Nanostructure Lipid Carrier of Curcumin Co-Delivered with Linalool and Geraniol Monoterpenes as Acetylcholinesterase Inhibitor of Culex pipiens.

(1) Background: A molecular hybridization docking approach was employed to develop and detect a new category of naturally activated compounds against Culex pipiens as acetylcholinesterase inhibitors via designing a one-pot multicomponent nano-delivery system. (2) Methods: A nanostructure lipid carrier (NLC), as a second generation of solid lipid nanoparticles, was used as a carrier to deliver the active components of curcumin (Cur), geraniol (G), and linalool (L) in one nanoformulation after studying their applicability in replacing the co-crystallized ligand imidacloprid. (3) Results: The prepared nanostructure showed spherical-shaped, polydisperse particles ranging in size from 50 nm to 300 nm, as found using a transmission electron microscope. Additionally, dynamic light scattering confirmed an average size of 169 nm and a highly stable dispersed solution, as indicated by the zeta potential (-38 mV). The prepared NLC-Cur-LG displayed competitive, high-malignancy insecticidal activity against fourth instar C. pipiens with an elevated rate of death of 0.649 µg/mL. The treatment, due to the prepared nanostructure, affects oxidative stress enzymes, e.g., hydrogen peroxide (4 ppm), superoxide dismutase (SOD) (0.03 OD/mg), and protein carbonyl (0.08 OD/mg), and there are observable upward and downward fluctuations when using different concentrations of NLC-Cur-LG, suggesting significant problems in its foreseeable insecticidal activity. The acetylcholinesterase activity was assessed by an enzyme inhibition assay, and strengthened inhibition occurred due to the encapsulated NLCs (IC50 = 1.95 µg/mL). An investigation of the gene expression by Western blotting, due to treatment with NLC-Cur-LG, revealed a severe reduction of nearly a quarter of what was seen in the untreated group. As a preliminary safety step, the nanoformulation's toxicity against normal cell lines was tested, and a reassuring result was obtained of IC50 = 158.1 µg/mL for the normal lung fibroblast cell line. (4) Conclusions: the synthesized nanoformulation, NLC-Cur-LG, is a useful insecticide in field conditions.

Functional and oncological outcome of patients with benign hindfoot tumors treated by curettage.

BACKGROUND: Only 3 % of osseous tumors occur in the foot. The metatarsals are the -most common site whereas the calcaneus and talus are less common sites. Because these tumors are rare, the aim of our study is to assess the functional and the oncological outcome of patients with benign hindfoot tumors managed by curettage. METHODS: The clinical and radiological data of 41 patients diagnosed with benign hindfoot tumors were retrospectively reviewed. The study included 31 males and 10 females. The average age was 23.68 (range, 5-49) years. The average follow-up period was 92.7 (range, 12-244) months. RESULTS: At the last follow-up visit, the average Musculoskeletal Tumor Society scoring system (MSTS) score was 28.12 (range, 21-30). MSTS scores were higher in patients with latent tumors (P = .028) and patients managed by simple curettage (P = .018). The recurrence rate in calcaneal tumors was higher than those in the talus. The overall complication rate was 12.2 % (5 of 41 patients). Infection and subtalar arthritis were the most common complications. CONCLUSION: Curettage of benign bone tumors of talus or calcaneus proved to be an effective method in the management of these patients. Their functional outcome is also excellent. All the complications are manageable without long term morbidity. LEVEL OF EVIDENCE: Level IV Therapeutic study.

Immunohistochemical Expression of Claudin-1 and Claudin-4 in Urothelial Carcinoma of the Urinary Bladder.

BACKGROUND: In Egypt, bladder cancer occupies the second rankamong reported cancers in men. Claudins are tight junctions that have a critical role in tumor pathogenesis, invasion, progression, and metastasis and currentlyare a focus of interest for targeting therapies. OBJECTIVES: We aimed to evaluatethe immunohistochemical expression of Claudin-1 and Claudin-4 in urinary bladder urothelial carcinoma and investigate the relationshipbetweenthe expressed Claudins with differentclinicopathological parameters. METHODS: Claudin-1 and Claudin-4 immunohistochemical expression was studied in 62 cases of urinary bladder urothelial carcinomas. The cases were classified into two categories; low and high Claudin-1 and Claudin-4 expression. RESULTS: High Claudin-1 expression was detected in67.7% of the studied urothelial carcinomas while 32.3% showed low expression. Claudin-1 expression was reduced significantly with high tumor grade, non-papillary tumors, muscle invasion, schistosomal infestation, and perineural invasion (p-value < 0.05). Claudin-4 high expression was detected in 82.3% of our cases while low expression was detected in 17.7%. Claudin-4 reduced expression was significantly associated with non-papillary tumors, muscle invasion, advanced T stages, and associated lympho-vascular emboli (P-value < 0.05). CONCLUSION: According to the results ofthe present study, the reduced expressions of Claudin-1 and Claudin-4 provide clues concerning the progression of urothelial carcinoma. Consequently, it is thought that Claudin-1 and Claudin-4 could help to differentiatelow-grade from high-grade and muscle-invasive from non-muscle-invasive urothelial carcinomas. In addition, it can be introduced as a possible therapeutic target.

Utility of 2-Chloro-N-arylacetamide and 1,1'-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines].

A series of novel thieno[2,3-b]pyridines linked to N-aryl carboxamides or (carbonylphenoxy)-N-(aryl)acetamides, as well as bis(thieno[2,3-b]pyridines) linked to piperazine core via methanone or carbonylphenoxyethanone units, were synthesized by treating the appropriate chloroacetyl- or bis-bromoacetyl derivatives with 2-mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. The spectral data were used to determine the compositions of novel compounds.

Transcatheter aortic valve replacement in patients with severe aortic valve stenosis and concomitant mitral valve regurgitation - 5 years follow-up.

Objectives: To investigate the change in severity of mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR) and its effect on 5-year mortality. Background: There is inconsistency in literature on pre-existing MR influencing long-term survival in patients who undergo TAVR. Methods: Patients who underwent TAVR at the University Hospital Schleswig-Holstein (USKH) Campus Kiel between March 2009 and February 2018 have been enrolled. Echocardiography determined the degree of MR before and within 7 days after TAVR. Patients were divided into two groups according to their MR at baseline: MR-grade ≤ 2 (non-relevant MR, nr-MR) and baseline MR-grade > 2 (relevant MR, r-MR). Primary endpoint was a composite of MR baseline influence on mortality and MR reduction and its' impact on mortality. Results: A total of 820 patients (642 nr-MR and 178 in r-MR) were included in this study. Of these, 167 patients showed an improvement in MR-grade. Thereof 106 (63.5 %) referred to r-MR with a significant decrease in mean MR-grade (p < 0.01). Systolic pulmonary artery pressure (sPAP) (p < 0.01) and NT-proBNP (p = 0.03) decreased in patients who had an improvement. There was no significant difference in 5-year mortality for MR at baseline (p = 0.35) or reduction in mortality for r-MR patients with an MR improvement compared to patients with worsening or equal MR status (p = 0.80). Conclusion: In patients undergoing TAVR, 63.5 % of patients with MR-grade ≥ 2 at baseline showed an improvement of grade of MR after TAVR with reduction of their sPAP and NT-proBNP values but there was no significant difference in mortality.

Synthesis of Novel Diphenyl Ether-Based Bis-Heterocycles as Novel Hybrid Molecules via Michael and Other Cyclocondensation Reactions.

Molecular hybridization is a technique used in drug creation that involves combining the pharmacophoric moieties of multiple bioactive compounds to create a new hybrid molecule with better affinity and effectiveness. In this regard, we created unique hybrid molecules out of diphenyl ether-linked fused pyrans and other heterocycles. The Michael reaction of 4,4'-oxydibenzaldehyde with malononitrile and various active methylene derivatives, as well as enaminone derivatives, produced the matching bis-fused pyrans and fused pyridines, both connected to a diphenyl ether moiety. Furthermore, the acid-catalyzed reaction of 4,4'-oxydibenzaldehyde with dimedone or ß-naphthol produced the corresponding new bis(hexahydro-1H-xanthene-1,8-dione) and bis(14H-dibenzo[a,j]xanthene). The processes by which the target products are formed were also examined.

Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: Synthesis, docking, and antimicrobial activity.

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity.

A contemporary training concept in critical care cardiology.

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee's individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Synthesis and Anti-Breast Cancer Potency of Mono- and Bis-(pyrazolyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine) Derivatives as EGFR/CDK-2 Target Inhibitors.

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino-s-triazole-3-thiols 3a-c and bis(4-amino-5-mercapto-s-triazol-3-yl)alkanes 5a-d, respectively. The bis(6-pyrazolyl-s-triazolo[3,4-b][1,3,4]thiadiazine) derivatives 8a,b and 10 were also constructed by reaction of the triazolo[3,4-b][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a,b and 9, respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b, 4c, and 6a showed potent cytotoxicity against MCF-7 (IC50 = 3.16, 2.74, and 0.39 µM, respectively) and were safe against the MCF-10A cells. Compounds 4b, 4c, and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 µM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control).

Synthesis of novel mono- and bis-pyrazolylthiazole derivatives as anti-liver cancer agents through EGFR/HER2 target inhibition.

3-Bromoacetyl-4-(2-naphthoyl)-1-phenyl-1H-pyrazole (6) was synthesized from 2-acetylnaphthalene and was used as a new key building block for constructing the title targets. Thus, the reaction of 6 with the thiosemicarbazones 7a-d and 9-11 afforded the corresponding simple naphthoyl-(3-pyrazolyl)thiazole hybrids 8a-d and 12 ~ 14. The symmetric bis-(2-naphthoyl-pyrazol-3-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)alkanes 18a-c and 21a-c were similarly synthesized from reaction of 6 with the appropriate bis-thiosemicarbazones 17a-c and 19a-c, respectively. The synthesized two series of simple and symmetrical bis-molecular hybrid merging naphthalene, thiazole, and pyrazole were evaluated for their cytotoxicity. Compounds 18b,c and 21a showed the most potent cytotoxicity (IC50 = 0.97-3.57 µM) compared to Lapatinib (IC50 = 7.45 µM). Additionally, they were safe (non-cytotoxic) against the THLE2 cells with higher IC50 values. Compounds 18c exhibited promising EGFR and HER-2 inhibitory activities with IC50 = 4.98 and 9.85 nM, respectively, compared to Lapatinib (IC50 = 6.1 and 17.2 nM). Apoptosis investigation revealed that 18c significantly activated apoptotic cell death in HepG2 cells, increasing the death rate by 63.6-fold and arresting cell proliferation at the S-phase. Compound 18c upregulated P53 by 8.6-fold, Bax by 8.9-fold, caspase-3,8,9 by 9, 2.3, and 7.6-fold, while it inhibited the Bcl-2 expression by 0.34-fold. Thereby, compound 18c exhibited promising cytotoxicity against EGFR/HER2 inhibition against liver cancer.

Novel Scaffolds Based on Bis-thiazole Connected to Quinoxaline or Thienothiophene through 2-Phenoxy-N-arylacetamide Groups as New Hybrid Molecules: Synthesis, Antibacterial Activity, and Molecular Docking Investigations.

The resistance of microorganisms to antimicrobials has endangered the health of many people across the world. Overcoming the resistance problem will require the invention of molecules with a new mechanism of action so that no cross-resistance with existing therapies occurs. Because of their powerful antibacterial activity against a wide spectrum of Gram-positive and Gram-negative bacterial strains, heterocyclic compounds are appealing candidates for medicinal chemists. In this regard, as unique hybrid compounds, we synthesized a novel family of bis-thiazoles linked to quinoxaline or thienothiophene via the 2-phenoxy-N-arylacetamide moiety. The target compounds were synthesized by reacting the relevant bis(α-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux with a few drops of TEA. Under comparable reaction conditions, the isomeric bis(thiazoles) were synthesized by reacting the appropriate bis(thiosemicarbazone) with the respective α-haloketones. The structures of the novel compounds were confirmed using elements and spectral data. All of the synthesized compounds were tested for antibacterial activity in vitro. With an inhibitory zone width of 12 mm, compound 12a had the same activity as the reference medication tobramycin against Staphylococcus aureus. Compound 12b showed 20 mg/mL as a minimum inhibitory concentration (MIC) against Bacillus subtilis. Some of the synthesized compounds were tested via molecular docking against two bacterial proteins (dihydrofolate reductase and tyrosyl-tRNA synthetase).

Before and Amid COVID-19 Pandemic, Self-Perception of Digital Skills in Saudi Arabia Higher Education: A Longitudinal Study.

Compatible with global sustainable development report, 2016 edition, and vision 2030, Saudi Arabia recognized the importance of technology in achieving the Sustainable Development Goals (SDGs). This paper aims to measure the self-perception of digital skills among students in Saudi Arabia's higher education system to understand how they were influenced before and amid the COVID-19 pandemic. In 2019 before the COVID-19 pandemic, we started a project to study the self-perception of digital skills among Saudi Arabia university students (group A). A total of 469 students participated in this research. The validity and reliability of the employed scale were tested with first-order confirmatory factor analysis (CFA). The differences between the two groups (before and amid the pandemic) were tested through the Mann-Whitney U test. The results for group A (N = 232 students) showed a higher self-perception of their digital skills. In March 2020, amid the pandemic, Saudi Arabia closed and shifted to technology-based teaching like many other countries worldwide. After students' return to universities in 2021, an evaluation of how the students perceived their own digital skills was again conducted (group B). The results for group B (N = 237 students) demonstrated a lower level of confidence in their own digital abilities. Comparing two groups (A and B), after the educational course was administered, group A (prior to COVID-19) had greater self-perceptions of digital skills than group B (amid COVID-19). Students' perceptions of their own digital skills have been negatively impacted as a result of the pandemic situation caused by COVID-19. The collected evidence suggests that there is a difference, and that this difference is statistically significant. As a result of the substantial relationship between self-perception of digital skills and how students deal with reality based on their own self-perception, Saudi Arabia higher education ministry shifted teaching methods to be based on technology. Other significant findings and their implications for practice and theory were reported in this study. Finally, limitations and prospects for future research were also elaborated.

ADIDAS: An Examined Approach for Enhancing Cognitive Load and Attitudes towards Synchronous Digital Learning Amid and Post COVID-19 Pandemic.

SARS-CoV-2 (COVID-19) has disrupted university education and turned it into distance learning for at least one semester in many countries, including the Kingdom of Saudi Arabia (KSA). However, there was an issue with university students' cognitive load at this critical time, because education totally stopped for about a month and then resumed remotely. This research draws on the cognitive load theory, particularly the extraneous load, to develop an instructional design model called ADIDAS. The model includes six stages, namely: analyse (A), design (D), improve (I), do (D), Assess (A), and Share (S). Thirty-four experts in instructional technology models have reviewed the ADIDAS model in Arab university contexts, producing a consensus about its suitability for use in distance learning amid the COVID-19 pandemic. Following the consensus of the experts, the model was applied to a sample of 527 students at King Faisal University, KSA. The results confirmed significant statistical differences with a very large effect size in relation to the attitude towards synchronous digital learning (SDL) and cognitive load pre and post ADIDAS. Students had a positive attitude towards SDL and a low cognitive load during the educational process pre adoption of the ADIDAS model, compared to post ADIDAS. The current research results have numerous implications for post the COVID-19 pandemic, especially in Arab countries and similar contexts.

The Impact of Tumor Infiltrating Lymphocytes Densities and Ki67 Index on Residual Breast Cancer Burden following Neoadjuvant Chemotherapy.

To avoid unnecessary neoadjuvant chemotherapy in case anticipating a poor therapy response, it is essential to find the pathological parameters that would predict pathological complete response or at least a decrease in tumor burden following neoadjuvant chemotherapy. The purpose of this study is to investigate the hypothesis that tumor infiltrating lymphocytes can predict the efficacy of neoadjuvant chemotherapy and to find the Ki67 cutoff value that best predicts the benefit of chemotherapy. 153 cases of breast cancer were chosen, based on their molecular subtype: triple negative subtype (77) and luminal, HER2-ve subtype (76). Histopathological assessment of pretherapy core biopsies was conducted to assess variable pathological parameters including TILs rates with the aid of immunohistochemical staining for CD20 and CD3. Moreover, core biopsies were stained for Ki67, and the findings were compared to the residual cancer burden following neoadjuvant chemotherapy. On analyzing and contrasting the two groups, a significant association between molecular subtype and pathological complete response was confirmed, while tumor-infiltrating lymphocytes in either group had no effect on therapy response. We used receiver operating characteristic curve analysis to determine that a cutoff of 36% for Ki67 is the most accurate value to predict complete therapy response.

Evaluating the use of synthetic T1-w images in new T2 lesion detection in multiple sclerosis.

The assessment of disease activity using serial brain MRI scans is one of the most valuable strategies for monitoring treatment response in patients with multiple sclerosis (MS) receiving disease-modifying treatments. Recently, several deep learning approaches have been proposed to improve this analysis, obtaining a good trade-off between sensitivity and specificity, especially when using T1-w and T2-FLAIR images as inputs. However, the need to acquire two different types of images is time-consuming, costly and not always available in clinical practice. In this paper, we investigate an approach to generate synthetic T1-w images from T2-FLAIR images and subsequently analyse the impact of using original and synthetic T1-w images on the performance of a state-of-the-art approach for longitudinal MS lesion detection. We evaluate our approach on a dataset containing 136 images from MS patients, and 73 images with lesion activity (the appearance of new T2 lesions in follow-up scans). To evaluate the synthesis of the images, we analyse the structural similarity index metric and the median absolute error and obtain consistent results. To study the impact of synthetic T1-w images, we evaluate the performance of the new lesion detection approach when using (1) both T2-FLAIR and T1-w original images, (2) only T2-FLAIR images, and (3) both T2-FLAIR and synthetic T1-w images. Sensitivities of 0.75, 0.63, and 0.81, respectively, were obtained at the same false-positive rate (0.14) for all experiments. In addition, we also present the results obtained when using the data from the international MSSEG-2 challenge, showing also an improvement when including synthetic T1-w images. In conclusion, we show that the use of synthetic images can support the lack of data or even be used instead of the original image to homogenize the contrast of the different acquisitions in new T2 lesions detection algorithms.

Improving the detection of new lesions in multiple sclerosis with a cascaded 3D fully convolutional neural network approach.

Longitudinal magnetic resonance imaging (MRI) has an important role in multiple sclerosis (MS) diagnosis and follow-up. Specifically, the presence of new lesions on brain MRI scans is considered a robust predictive biomarker for the disease progression. New lesions are a high-impact prognostic factor to predict evolution to MS or risk of disability accumulation over time. However, the detection of this disease activity is performed visually by comparing the follow-up and baseline scans. Due to the presence of small lesions, misregistration, and high inter-/intra-observer variability, this detection of new lesions is prone to errors. In this direction, one of the last Medical Image Computing and Computer Assisted Intervention (MICCAI) challenges was dealing with this automatic new lesion quantification. The MSSEG-2: MS new lesions segmentation challenge offers an evaluation framework for this new lesion segmentation task with a large database (100 patients, each with two-time points) compiled from the OFSEP (Observatoire français de la sclérose en plaques) cohort, the French MS registry, including 3D T2-w fluid-attenuated inversion recovery (T2-FLAIR) images from different centers and scanners. Apart from a change in centers, MRI scanners, and acquisition protocols, there are more challenges that hinder the automated detection process of new lesions such as the need for large annotated datasets, which may be not easily available, or the fact that new lesions are small areas producing a class imbalance problem that could bias trained models toward the non-lesion class. In this article, we present a novel automated method for new lesion detection of MS patient images. Our approach is based on a cascade of two 3D patch-wise fully convolutional neural networks (FCNNs). The first FCNN is trained to be more sensitive revealing possible candidate new lesion voxels, while the second FCNN is trained to reduce the number of misclassified voxels coming from the first network. 3D T2-FLAIR images from the two-time points were pre-processed and linearly co-registered. Afterward, a fully CNN, where its inputs were only the baseline and follow-up images, was trained to detect new MS lesions. Our approach obtained a mean segmentation dice similarity coefficient of 0.42 with a detection F1-score of 0.5. Compared to the challenge participants, we obtained one of the highest precision scores (PPVL = 0.52), the best PPVL rate (0.53), and a lesion detection sensitivity (SensL of 0.53).

Cardiac Myxomas Resembling Malignant Neoplasia: Incidentally Diagnosed vs. Cerebral Embolized Myxomas.

Background: Cardiac myxomas (CM) are the most common primary cardiac tumors in adults. They are usually benign; however, malignant changes are known to occur but are extremely rare. Embolization is a common complication of cardiac myxomas and can cause neurological deficits before their surgical removal. The current study analyzed the outcomes after operative myxoma excision in patients, with and without cerebral embolic events prior to excision. Methods: All 66 consecutive patients who underwent a surgical excision of CM between 2005 and 2019 at our department were analyzed retrospectively. Patients with (n = 14) and without (n = 52) preoperative strokes caused by cerebral tumor embolization were compared. Results: The mean age was 58.4 ± 12.7 years in the stroke group (SG) and 62.8 ± 11.7 years in the non-stroke group (N-SG) (p = 0.226). Gender (35.7% vs. 61.5% female; p = 0.084) did not differ significantly, and comorbidities were comparable in both groups. The left hemisphere in the territory of the middle cerebral artery was affected by preoperative cerebral infarction most commonly (28.6%). The time from diagnosis to cardiac surgery procedure was 7 (3−24) days in the SG and 23 (5−55) days in the N-SG (p = 0.120). Cardiac myxomas were localized in the left atrium in both groups more frequently (SG: 92.9% vs. N-SG: 78.8%; p = 0.436). In the SG, 57.1% of CM had a non-solid surface, were localized in the left heart, and had a pedunculated attachment away from the fossa ovalis. In the N-SG, 92.3% of CM did not meet all these criteria (p < 0.001). The maximal diameters of CM were comparable (SG: 3.4 ± 1.5 cm vs. N-SG: 3.8 ± 2.1 cm; p = 0.538). The operation times (192.5 (139.3−244.5) min vs. 215.5 (184.5−273.3) min; p = 0.046) and the cross-clamp times (54.5 (33.3−86.5) min vs. 78.5 (55−106.8) min; p = 0.035) were significantly shorter in the SG. Only in the N-SG were reconstructions of the endocardium with bovine pericardium required after resection (51.9% vs 0%; p < 0.001). In the N-SG, CM were explored via the right atrium more often (57.7% vs. 14.3%; p = 0.007). Patients in the N-SG required significantly shorter ICU care after surgery (p = 0.020). Other postoperative courses did not differ significantly. After tumor removal, 1.9% of the N-SG suffered their first stroke and 14.3% of the SG had a cerebral re-infarction (p = 0.111). The 30-day mortality rates were 1.9% in the N-SG and 7.1% in the SG (p = 0.382). In one case in the N-SG, a tumor recurrence was diagnosed. The Kaplan−Meiercurves showed a significantly better long-term prognosis for patients in the N-SG (p = 0.043). Conclusions: After the surgical removal of CM, the outcome is compromised if preoperative cerebral embolization occurs. Surgical treatment is therefore indicated as soon as possible, especially when CM have a non-solid surface, are localized in the left heart, and have a pedunculated attachment away from the fossa ovalis.

Transductive Transfer Learning for Domain Adaptation in Brain Magnetic Resonance Image Segmentation.

Segmentation of brain images from Magnetic Resonance Images (MRI) is an indispensable step in clinical practice. Morphological changes of sub-cortical brain structures and quantification of brain lesions are considered biomarkers of neurological and neurodegenerative disorders and used for diagnosis, treatment planning, and monitoring disease progression. In recent years, deep learning methods showed an outstanding performance in medical image segmentation. However, these methods suffer from generalisability problem due to inter-centre and inter-scanner variabilities of the MRI images. The main objective of the study is to develop an automated deep learning segmentation approach that is accurate and robust to the variabilities in scanner and acquisition protocols. In this paper, we propose a transductive transfer learning approach for domain adaptation to reduce the domain-shift effect in brain MRI segmentation. The transductive scenario assumes that there are sets of images from two different domains: (1) source-images with manually annotated labels; and (2) target-images without expert annotations. Then, the network is jointly optimised integrating both source and target images into the transductive training process to segment the regions of interest and to minimise the domain-shift effect. We proposed to use a histogram loss in the feature level to carry out the latter optimisation problem. In order to demonstrate the benefit of the proposed approach, the method has been tested in two different brain MRI image segmentation problems using multi-centre and multi-scanner databases for: (1) sub-cortical brain structure segmentation; and (2) white matter hyperintensities segmentation. The experiments showed that the segmentation performance of a pre-trained model could be significantly improved by up to 10%. For the first segmentation problem it was possible to achieve a maximum improvement from 0.680 to 0.799 in average Dice Similarity Coefficient (DSC) metric and for the second problem the average DSC improved from 0.504 to 0.602. Moreover, the improvements after domain adaptation were on par or showed better performance compared to the commonly used traditional unsupervised segmentation methods (FIRST and LST), also achieving faster execution time. Taking this into account, this work presents one more step toward the practical implementation of deep learning algorithms into the clinical routine.

Calculated Plasma Volume Status Is Associated with Adverse Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Calculated plasma volume status (PVS) reflects volume overload based on the deviation of the estimated plasma volume (ePV) from the ideal plasma volume (iPV). Calculated PVS is associated with prognosis in the context of heart failure. This single-center study investigated the prognostic impact of PVS in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: A total of 859 TAVI patients had been prospectively enrolled in an observational study and were included in the analysis. An optimal cutoff for PVS of -5.4% was determined by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization within 1 year after TAVI. RESULTS: A total of 324 patients had a PVS < -5.4% (no congestion), while 535 patients showed a PVS ≥ -5.4% (congestion). The primary endpoint occurred more frequently in patients with a PVS ≥ -5.4% compared to patients with PVS < -5.4% (22.6% vs. 13.0%, p < 0.001). After multivariable adjustment, PVS was confirmed as a significant predictor of the primary endpoint (HR 1.53, 95% CI 1.05-2.22, p = 0.026). CONCLUSIONS: Elevated PVS, as a marker of subclinical congestion, is significantly associated with all-cause mortality and heart failure hospitalization within 1 year after TAVI.