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To enhance M-mode echocardiography's utility for measuring cardiac structures, we developed and evaluated an artificial intelligence (AI)-based automated analysis system for M-mode images through the aorta and left atrium [M-mode (Ao-LA)], and through the left ventricle [M-mode (LV)]. Our system, integrating two deep neural networks (DNN) for view classification and image segmentation, alongside an auto-measurement algorithm, was developed using 5,958 M-mode images [3,258 M-mode (LA-Ao), and 2,700 M-mode (LV)] drawn from a nationwide echocardiographic dataset collated from five tertiary hospitals. The performance of view classification and segmentation DNNs were evaluated on 594 M-mode images, while automatic measurement accuracy was tested on separate internal test set with 100 M-mode images as well as external test set with 280 images (140 sinus rhythm and 140 atrial fibrillation). Performance evaluation showed the view classification DNN's overall accuracy of 99.8% and segmentation DNN's Dice similarity coefficient of 94.3%. Within the internal test set, all automated measurements, including LA, Ao, and LV wall and cavity, resonated strongly with expert evaluations, exhibiting Pearson's correlation coefficients (PCCs) of 0.81–0.99. This performance persisted in the external test set for both sinus rhythm (PCC, 0.84–0.98) and atrial fibrillation (PCC, 0.70–0.97). Notably, automatic measurements, consistently offering multi-cardiac cycle readings, showcased a stronger correlation with the averaged multi-cycle manual measurements than with those of a single representative cycle. Our AI-based system for automatic M-mode echocardiographic analysis demonstrated excellent accuracy, reproducibility, and speed. This automated approach has the potential to improve efficiency and reduce variability in clinical practice. Artificial intelligence (AI)-based pipeline for automated M-mode echocardiography analysis. The M-mode echocardiography analysis algorithm consists of a pipeline of two interconnected deep neural networks and an automated measurement algorithm. The first network classifies two different M-mode echocardiographic views, and the second segments M-mode echocardiographic images. The corresponding auto-measurements were then performed. [ABSTRACT FROM AUTHOR]

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations. [ABSTRACT FROM AUTHOR]

Laser-assisted recovery of on-chip phage viral DNA was demonstrated. Optomechanical energy conversion was utilized to shear off a part of a microchip and thereby form a micropellet. The micropellets carrying phage samples were directed to conventional laboratory circumstances for downstream analysis, addressing a 'chip-to-world' interface issue in lab-on-a-chip technology. Phage viral DNA content carried by the micropellets was validated through quantification and sequence verification. The developed microchip configuration and its localized sample retrieval would function as a high-throughput sample handling method compatible with microchip-based phage fluorescence immunoassay. [ABSTRACT FROM AUTHOR]

Objective: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. Methods: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. Results: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (− 6.7 ± 2.4 vs. − 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, − 15.5 ± 4.0 to − 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). Conclusions: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. Clinical relevance statement: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. Key Points: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve. [ABSTRACT FROM AUTHOR]

Until recently, conventional biochemical staining had the undisputed status as well-established benchmark for most biomedical problems related to clinical diagnostics, fundamental research and biotechnology. Despite this role as gold-standard, staining protocols face several challenges, such as a need for extensive, manual processing of samples, substantial time delays, altered tissue homeostasis, limited choice of contrast agents, 2D imaging instead of 3D tomography and many more. Label-free optical technologies, on the other hand, do not rely on exogenous and artificial markers, by exploiting intrinsic optical contrast mechanisms, where the specificity is typically less obvious to the human observer. Over the past few years, digital staining has emerged as a promising concept to use modern deep learning for the translation from optical contrast to established biochemical contrast of actual stainings. In this review article, we provide an in-depth analysis of the current state-of-the-art in this field, suggest methods of good practice, identify pitfalls and challenges and postulate promising advances towards potential future implementations and applications. [ABSTRACT FROM AUTHOR]

We aimed to investigate the detection rate of brain MR and MR angiography for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients with/without neurological symptoms. This retrospective study included consecutive patients with definite or possible left-sided infective endocarditis according to the modified Duke criteria who underwent brain MRI and MR angiography between March 2015 and October 2020. The detection rate for neuroimaging abnormality on MRI was defined as the number of patients with positive brain MRI findings divided by the number of patients with left-sided infective endocarditis. Positive imaging findings included acute ischemic lesions, cerebral microbleeds, hemorrhagic lesions, and infectious aneurysms. In addition, aneurysm rupture rate and median period to aneurysm rupture were evaluated on follow-up studies. A total 115 patients (mean age: 55 years ± 19; 65 men) were included. The detection rate for neuroimaging abnormality was 77% (89/115). The detection rate in patients without neurological symptoms was 70% (56/80). Acute ischemic lesions, cerebral microbleeds, and hemorrhagic lesions including superficial siderosis and intracranial hemorrhage were detected on MRI in 56% (64/115), 57% (66/115), and 20% (23/115) of patients, respectively. In particular, infectious aneurysms were detected on MR angiography in 3% of patients (4/115), but MR angiography in 5 patients (4.3%) was insignificant for infectious aneurysm, which were detected using CT angiography (n = 3) and digital subtraction angiography (n = 2) during follow-up. Among the 9 infectious aneurysm patients, aneurysm rupture occurred in 4 (44%), with a median period of aneurysm rupture of 5 days. The detection rate of brain MRI for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients was high (77%), even without neurological symptoms (70%). [ABSTRACT FROM AUTHOR]

Objective: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included.Results: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement.Conclusions: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery.Key Points: • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients. [ABSTRACT FROM AUTHOR]

A museum exhibit that enables direct full-body interactions with living microbes immerses human visitors into the microscopic world and could inform the design of future educational life-science technologies. [ABSTRACT FROM AUTHOR]

Introduction: The role of unicompartmental knee arthroplasty (UKA) in spontaneous osteonecrosis of the knee (SONK) remains controversial, even though SONK involves only one compartment of the knee joint. We aimed to compare the survival rate and clinical outcomes of UKA in SONK and medial compartment osteoarthritis (MOA) via a meta-analysis of previous studies.Materials and Methods: MEDLINE, Embase, and Cochrane Library were searched up to January 2018 with keywords related to SONK and knee arthroplasty. Studies were selected with predetermined inclusion criteria: (1) medial UKA as the primary procedure, (2) reporting implant survival or clinical outcomes of osteonecrosis and osteoarthritis, and (3) follow-up period > 1 year. Quality assessment was performed using the risk of bias assessment tool for non-randomized studies. A random-effects model was used to estimate the pooled relative risk (RR) and standardized mean difference.Results: The incidence of UKA revision for any reason was significantly higher in SONK than in MOA group (pooled RR = 1.83, p = 0.009). However, the risk of revision due to aseptic loosening was not significantly different between the groups. Moreover, when stratified by the study quality, high-quality studies showed similar risk of overall revision in SONK and MOA (p = 0.71). Subgroup analysis revealed no significant difference in failure between SONK and MOA after cemented mobile and fixed bearing UKA. Results of uncemented UKA were reported only in one study, which showed higher failure of SONK compared to MOA. Clinical outcomes after UKA were similar between SONK and MOA (p = 0.66).Conclusions: Cemented UKA has similar survival and clinical outcomes in SONK and MOA. Prospective studies designed specifically to compare the UKA outcomes in SONK and MOA are necessary. [ABSTRACT FROM AUTHOR]

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient's 12-lead ECG. During a mean 15.6 years (range 3.3-30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22-2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15-2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03-1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01-1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score ( r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF. [ABSTRACT FROM AUTHOR]

Therapeutic irradiation can cause bone loss, whereas antioxidant supplementation is considered to attenuate irradiation-mediated damages. This study examined whether or not acteoside inhibits irradiation-mediated changes in viability and proliferation of MC3T3-E1 cells. X-ray radiation at >4 Gy not only decreased cell viability and DNA synthesis in the cells, but also increased intracellular levels of reactive oxygen species (ROS) and phosphorylated p66 protein. Irradiation at 8Gy also decreased intracellular levels of reduced glutathione (GSH) and induced G phase arrest of cell cycle progression with the attendant increase of p21 induction. Pretreatment with acteoside inhibited the irradiation-mediated decreases in viability and DNA synthesis by restoring the radiation-mediated changes in the levels of ROS, GSH, p21, and p-p66 to the untreated control levels. These inhibitory activities of acteoside were greater than that of a synthetic antioxidant compound or N-acetyl cysteine did. Collectively, acteoside treatment may prevent irradiation-induced oxidative damages to osteoblasts. [ABSTRACT FROM AUTHOR]

Ascorbic acid, a potential antioxidant, is known to inhibit melanogenesis. However, there are conflicting findings that ascorbic acid has very low stability and acts as a pro-oxidant, eventually increasing proliferation and melanin content in melanoma cells. In the present study, we explored the effects of ascorbic acid on the activity and expression of tyrosinase and melanin pigmentation in the presence and absence of α-melanocyte-stimulating hormone (α-MSH) using B16F10 melanoma cells. The mechanism by which ascorbic acid stimulated the expression of tyrosinase was also investigated. No inhibitory effect on melanin content was observed in ascorbic acid-treated cells, regardless of the presence of α-MSH. Ascorbic acid stimulated the activity and expression of tyrosinase and increased the expression of melanogenic regulatory factors, such as tyrosinase-related protein-1 (TRP-1), dihydroxyphenylalaminechrome tautomerase (TRP-2), and microphthalmia-associated transcription factor (MITF). Ascorbic acid also induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). The inhibition of p38 MAPK pathway by SB203580 led to the suppression of tyrosinase, TRP-1, and TRP-2 expression in cells treated with ascorbic acid. Combined treatment with N-acetyl- l-cysteine and/or desferrioxamine mesylate attenuated the stimulating effect of ascorbic acid on tyrosinase activation in the cells. Collectively, ascorbic acid stimulates tyrosinase activity and expression in B16F10 cells via activation of p38 MAPK signaling and subsequent up-regulation of MITF, tyrosinase, and TRP expression. [ABSTRACT FROM AUTHOR]

Flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine that has long been used in Korea as both a food additive and antitumor agent. It was previous reported that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), inhibited the proliferation and induced apoptosis in human osteosarcoma (HOS) cells. This study examined the mechanisms involved in the RCMF-mediated apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis in HOS cells by inducing p53 in the cells resulting in the decrease in Bcl-2 level, activation of Bax, and cytoplasmic release of cytochrome c, which led to the translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus. However, the RCMF-induced apoptosis was suppressed by transfecting the cells with antisense p53 oligonucleotides but not by treating them with a MAPK or caspase inhibitor. This suppression occurred through the regulation of Bcl-2 members as well as by preventing the nuclear translocation of the mitochondrial apoptogenic factors. Overall, it appears that p53-mediated mitochondrial stress and the nuclear translocation of AIF and EndoG are mainly required for the apoptosis induced by RCMF. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine whether temporal values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) after total knee arthroplasty (TKA) differ between patients with and without elevated preoperative CRP. We hypothesized that temporal pattern of CRP and ESR change would differ between the two groups., Materials and Methods: This retrospective study included 30 TKAs with a diagnosis of osteoarthritis with elevated preoperative CRP (>1 mg/dl) without clinical signs and symptoms of infection before surgery (elevated CRP group). Patients without elevated preoperative CRP were matched in a 1:10 fashion according to age, sex, number of comorbidities and whether TKA was unilateral or bilateral (nonelevated CRP group). The temporal values of CRP and ESR after TKA were compared between the two groups until 2 months after surgery., Results: The mean peak values of CRP and ESR after surgery were similar between the two groups in both unilateral and bilateral TKAs. In the unilateral TKA, mean values of CRP and ESR and the proportions of the knees with normal CRP and ESR at 2 months after surgery were similar in the two groups. However, in the bilateral TKA, mean values of CRP and ESR were higher and the proportions of the knees with normal CRP and ESR at 2 months after surgery were lower in the elevated CRP group compared to the nonelevated CRP group., Conclusions: When performing TKA in patients with elevated preoperative CRP, the fact that the levels of CRP and ESR may not be normalized until 2 months after surgery should be considered during followup., Competing Interests: There are no conflicts of interest.