Search Results (258)

Objective: Nimodipine still represents a unique selling point in the prevention of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Its intrathecal effect is limited by a low oral bioavailability, leading to the development of nanocarrier systems to overcome this limitation. This study investigated the ultrasound-induced release profile of nimodipine from drug-loaded copolymers in artificial cerebrospinal fluid (CSF) within 72 h after a singular versus repeated sonication. Methods: Pluronic^® F127 copolymers (Sigma-Aldrich, Taufkirchen, Germany)were loaded with nimodipine by direct dissolution. Spontaneous and on-demand drug release by ultrasound (1 MHz at 1.7 W/cm²) was determined in artificial cerebrospinal fluid using the dialysis bag method. Nimodipine concentrations were measured at predefined time points within 72 h of sonication. Results: Spontaneous release of nimodipine was enhanced by ultrasound application with significantly increased nimodipine concentrations two hours after a repeated sonication compared to a singular sonication (median 1.62 vs. 17.48 µg/µL, p = 0.04). A further trend was observed after four hours (median 1.82 vs. 22.09 µg/µL, p = 0.06). There was no difference in the overall nimodipine concentrations between the groups with a singular versus repeated sonication (357.2 vs. 540.3 µg/µL, p = 0.60) after 72 h. Conclusions: Repeated sonication resulted in an acceleration of nimodipine release from the drug-loaded copolymer in a CSF medium. These findings confirm the proof of principle of an on-demand guidance of nimodipine release from nimodipine-loaded nanodrugs by means of ultrasound, which suggests that evaluating the concept in an animal model may be appropriate. Full article

Background and Objectives: The threshold for ineffective esophageal motility (IEM) diagnosis was changed in Chicago v4.0. Our aim was to determine IEM prevalence using the new criteria and the differences between patients with definite IEM versus “inconclusive diagnosis”. Materials and Methods: We retrospectively selected IEM and fragmented peristalsis (FP) patients from the high-resolution esophageal manometries (HREMs) database. Clinical, demographic data and manometric parameters were recorded. Results: Of 348 HREMs analyzed using Chicago v3.0, 12.3% of patients had IEM and 0.86% had FP. Using Chicago v4.0, 8.9% of patients had IEM (IEM-4 group). We compared them with the remaining 16 with an inconclusive diagnosis of IEM (borderline group). Dysphagia (77% vs. 44%, Z-test = 2.3, p = 0.02) and weight loss were more commonly observed in IEM-4 compared to the borderline group. The reflux symptoms were more prevalent in the borderline group (87.5% vs. 70.9%, p = 0.2). Type 2 or 3 esophagogastric junction morphology was more prevalent in the borderline group (81.2%) vs. 64.5% in IEM-4 (p = 0.23). Distal contractile integral (DCI) was lower in IEM-4 vs. the borderline group, and resting lower esophageal sphincter (LES) pressure and mean integrated relaxation pressure (IRP) were similar. The number of ineffective swallows and failed swallows was higher in IEM-4 compared to the borderline group. Conclusions: Using Chicago v4.0, less than 10% of patients had a definite diagnosis of IEM. The dominant symptom was dysphagia. Only DCI and the number of failed and inefficient swallows were different between definite IEM patients and borderline cases. Full article

This study investigated the potential of phosphodiesterase type 5 (PDE-5) inhibitors, specifically tadalafil, in preventing the delayed cerebral ischemia (DCI) post-rupture of cerebral aneurysms. A total of 19 rabbits were used in this study, divided into different treatment groups, including nimodipine alone, tadalafil alone, and a combination of nimodipine and tadalafil. Both nimodipine and tadalafil showed some impact on reducing endothelial apoptosis in the basilar arteries, although the effects were not statistically significant. Notably, the nimodipine group exhibited significantly lower levels of Bax in the small arterioles compared to the SAH group. These findings suggest that while tadalafil may not directly prevent endothelial cell death like nimodipine, its neuroprotective properties hint at its potential utility in DCI treatment. Further research involving a broader range of apoptosis-related proteins is recommended to enhance our understanding in this area. Full article

The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher’s exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer. Full article

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70–140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier. Full article

Eukaryotic genomes are organized into chromatin domains through long-range chromatin interactions which are mediated by the binding of architectural proteins, such as CTCF and cohesin, and histone modifications. Based on the published Hi-C and ChIP-seq datasets in human monocyte-derived macrophages, we identified 206 and 127 differential chromatin interactions (DCIs) that were not located within transcription readthrough regions in influenza A virus- and interferon β-treated cells, respectively, and found that the binding positions of CTCF and RAD21 within more than half of the DCI sites did not change. However, five histone modifications, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3, showed significantly more dramatic changes than CTCF and RAD21 within the DCI sites. For H3K4me3, H3K27ac, H3K36me3, and H3K27me3, significantly more dramatic changes were observed outside than within the DCI sites. We further applied a motif scanning approach to discover proteins that might correlate with changes in histone modifications and chromatin interactions and found that PRDM9, ZNF384, and STAT2 frequently bound to DNA sequences corresponding to 1 kb genomic intervals with gains or losses of a histone modification within the DCI sites. This study explores the dynamic regulation of chromatin interactions and extends the current knowledge of the relationship between histone modifications and chromatin interactions. Full article

Electric vehicles are considered by many as an emission-free or low-emission solution to meet the challenge of sustainable transportation. However, the operational input, electrical energy, has an associated cost, greenhouse gasses, which results in indirect emissions. Given this knowledge, we pose the following question: “Are zero-emission transportation targets achievable given our current energy mix?” The objective of this article is to assess the impact of a grid’s energy mix on the indirect emissions of an electric vehicle. The study considers real-world data, vehicle usage data from an electric vehicle, and carbon intensity data for India, the USA, France, the Netherlands, Brazil, Germany, and Poland. Linear programming-based optimization is used to compute the best charging scenario for each of the given grids and, consequently, the indirect emissions are compared to those of a high-efficiency 1.5 L diesel internal combustion engine for the vehicle: a 2019 Renault Clio dCi 85. The results indicate that for grids with low renewable energy penetration, such as those of Poland and India (Maharashtra), an electric vehicle, even when optimally charged, can be classified as neither a low- nor zero-emission alternative to normal thermal vehicles. Also, for grids with elevated levels of variation in their carbon intensity, there is significant potential to reduce the carbon footprint related to charging an electric vehicle. This article provides a real-world perspective of how an electric vehicle performs in the face of different energy mixes and serves as a precursor to the development of robust indicators for determining the carbon reductions related to the e-mobility transition. Full article

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC. Full article

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series. Full article

Patent foramen ovale (PFO) is a remnant of the foetal circulation resulting from incomplete occlusion of the septum primum and septum secundum. Although prevalent in about 25% of the population, it mainly remains asymptomatic. However, its clinical significance in situations such as cryptogenic stroke, migraine, and decompression illness (DCI) has been well described. Recent randomised clinical trials (RCTs) have demonstrated the efficacy of percutaneous PFO closure over pharmacological therapy alone for secondary stroke prevention in carefully selected patients. Notably, these trials have excluded older patients or those with concurrent thrombophilia. Furthermore, the role of closure in other clinical conditions associated with PFO, like decompression sickness (DCS) and migraines, remains under investigation. Our review aims to summarise the existing literature regarding epidemiology, pathophysiological mechanisms, optimal management, and closure indications for these special patient groups. Full article

The acquisition of digital images is susceptible to haze, and images captured under such adverse conditions may impact high-level applications designed for clean input data. Image dehazing emerges as a practical solution to this problem, as it can be employed to pre-process images immediately after acquisition. This paper presents a concise review of impactful algorithms, including those based on deep learning models, to identify the existing gap in real-time processing capabilities. Subsequently, a real-time dehazing system on a multiprocessor system-on-a-chip (MPSoC) platform is introduced to bridge this gap. The proposed system balances the trade-off between dehazing performance and computational complexity; hence, the name “Symmetric” is coined. Additionally, the entire system is implemented in programmable logic and wrapped by an interface circuit supporting double-buffering, rendering it highly suitable for seamless integration into existing camera systems. Implementation results on a Zynq UltraScale+ MPSoC ZCU106 Evaluation Kit demonstrate a maximum operating frequency of 356.51 MHz, equivalent to a maximum processing speed of 40.27 frames per second for DCI 4K resolution. Full article

The aim of this study was to compare the characteristics of breast microcalcification on digital mammography (DM) with the histological and molecular subtypes of breast cancer and to identify the predictive value of DM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing microcalcifications for radiologic–pathologic correlation. We relied on our prospectively maintained database of suspicious microcalcifications on DM, from which data were retrospectively collected between January 2020 and April 2023. We enrolled 158 patients, all of whom were subjected to biopsy. Additionally, 63 patients underwent breast DCE-MRI. Microcalcifications with a linear branched morphology were correlated with malignancies (p < 0.001), among which an association was highlighted between triple negatives (TNs) and segmental distribution (p < 0.001). Amorphous calcifications were correlated with atypical ductal hyperplasia (ADH) (p = 0.013), coarse heterogeneous (p < 0.001), and fine-pleomorphic (p = 0.008) with atypical lobular hyperplasia (ALH) and fine pleomorphic (p = 0.009) with flat epithelial atypia (FEA). Regarding DCE-MRI, no statistical significance was observed between non-mass lesions and ductal carcinoma in situ (DCIS). Concerning mass lesions, three were identified as DCIS and five as invasive ductal carcinoma (IDC). In conclusion, microcalcifications assessed in DM exhibit promising predictive characteristics concerning breast lesion subtypes, leading to a reduction in diagnostic times and further examination costs, thereby enhancing the clinical management of patients. Full article

Background/Objective: Sex-related differences among patients with aneurysmal subarachnoid hemorrhage (aSAH) and their potential clinical implications have been insufficiently investigated. To address this knowledge gap, we conduct a comprehensive systematic review and meta-analysis. Methods: Sex-specific differences in patients with aSAH, including mortality, delayed cerebral ischemia (DCI), and functional outcomes were assessed. The functional outcome was dichotomized into favorable or unfavorable based on the modified Rankin Scale (mRS), Glasgow Outcome Scale (GOS), and Glasgow Outcome Scale Extended (GOSE). Results: Overall, 2823 studies were identified in EMBASE, MEDLINE, PubMed, and by manual search on 14 February 2024. After an initial assessment, 74 studies were included in the meta-analysis. In the analysis of mortality, including 18,534 aSAH patients, no statistically significant differences could be detected (risk ratio (RR) 0.99; 95% CI, 0.90–1.09; p = 0.91). In contrast, the risk analysis for DCI, including 23,864 aSAH patients, showed an 11% relative risk reduction in DCI in males versus females (RR, 0.89; 95% CI, 0.81–0.97; p = 0.01). The functional outcome analysis (favorable vs. unfavorable), including 7739 aSAH patients, showed a tendency towards better functional outcomes in men than women; however, this did not reach statistical significance (RR, 1.02; 95% CI, 0.98–1.07; p = 0.34). Conclusions: In conclusion, the available data suggest that sex/gender may play a significant role in the risk of DCI in patients with aSAH, emphasizing the need for sex-specific management strategies. Full article

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2’s protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values < 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p < 0.0001), and a high proliferation index (p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact. Full article

Artificial intelligence (AI) has been implemented in multiple fields of medicine to assist in the diagnosis and treatment of patients. AI implementation in radiology, more specifically for breast imaging, has advanced considerably. Breast cancer is one of the most important causes of cancer mortality among women, and there has been increased attention towards creating more efficacious methods for breast cancer detection utilizing AI to improve radiologist accuracy and efficiency to meet the increasing demand of our patients. AI can be applied to imaging studies to improve image quality, increase interpretation accuracy, and improve time efficiency and cost efficiency. AI applied to mammography, ultrasound, and MRI allows for improved cancer detection and diagnosis while decreasing intra- and interobserver variability. The synergistic effect between a radiologist and AI has the potential to improve patient care in underserved populations with the intention of providing quality and equitable care for all. Additionally, AI has allowed for improved risk stratification. Further, AI application can have treatment implications as well by identifying upstage risk of ductal carcinoma in situ (DCIS) to invasive carcinoma and by better predicting individualized patient response to neoadjuvant chemotherapy. AI has potential for advancement in pre-operative 3-dimensional models of the breast as well as improved viability of reconstructive grafts. Full article