-146a-5p expression levels with age, gender, and ejection fraction was investigated separately. No significant correlation was found for all three variables. The optimum cut-off value to be used to separate the patient group from the control group using miR-146a-5p expression levels, as well as the sensitivity and specificity of miR-146a-5p expression levels when this cut-off value was used, was calculated using an ROC curve. Specificity for miR-146a-5p expression was found to be 88%, and sensitivity was found to be 66%. Conclusions: The study found promising results indicating that NOX4, shown to be a determinant of vascular oxidative stress, is not involved in the development of ascending aortic aneurysms; however, miR-146a-5p, which functions in the regulation of many inflammatory responses, including the regulation of NOX4 expression, may help prevent the development of ascending aortic aneurysms. Further studies aimed at elucidating the genetic and biochemical processes involved in aneurysm development suggest that miR-146a-5p could be a therapeutic target for preventing aneurysms. Full article

Background: Breast clip marker movement after ultrasound-guided biopsy can negatively affect lesion re-localisation rates and surgical outcomes, underscoring the need for improved understanding of the factors influencing clip displacement. Thus, this study aimed to compare four different breast clip markers and identify risk factors for clip migration and dislocation after ultrasound-guided placement. Methods: This retrospective study included 350 patients who underwent ultrasound-guided biopsy of a newly diagnosed breast lesion with placement of one of four types of breast clips (UltraClip Dual Trigger Biodur 108 Coil Marker [UC], TUMARK Professional [TP], TUMARK Vision [TV] and HydroMARK Breast Biopsy Site Marker [HM]). Clip migration and dislocation were assessed immediately after placement and during follow-up imaging for at least 3 months. A binary logistic regression analysis was performed to identify predictors of clip dislocation including lesional, perilesional and procedural parameters. Results: Clip migration rates were 26.0%, 18.0%, 10.0% and 25.0% and clip dislocation rates were 14.0%, 20.0%, 9.0% and 38.0% for UC, TP, TV and HM, respectively. Features significantly associated with clip dislocation included predominantly fatty surrounding tissue (p = 0.046) with low perilesional shear wave velocities (p = 0.054), smooth lesion contours (p = 0.041), soft lesion strain elastography (p =0.001), low clip-to-lesion-surface distance (p = 0.002) and the use of an HM breast clip (p = 0.032). Conclusions: The type of breast clip-marker, as well as perilesional and lesional characteristics, influence the likelihood of clip dislocation. Notably, the hydrogel-coated clip (HM) exhibited the highest rate of dislocation. Full article

A fraction of the insulin-stimulated uptake of long-chain fatty acids (FAs) is mediated by the FA translocase cluster of differentiation 36 (CD36) in white adipocytes. Intracellular vesicle-localized CD36 is redistributed to the plasma membrane following insulin stimulation, enhancing the uptake of long-chain FAs across the plasma membrane. We previously developed an epitope-tagged CD36 reporter, which enabled the visualization and quantification of the plasma membrane translocation of CD36. Herein, we demonstrate that the insulin-stimulated CD36 translocation is regulated by the phosphoinositide 3-kinase (PI3K)/Akt2/Rac1/RalA axis in adipocytes of subcutaneous white adipose tissue (WAT) in living mice. The uptake of long-chain FAs by insulin was completely abrogated in white adipocytes isolated from adipocyte-specific rac1-knockout (adipo-rac1-KO) mice. Correspondingly, the translocation of CD36 to the plasma membrane by insulin was also totally inhibited in Rac1-deficient white adipocytes. PI3K and Akt2 acted upstream of Rac1, and the guanin nucleotide exchange factor FLJ00068 served as a regulator for Rac1. Furthermore, the involvement of another small GTPase RalA was suggested by inhibitory effects of a dominant-negative mutant. Taken together, these results support the notion that insulin regulates the plasma membrane translocation of CD36 by mechanisms similar to those for the translocation of the glucose transporter GLUT4 in white adipocytes. Full article

The NaI(TI) detector is highly favored in gamma radiation detection and widely applied in fields such as environmental radiation monitoring, nuclear medicine, and laboratory gamma-ray spectroscopy. Its detection performance determines the results of quantitative gamma-ray detection, making it a crucial indicator in detector design and development. This study employs the Monte Carlo method and utilizes TopMC 1.0 software to establish a NaI(TI) detector model. First, the effects of crystal size, ray energy, cladding thickness, and distance on the detector’s detection efficiency were investigated. Subsequently, the energy resolution and peak-to-total ratio of the detector were simulated and calculated, with comparisons made to experimental values. The results indicate that all three detection efficiencies of the NaI(TI) detector are positively correlated with crystal size and exhibit an initial increase followed by a decrease with rising gamma-ray energy. Both the absolute detection efficiency and full-energy peak detection efficiency first increase and then decrease with increasing cladding thickness, while showing a negative correlation with detection distance. The intrinsic detection efficiency is almost unaffected by cladding thickness and initially rises before declining with increasing detection distance. The simulated values of energy resolution closely match experimental values, improving with higher gamma-ray energy. The deviation between simulated and experimental values for different source peak-to-total ratios remains within 6.25%, verifying the model’s reliability and the accuracy of simulation data. These findings provide valuable references and guidance for optimizing detection performance, conducting source-free efficiency calibration, and structural design of NaI(TI) detectors. Full article

Accurate assessment of carbon storage dynamics and their driving factors is important for ecological sustainability and land management on the Loess Plateau under China’s dual carbon goals. In this study, the InVEST and PLUS models were integrated to evaluate carbon storage changes from 2000 to 2020 and simulate future carbon storage patterns for 2030 under four development scenarios, including natural development (ND), rapid development (RD), cropland protection (CP), and ecological protection (EP). In addition, the XGBoost-SHAP framework was employed to identify the dominant drivers and nonlinear response relationships controlling spatial variation in carbon storage. During 2000–2020, ecosystem carbon storage across the Loess Plateau generally increased, rising from 5.780 Pg to 5.893 Pg. Spatially, carbon storage displayed a pronounced pattern characterized by higher levels in the southeast and lower levels in the northwest, aligning with forest–grassland restoration belts. Scenario simulations showed that EP produced the largest carbon storage gain, with total carbon storage projected to reach 5.962 Pg in 2030. In contrast, RD reduced carbon storage to 5.858 Pg because of intensive construction land expansion. XGBoost-SHAP results identified net primary productivity (NPP) as the most influential factor controlling spatial variation in carbon storage, accounting for 57.3% of the total explanatory importance, whereas soil erosion (SE) exhibited a strong negative effect on carbon storage. Population density (POPD) also exerted a negative effect, whereas gross domestic product (GDP) showed positive contributions in economically developed counties. These findings enhance understanding of the spatial response characteristics of carbon storage under environmental gradients and human disturbance across the Loess Plateau. They further provide scientific support for differentiated ecological management and regionally adapted carbon mitigation planning. Full article

Background: Infectious diseases remain a leading cause of mortality in South Africa, compounded by a high HIV prevalence. This study aimed to delineate the spectrum and clinicopathological characteristics of fatal infectious diseases through a postmortem audit to inform clinical practice and public health strategy. Methods: A retrospective, cross-sectional descriptive study was conducted on all autopsies with a final cause of death attributed to infectious disease at a National Health Laboratory Service, in Northern Pretoria, Gauteng, South Africa, from 2012 to 2021. Using the Systematised Nomenclature of Medicine Clinical Terms (SNOMED) code and word search engines codes, 55 cases were identified. Data on demographics, clinical presentation, HIV status, antiretroviral therapy (ART), comorbidities, and final autopsy diagnosis were extracted from the laboratory information system. Histological confirmation was performed using standard stains. Descriptive statistical analysis was conducted using STATA-18. Results: The cohort (n = 55) had a median age of 31 years (IQR 19–45) and was predominantly female (67%). HIV prevalence was 35%, with 68% of those on ART. The leading cause of death was multilobar pneumonia (36%), followed by bronchopneumonia (22%). AIDS-defining illnesses were present in 27% of cases, with disseminated tuberculosis being the most common (46%). Septic shock was identified in 18% of decedents. A significant proportion (60%) of the cohort was HIV-negative. Conclusions: This autopsy series reveals a high burden of fatal community-acquired pneumonias and HIV-associated opportunistic infections, with a notable proportion of deaths occurring in HIV-negative individuals. The findings underscore diagnostic gaps and highlight the critical role of autopsy in accurate mortality surveillance, advocating for enhanced antemortem diagnostic protocols and targeted public health interventions. Full article

Background: The tumor immune microenvironment, particularly the role of cytotoxic CD8+ T lymphocytes, is crucial in cancer progression but remains poorly understood in pituitary neuroendocrine tumors (PitNETs). The significance of CD8+ cell infiltration varies across PitNET subtypes, suggesting a complex interplay with tumor cell lineage. This study aimed to characterize the distribution of CD8+ tumor-infiltrating lymphocytes across different PitNET subtypes defined by the current WHO classification and to explore their association with clinicopathological features. Methods: We conducted a retrospective study on 40 surgically resected PitNETs. All cases were classified based on immunohistochemical expression of pituitary hormones and lineage-specific transcription factors (PIT-1, TPIT, SF-1). CD8+ lymphocyte density was quantified using immunohistochemistry and calculated as cells/mm². Exploratory statistical analysis was performed based on non-parametric tests to compare CD8+ cell density across tumor subtypes and with parameters like tumor size, invasiveness (Knosp grade), and proliferation index (Ki-67). Findings are to be treated as observational trends. Results: The highest density of CD8+ lymphocytes was observed in plurihormonal PIT-1-positive tumors [17.61 cells/mm² (IQR: 17.61–60.36)], followed by somatotroph [13.2 (6.6–15.72)] and mammosomatotroph [13.83 (0–21.38)] tumors. A difference in CD8+ density was found between PIT-1-positive and PIT-1-negative tumors (n1 = 34, n2 = 6, U = 49.5, p_exact = 0.050, r = 0.33); the medium effect size indicates a possible lineage-related trend. Another difference was observed between SF-1-positive and SF-1-negative tumors (p = 0.025), with SF-1 lineage tumors showing the lowest infiltration. No correlations were found between CD8+ density and tumor size, Knosp grade, or Ki-67 index. Conclusions: The distribution of intratumoral CD8+ T lymphocytes in PitNETs is highly heterogeneous and appears to be strongly dictated by the transcription factor-defined tumor lineage rather than by traditional clinicopathological markers of aggressiveness. PIT-1 lineage tumors harbor a more active immune microenvironment, while SF-1 lineage tumors are relatively ‘immune-poor’. These findings highlight the immunological diversity of PitNETs and support further investigation of the tumor immune landscape. Collaborative multi-institutional studies are required to validate these trends. Full article

This study examines whether environmental, social, and governance (ESG) performance reduces credit risk in Gulf Cooperation Council (GCC) banks over 2014–2025, and whether this relationship differs between Islamic and conventional banks. Using loan-loss provision (LLP) ratios as the primary credit risk proxy, we estimate two-way fixed-effects panel regressions and, as the primary specification, a two-step System GMM estimator for 43 banks across six GCC countries (258 bank-year observations). Our results are threefold. First, accounting for profit persistence and endogenous capital accumulation through System GMM reveals a significant negative aggregate ESG–credit risk relationship absent from static fixed-effects estimates, directly supporting the credit risk reduction hypothesis. Second, pillar decomposition identifies the social score as the primary driver, while governance and environmental scores are individually insignificant in the full sample. Third, split-sample GMM estimates reveal that Islamic bank credit risk dynamics are structurally distinct: profitability (ROA) suppresses provisioning approximately 1.2 times more powerfully than in conventional banks, loan intensity disciplines rather than amplifies credit risk under Sharia asset-backed financing, and lagged provisioning exhibits a mean-reversion pattern unique to the profit-and-loss sharing model. Full article

Background/Objectives: Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity, and the relationship between labour-induction duration and haemorrhagic risk has not been translated into a practical intrapartum risk-stratification framework. We aimed to derive a clinically interpretable induction-duration threshold for PPH risk stratification and to explore an internally validated parsimonious clinical decision-support model. Methods: In this retrospective cohort of 1128 induced singleton labours at ≥37 weeks at a Turkish tertiary centre, laboratory-defined PPH was operationalised as a haemoglobin drop ≥ 2 g/dL. Multivariable logistic regression identified independent predictors; receiver operating characteristic (ROC) analysis with 2000-replicate bootstrap internal validation derived a duration threshold; calibration, decision curve analysis, and a probability-scaled nomogram were additionally evaluated. Results: PPH occurred in 143 patients (12.7%). Four predictors were independently associated with PPH: induction duration (adjusted odds ratio 1.243 per hour; 95% CI 1.191–1.298; p < 0.001), parity, emergency caesarean, and maternal age. Induction duration achieved an apparent area under the curve of 0.773 (optimism-corrected 0.773); a Youden-optimal threshold of 10.1 h yielded 86.7% (95% CI 80.2–91.3%) sensitivity and 96.8% (95% CI 95.0–97.9%) negative predictive value. The model showed favourable calibration and positive net clinical benefit on decision curve analysis. Conclusions: Induction duration was independently associated with PPH; the internally validated 10.1 h threshold therefore represents a hypothesis-generating risk-stratification benchmark—reflecting an association rather than a demonstrated causal effect—that requires prospective external validation in independent populations before clinical application. Whether this association is causal or reflects an underlying myometrial phenotype requires prospective study. Full article

Background/Objectives: Differentiating recurrent disease from postsurgical changes on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) remains challenging in malignant pleural mesothelioma (MPM). This study aimed to characterize the temporal patterns of postsurgical FDG uptake and evaluate the diagnostic performance of FDG PET/CT for detecting recurrent disease after radical surgery. Methods: We retrospectively analyzed 91 postsurgical PET/CT scans from 45 patients with MPM who underwent extrapleural pneumonectomy (EPP; n = 29) or pleurectomy/decortication (P/D; n = 16). Scans were stratified into four postoperative time intervals: <6 months, 6 to <12 months, 12 to <24 months, and ≥24 months. FDG uptake in the postsurgical bed and local recurrent lesions was quantified using maximum standardized uptake value ratios normalized to the mediastinal blood pool and liver. Recurrence was confirmed by histopathology or follow-up imaging. Results: Postsurgical FDG uptake showed a time-dependent decline, with significantly lower uptake beyond 24 months postoperatively (p < 0.05). EPP patients demonstrated significantly higher postsurgical FDG uptake than P/D patients (p < 0.01). FDG PET/CT identified occult recurrence in 23.4% of CT-negative scans. Local recurrent lesions showed significantly higher FDG uptake than postsurgical changes across all postoperative intervals (p < 0.001). Conclusions: Postsurgical FDG uptake in MPM demonstrates a time-dependent decline, and surgical extent is an important determinant of background metabolic activity. Despite this variable background, FDG PET/CT demonstrated high diagnostic accuracy for detecting recurrent disease, including CT-occult recurrences. Incorporating surgical type and postoperative interval into PET/CT interpretation may improve diagnostic accuracy in postoperative MPM surveillance. Full article

Surge reliability is a crucial aspect of silicon carbide (SiC) metal-oxide-semiconductor field-effect transistor (MOSFET) reliability. This study investigates the degradation behavior and mechanisms of switching characteristics in 1.2 kV planar-gate SiC MOSFETs under repetitive surge current. A surge current test platform is established to conduct surge tests on the device, while monitoring the evolution of its switching characteristics. The results indicate that after 4000 surge current cycles, the device’s turn-on delay time (t_d(on)), rise time (t_r), and turn-on loss (E_ON) show no significant changes. In contrast, the turn-off delay time (t_d(off)), fall time (t_f), and turn-off loss (E_OFF) increase by 9%, 7.5%, and 8.3%, respectively. Switching characteristics variations are closely linked to the reduction in threshold voltage (V_TH) and the increase in gate-source capacitance (C_GS) and gate-drain capacitance (C_GD). The degradation of these parameters stems from the accumulation of positive trapped charge in the gate oxide layer above the channel and junction field-effect transistor (JFET) region. The increase in charges results from the combined effects of negative gate bias and cyclic high temperature induced by repetitive surge current. This study provides a theoretical basis for the comprehensive understanding of the impact of surge current on SiC MOSFET performance. Full article

Although generative artificial intelligence (AI) has increasingly been used to create destination marketing images, tourists’ responses to such images remain unclear. Prior research has often attributed negative reactions to the visual characteristics of AI-generated images. However, limited attention has been paid to how tourists interpret these images within broader cultural contexts. Drawing on authenticity theory and cultural learning theory, this research examines the effect of image type (AI vs. human) on tourists’ perceived authenticity and visit intention, as well as the moderating roles of cultural learning cues in this process. Using three experiments, the results show that AI-generated images reduce perceived authenticity and visit intention compared with images taken by humans. Notably, while salient cultural learning cues enhance tourists’ perceived authenticity and visit intentions, different types of cues produce distinct outcomes: commodified cultural cues mitigate tourists’ negative responses to AI-generated images, whereas heritage cultural cues amplify authenticity concerns. These findings provide strategic insights for destination marketers on how to deploy AI-generated images effectively in tourism destination marketing. Full article

Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only target isolated aspects of wound healing and fail to address the complex, interdependent pathophysiology of chronic wounds, particularly tissue hypoxia, edema, impaired microcirculation, and persistent inflammation. Cyclical Pressurized Topical Wound Oxygen (TWO₂) therapy is a home-based, multimodal intervention that combines humidified topical oxygen delivery with cyclical non-contact compression to address these core drivers simultaneously. Methods: This review synthesizes mechanistic rationale and evidence from randomized controlled trials, long-term venous ulcer studies, and real-world comparative effectiveness analyses. Emphasis is placed on the large cohort study by Yellin et al., which directly compared TWO₂ with other advanced modalities including negative pressure wound therapy (NPWT), skin substitutes, and growth factor therapies. Results: Across these studies, TWO₂ therapy is consistently associated with improved healing durability, reduced recurrence, and substantial reductions in hospitalization and amputation rates compared with both standard care and advanced wound therapies. Conclusions: The convergence of randomized and real-world evidence supports TWO₂ therapy as a clinically meaningful and mechanism-driven adjunctive treatment option for patients with chronic, high-risk lower-extremity wounds. Full article

Background/Objectives: Optical coherence tomography (OCT) and OCT angiography (OCT-A) provide detailed measurements of retinal structure and vasculature; however, age-related differences in how these parameters correlate with one another remain poorly understood. We hypothesized that vascular–structural integration in the macula is more pronounced in adults than in children. Our aim was to characterize correlation patterns in pediatric and adult populations to inform the development of age-specific clinical interpretation guidelines. Methods: This prospective cross-sectional observational study enrolled 37 healthy children (age 1–17 years) and 28 healthy adults (age 18–65 years). Eyes with ocular or systemic conditions affecting the retina or prior intraocular surgery were excluded. Standardized OCT and OCT-A acquisition protocols provided structural and vascular measures. Univariable correlation analyses applied a stringent threshold (p < 0.001) to identify robust associations. Significant univariable results were entered into multivariable regression models adjusting for age, gender, intraocular pressure, and axial length. A Group-wise Linkage Proportion quantified the percentage of potential significant correlations among eight predefined anatomical parameter groups. Results: Ninety univariable correlations met p < 0.001. Fourteen correlations were shared across age groups, notably foveal avascular zone metrics and vessel density, showing very large negative correlations (r = −0.70 to −0.87). The pediatric cohort displayed 40 unique correlations, primarily linking optic nerve head flow indices to retinal nerve fiber layer thickness. Adults exhibited 36 unique correlations, dominated by macular vascular–thickness coupling concentrated in the parafoveal region. After multivariable adjustment, 52 of 90 associations remained significant. Adult-specific associations lost significance more frequently (58%) than pediatric-specific associations (43%), whereas correlations shared across both groups showed complete stability (100%). The Group-wise Linkage Proportion indicated pronounced macular vascular–structural coupling in adults (48.4%) versus near absence in children (1.2%). Conclusions: Retinal parameter correlation patterns show fundamental differences between pediatric and adult eyes. While optic nerve head-macular thickness relationships remain consistent across ages, adults exhibit mature, localized integration of macular vascular and structural parameters absent in children. These findings suggest that pediatric and adult OCT/OCT-A measurements may benefit from separate reference standards, although prospective validation is required before clinical implementation. Full article