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OBJECTIVES: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair - relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area. DESIGN: This was a retrospective observational study of patients who underwent mitral intervention between 2016 and 2020. SETTING: Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS: The population comprised of 50 degenerative mitral regurgitation (MR) patients undergoing MVr. INTERVENTIONS: Elective MVr and transesophageal echocardiography (TEE) MEASUREMENTS AND MAIN RESULTS: MitraClip or surgical MVr patients were matched (1:1) for gender and CAD. Mitral annular geometry indices were quantified on intra-procedural 3D TEE. Mild or less MR on follow-up TTE defined optimal response. MitraClip patients were older (80±8 vs. 66±6;p

Few studies have been conducted among Asian children and adolescents with type 1 diabetes mellitus (T1DM) using do-it-yourself artificial pancreas system (DIY-APS). We evaluated real-world data of pediatric T1DM patients using DIY-APS. Data were obtained for 10 patients using a DIY-APS with algorithms. We collected sensor glucose and insulin delivery data from each participant for a period of 4 weeks. Average glycosylated hemoglobin was 6.2%±0.3%. The mean percentage of time that glucose level remained in the target range of 70 to 180 mg/dL was 82.4%±7.8%. Other parameters including time above range, time below range and mean glucose were also within the recommended level, similar to previous commercial and DIY-APS studies. However, despite meeting the target range, unadjusted gaps were still observed between the median basal setting and temporary basal insulin, which should be handled by healthcare providers.

Hemorrhage after pancreaticobiliary surgery is an infrequent but fatal complication. It is primarily caused by rupture of the pseudoaneurysm, and treatment options include endovascular coil embolization or endovascular stent-graft placement. Herein, we report a case of migration of an arterial stent-graft that was placed in the common hepatic artery to treat pseudoaneurysm after pylorus-preserving pancreaticoduodenectomy. The stent-graft migrated to the jejunum and was eventually excreted from the body.

OBJECTIVES Among patients with ascending thoracic aortic aneurysms, prosthetic graft replacement yields major benefits but risk for recurrent aortic events persists for which mechanism is poorly understood. This pilot study employed cardiac magnetic resonance to test the impact of proximal prosthetic grafts on downstream aortic flow and vascular biomechanics. METHODS Cardiac magnetic resonance imaging was prospectively performed in patients with thoracic aortic aneurysms undergoing surgical (Dacron) prosthetic graft implantation. Imaging included time resolved (4-dimensional) phase velocity encoded cardiac magnetic resonance for flow quantification and cine-cardiac magnetic resonance for aortic wall distensibility/strain. RESULTS Twenty-nine patients with thoracic aortic aneurysms undergoing proximal aortic graft replacement were studied; cardiac magnetic resonance was performed pre- [12 (4, 21) days] and postoperatively [6.4 (6.2, 7.2) months]. Postoperatively, flow velocity and wall shear stress increased in the arch and descending aorta (P CONCLUSIONS Prosthetic graft replacement of the ascending aorta increases downstream aortic wall shear stress and strain. Postoperative increments in descending aortic wall shear stress correlate with reduced ascending aortic distensibility, suggesting that grafts provide a nidus for high energy flow and adverse distal aortic remodelling.

Background Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria. Objective The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV). Methods One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1–3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site. Results Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites. Conclusion ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. In primary endothelial cell cultures, we show that SARS-CoV-2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon-alpha (IFNα) or -beta(β)—two of the main anti-viral cytokines induced in severe SARS-CoV-2 infection—but not significantly by other cytokines (including interleukin 6 and interferon γ/λ). Our findings suggest that the stereotypical anti-viral interferon response may paradoxically facilitate the propagation of COVID-19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10456-021-09823-4.

Multispectral pedestrian detection has been actively studied as a promising multi-modality solution to handle illumination and weather changes. Most multi-modality approaches carry the assumption that all inputs are fully-overlapped. However, these kinds of data pairs are not common in practical applications due to the complexity of the existing sensor configuration. In this letter, we tackle multispectral pedestrian detection, where all input data are not paired. To this end, we propose a novel single-stage detection framework that leverages multi-label learning to learn input state-aware features by assigning a separate label according to the given state of the input image pair. We also present a novel augmentation strategy by applying geometric transformations to synthesize the unpaired multispectral images. In extensive experiments, we demonstrate the efficacy of the proposed method under various real-world conditions, such as fully-overlapped images and partially-overlapped images, in stereo-vision. Code and a demonstration video are available at https://github.com/sejong-rcv/MLPD-Multi-Label-Pedestrian-Detection .

Purpose: To analyze changes in the incidences of chronic and traumatic diseases before and after registration as visually disabled.Methods: The incidence and risk of chronic and traumatic diseases were compared between patients registered as visually disabled from 2005 to 2013 and a control group, selected through 1:1 propensity score matching for age, sex, premium quantile, and residential area distribution. Data from the National Health Insurance Service were used and the observation period was set from 2 years before to 5 years after the time of registration as visually disabled. The incidences (%) of chronic and traumatic diseases at the point of interest were determined as the mean values according to year of registration, and the risk was measured by conditional logistic regression analysis.Results: 131,434 visually disabled patients and the same number of non-visually impaired controls were included. The incidences of chronic disease and fall-related injury were higher in the visually disabled group before registration, but gradually decreased and became similar to the control group after registration. In addition, the risk of developing chronic diseases was higher in the visually disabled group until 2 years after registration, while the risk of fall-related injury remained consistently higher in the visually disabled group during the observation period. The incidence and risk of hip fracture in the visually disabled group increased gradually from approximately 1 year before registration and remained consistently higher than in the control group.Conclusions: People with visual disability have higher incidences of chronic diseases than do non-visually impaired people and are at greater risk of traumatic injuries, such as hip fractures or falls. There is a need to establish community infrastructure and expand welfare services for the prevention and early treatment of comorbidities, both for patients with registered visual disabilities and for patients who have not yet registered.

Objectives This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking–derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe functional tricuspid regurgitation. Background Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown. Methods Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models. Results Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (−16%) had significantly reduced event-free survival compared with those with RVFWLS Conclusions CMR feature-tracking–derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM.Methods: A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD.Results: Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters.Conclusion: The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinicalpractice.

Summary Background Tegoprazan is a novel, fast‐ and long‐acting potassium‐competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non‐erosive reflux disease (NERD), a type of gastroesophageal reflux disease. Aim To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD. Methods In this phase 3, double‐blind, placebo‐controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4‐week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated. Results Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn‐free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P, Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with non‐erosive reflux disease.

Background/Aims S-isomer (S) pantoprazole is more bioavailable and less dependent on cytochrome 2C19 than is racemic pantoprazole. We aim to evaluate the efficacy and safety of 10 mg S-pantoprazole for treatment of non-erosive reflux disease (NERD). Methods In this phase 3, double-blind, randomized placebo controlled, multicenter study, 174 NERD patients were randomized to one of both treatment groups: 10 mg S-pantoprazole, or placebo once daily for 4 weeks. Symptoms and safety were assessed. The efficacy endpoints were complete relief of symptoms, > 50% improvement of all reflux symptoms and recurrence. Results Eighty-eight patients were assigned to the S-pantoprazole group (25 males, mean 43.7 years old) and 86 to the placebo group (32 males, mean 43.0 years old), and 163 patients were subjected to full Analysis Set. A higher proportion of patients in the S-pantoprazole group had complete symptom relief (42.0 % [34/81] vs 17.1% [14/82], P 50% symptom responses (66.0% vs 50.0%, P = 0.010 for heartburn; 64.2% vs 28.0%, P = 0.010 for acid regurgitation; and 51.9% vs 30.5%, P = 0.03 for epigastric discomfort) compared to the placebo group. The factors associated with poor responsiveness to PPI were older age, female, greater body mass index, and severe baseline symptoms. Conclusions Low dose of S-pantoprazole (10 mg) for 4 weeks was more efficacious than placebo in providing reflux symptom relief in patients with NERD, especially acid regurgitation. More doses or longer periods of treatment with S-pantoprazole would be needed to completely eliminate symptoms. (J Neurogastroenterol Motil 2021;27:223-230)

The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Background/Aims: Ulcerative colitis (UC) is an inflammatory bowel disease for which new serological markers are required. The purpose of this study was to assess the role of the mucosa-associated epithelial chemokine CCL28 in UC. Methods: The study included 50 patients; of these, 25 were patients with UC, and 25 were healthy controls. The levels of serum CCL28 were analyzed using enzyme-linked immunosorbent assay. CCL28 expression was analyzed by immunohistochemistry (IHC) in 15 representative colon tissues biopsied based on disease activity (UC patients with severe activity, five samples; UC patients with mild activity, five samples; healthy controls, five samples). Results: The serum CCL28 levels were remarkably higher (p

Objective It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Methods Ten-week-old C57Bl/6 mice (n=338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1-4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1-3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed microCT thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. Results We observed a higher volume of carotid thrombus after dabigatran cessation at 1-3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through arachidonic acid or thrombin, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤3 day) cessation of NOAC therapy, compared with longer-term (≥5 days) cessation, tended to be associated with relatively high stroke severity. Interpretation We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. This article is protected by copyright. All rights reserved.

Unmanned aerial vehicles (UAVs) are often used in mission-critical applications, requiring a critical criterion in flight time. Unfortunately, severe power fluctuations, caused by specific flight patterns, degrade the deliverable capacity of the battery and hamper the flight time. A common approach to mitigating power fluctuations is to employ a hybrid energy storage system using a Li-ion battery with an ultracapacitor (UC). However, the conventional scheme poses inherent problems of low-energy density and power leakage due to the use of the UC and the supplementary hardware required for hybrid storage. In this article, we propose Hydrone, a reconfigurable battery architecture that maximizes the flight time of UAVs, overcoming the previous limitations. Hydrone addresses two key challenges that arise when hybrid energy storage is utilized in UAVs: 1) capacity loss and 2) power leakage. First, the proposed scheme compromises the capacity loss of hybrid storage by using a minimal capacity UC for use as a buffer to counteract the power fluctuations. Second, the power leakage of the hybrid battery is minimized by draining power from the UC only when it is necessary. To this end, the Hydrone architecture provides reconfigurability in hardware and offers two modes of battery operation, i.e., a battery-only mode and a hybrid mode. An appropriate operation is then selected at runtime depending on the flight situation and battery status. To switch modes, we employed a reinforcement learning-based switch control, reflecting the power fluctuation adequately on the flight and battery states. We implemented a hardware prototype to demonstrate the efficiency of Hydrone. Our extensive evaluation shows that the flight time of a UAV is prolonged up to 39% in our experiment setup.

Background Coronavirus disease 2019 (COVID-19) is a growing pandemic that confers augmented risk for right ventricular (RV) dysfunction and dilation; the prognostic utility of adverse RV remodeling in COVID-19 patients is uncertain. Objectives The purpose of this study was to test whether adverse RV remodeling (dysfunction/dilation) predicts COVID-19 prognosis independent of clinical and biomarker risk stratification. Methods Consecutive COVID-19 inpatients undergoing clinical transthoracic echocardiography at 3 New York City hospitals were studied; images were analyzed by a central core laboratory blinded to clinical and biomarker data. Results In total, 510 patients (age 64 ± 14 years, 66% men) were studied; RV dilation and dysfunction were present in 35% and 15%, respectively. RV dysfunction increased stepwise in relation to RV chamber size (p = 0.007). During inpatient follow-up (median 20 days), 77% of patients had a study-related endpoint (death 32%, discharge 45%). RV dysfunction (hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.49 to 4.43; p = 0.001) and dilation (HR: 1.43; 95% CI: 1.05 to 1.96; p = 0.02) each independently conferred mortality risk. Patients without adverse RV remodeling were more likely to survive to hospital discharge (HR: 1.39; 95% CI: 1.01 to 1.90; p = 0.041). RV indices provided additional risk stratification beyond biomarker strata; risk for death was greatest among patients with adverse RV remodeling and positive biomarkers and was lesser among patients with isolated biomarker elevations (p ≤ 0.001). In multivariate analysis, adverse RV remodeling conferred a >2-fold increase in mortality risk, which remained significant (p, Central Illustration

We investigated 10 secondary science teachers’ facilitation of classroom discussions to examine how they went beyond eliciting student ideas to working with student ideas to support sensemaking. We...

The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.), Graphical abstract, The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge…

Background Presentation of life-threatening arrhythmias concomitantly with a new-onset non-ischaemic cardiomyopathy raises concern for an inflammatory cardiomyopathy such as cardiac sarcoidosis or cardiac manifestations of connective tissue disease. Comprehensive workup for specific aetiologies may be unrevealing except for signs of myocardial inflammation identified on cardiac positron emission tomography (PET). Here, we present five cases of such subjects and their clinical course. Case summary We collected clinical, imaging, pathological, and follow-up data of five subjects presenting with arrhythmias and unexplained new-onset cardiomyopathy. Mean age was 56.2 ± 5.8 years. Three subjects presented with ventricular tachycardia and two with atrial arrhythmias. Echocardiography showed a mean left ventricular ejection fraction of 37 ± 9%. Significant coronary artery disease was ruled out in all cases as the cause of the cardiomyopathy. All patients underwent cardiac magnetic resonance imaging (MRI) and PET scan at presentation and follow-up. In all patients, cardiac MRI revealed hyperenhancement in epicardial and mid-myocardial pattern in a non-coronary distribution, while PET scan revealed fluorodeoxyglucose (FDG) mismatch defects in multiple foci in a non-coronary distribution. Right ventricular biopsy was obtained in all patients and revealed interstitial fibrosis and cardiomyocyte hypertrophy. On median follow-up of 210 days, all subjects had improvement in both heart failure symptoms and arrhythmias and repeat PET in four out of five patients showed decreased inflammation. Discussion A high level of suspicion for inflammatory cardiomyopathy is needed in patients presenting with new unexplained cardiomyopathy and arrhythmias. A cardiac FDG-PET should be considered for diagnosis if cardiac inflammation is in the differential. This can inform further decisions regarding targeted immunomodulation therapy that may be helpful in this cohort.

Biopsies with conventional forceps beyond the operating range are difficult and cumbersome. Thus, we developed a new bendable forceps for improved access to gastrointestinal lesions and evaluated its technical feasibility. A bendable forceps was constructed with two channels and a two-stage knob. The bending motion-related structures were designed to improve the range of motion. For the evaluation of the forceps, we used 2 gastrointestinal simulators: an ex vivo porcine model, and an in vivo porcine model with some difficult endoscopic biopsy cases. All evaluations were performed by 5 expert endoscopists and an expert pathologist. Compared with the conventional forceps, the bendable forceps had greater efficacy in the simulator (6.2 ± 0.4 vs. 1.96 ± 0.2, p

The lack of personal and economic attributes in emerging public transit big data (such as smart card data) is a general issue that needs to be addressed. Passengers in the public transit network are from different socioeconomic classes, and their trip attributes usually depend on their personal and economic attributes. For instance, age as a demographic attribute plays an important role in trip attributes; adolescent passengers travel to school, young professionals travel to work, and old passengers travel to medical facilities more often. Relations between the socioeconomic and trip attributes of the passengers can be examined by developing a Bayesian network that represents the relations between the attributes by directed acyclic graphs, and calculating the joint and conditional probability values in the graph. This study infers the socioeconomic attributes of the public transit passengers from the trip attributes through developing a Bayesian network. Considered socioeconomic attributes are age, gender, and income; considered trip attributes are start time and duration of the trip, stay duration, and available origin and destination land use types. First, potential structures of the Bayesian network are examined by comparing network scores and arc strength test. After learning the network’s parameters, the reasoning is done through both prediction and diagnosis in the network. Also, the most likely combinations of the socioeconomic and trip attributes are discovered. The case study for developing the Bayesian network is a Household Travel Survey dataset from Queensland, Australia, that contains both socioeconomic and trip attributes. Results clearly show how the socioeconomic attributes can be inferred from the trip attributes. Discovered probability distributions can be used to enrich the smart card datasets with the socioeconomic attributes. Moreover, the Bayesian classifier is applied to the dataset to validate the capability of the model in predicting the socioeconomic attributes. In the end, the developed network is implemented on a set of smart card records to discuss the potential applications.

Metformin has been widely used as an antidiabetic drug, and reported to inhibit cell proliferation in many cancers including non-small cell lung cancer (NSCLC). In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations. We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. The combination therapy synergistically decreased cell viability in treatment with low doses of two drugs, while it gave antagonistic effect with high doses. These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells.

Purpose To use delayed enhancement cardiac magnetic resonance (DE-CMR) as a reference standard to evaluate the prevalence and predictors of right atrial (RA) thrombus. Methods In this retrospective study, 130 cancer patients with central venous catheters undergoing CMR from August 2012–January 2018 were included. CMR (cine-CMR and DE-CMR) and echocardiography were interpreted for RA thrombus blinded to other imaging results and clinical data. RA thrombus properties including the number of discrete masses, size, total thrombus area, and perimeter were also assessed. Cine-CMR was also used to quantify cardiac structure and function as markers of RA thrombus. Student's t-test was used to assess continuous variables; chi-square or Fisher's exact test were used to assess categorical variables. Results 31/130 (24%) patients had RA thrombus on DE-CMR. Echocardiography (attained in 64% of the study population) demonstrated moderate sensitivity and specificity (75%, 90% respectively) in relation to DE-CMR; cine-CMR performance was higher (sensitivity 90%, specificity 98%). Patients with and without RA thrombus had similar right-sided structure/function and cancer diagnosis. Catheter depth approached significance in patients with RA thrombus (p = 0.05). 13% of patients with RA thrombus had concomitant pulmonary embolism within 60 days of CMR vs. 2% of patients without RA thrombus (p = 0.03). Embolic events were independent of RA thrombus size (p = 0.66). Conclusion Morphologic imaging by cine-CMR and echocardiography provide limited diagnostic utility for RA thrombus as established by DE-CMR tissue characterization. Catheter-associated RA thrombus occurs independently of right-sided structure or function and is associated with clinical embolic events and catheter depth.

Purpose Echocardiography (echo) is widely used for right ventricular (RV) assessment. Current techniques for RV evaluation require additional imaging and manual analysis; machine learning (ML) approaches have the potential to provide efficient, fully automated quantification of RV function. Methods An automated ML model was developed to track the tricuspid annulus on echo using a convolutional neural network approach. The model was trained using 7791 image frames, and automated linear and circumferential indices quantifying annular displacement were generated. Automated indices were compared to an independent reference of cardiac magnetic resonance (CMR) defined RV dysfunction (RVEF

Background and aims Exercise training (ET) helps treat atherosclerosis. However, many patients stop regular ET for various reasons. The effect of detraining on atherosclerosis is not well studied. We examined the effects of ET vs. short-term detraining on atheromatous matrix-metalloproteinase (MMP) activity in preexisting plaque and circulating cytokines/lipids. Methods and results Eighteen-week-old apolipoprotein-E−/− mice (n = 56) on a Western diet underwent: 1) ET for 6-weeks (ET5+1), 2) ET for 5-weeks and detraining for 1-week (ET5+0), 3) ET for the last 1-week (ET0+1), or 4) no treadmill ET at all for 6-weeks (ET0+0). Atheromatous MMP-activity was visualized using molecular imaging with an MMP-2/9-activatable near-infrared-fluorescent probe. Compared with no ET (ET0+0), regular ET (ET5+1) decreased carotid atheromatous MMP activity, but this protective effect was significantly blunted by short-term detraining (ET5+0). Short-term detraining after longer-term ET showed a reduction in MMP-activity similar to short-term ET (ET0+1). Blood levels of lipids and cytokines paralleled the molecular imaging results: exercise caused higher levels of high-density lipoprotein, adiponectin, and interleukin-10 and lower levels of vascular cell adhesion molecule, monocyte chemoattractant protein-1, interleukin-1β, and low-density lipoprotein. However, this beneficial effect was short-lived, with the ET5+0 group being similar to the ET0+0 group, and the ET0+1 group being similar to the ET5+1 group. The effect of exercise can be modeled with an exponential-decay of the protective factor of about 15%/day. Conclusions Even short-term detraining reduces atheroprotective effects, and tips the balance towards atherosclerosis. This suggests that ET, to be effective, needs to be prolonged and regular, and that detraining should be avoided.

IMPORTANCE Detailed incidence data for cataract surgery in the general population are limited, yet important for determining the surgical needs of the community and formulation of healthcare policies. BACKGROUND To report incidence rates of cataract surgery in South Korea. DESIGN Nationwide, retrospective population-based study. PARTICIPANTS This study involved the entire population of South Korea (n = 47 990 761); 2 236 107 eyes of 1 591 176 patients confirmed as having cataract surgery from 1 January 2011 to 31 December 2015 were included. METHODS Data for all patients who underwent primary cataract surgery in South Korea were retrieved using Korean Electronic Data Interchange and Korean Standard Classification of Diseases-7 codes. Annual incidence rates were calculated and adjusted to the national population data for the corresponding year. MAIN OUTCOME MEASURES The average incidence of cataract surgery during the 5-year study period was estimated using population data from the 2010 Korean census. RESULTS The incidence of cataract surgery increased from 8.54/1000 person-years in 2011 to 9.67/1000 person-years in 2015. The probability of second-eye surgery within 12 months after the first-eye surgery increased from 42.98% in 2011 to 48.01% in 2015. In total, 85.72% of surgeries were performed in non-rural areas: 43.18% in individuals with a higher household income and 76.65% in primary healthcare centres. The rate of vitrectomy for posterior capsular rupture was 0.72%. CONCLUSIONS AND RELEVANCE The incidence of cataract surgery in South Korea is increasing over time. Our findings are expected to aid in the formulation of future healthcare policies concerning cataract surgery in South Korea.

The pattern of activities by transit passengers and the factors affecting this pattern are recently addressed in the literature. Also, the pattern of trips and the factors affecting trips are the subject of many studies. However, little is known about the correlation between the activity and trip of passengers in the public transit network. This study investigates how similar are activities of passengers if they have similar trips (or vice versa)? And what factors impact the similarity of the activity and trip of passengers? Answering these questions is useful in understanding the mobilization patterns of passengers and developing group-based transit services. Also, smart card data have provided an opportunity, which was not available before, to analyze the activity and trip of the passengers in a large scale network. In this paper, the correlation between activity similarity and trip similarity of public transit passengers is investigated. The correlation between the activity and trip of the passengers is analyzed using histograms, Pearson correlation coefficient, conditional probabilities, and hexagonal binning technique. In addition, the impact of trip length and duration on the activity and trip similarity are examined using histograms and hexagonal binning diagrams. The proposed methodology is implemented for two-day smart card data in Brisbane, Australia. Results show that it is more likely to have the activity similarity when there is a trip similarity than having the trip similarity when there is activity similarity. Also, there is a nonlinear correlation between the activity and trip similarity with the trip length and duration.

Myeloproliferative neoplasm (MPN) has been associated with pulmonary hypertension (PH) on the basis of small observational studies, but the mechanism and clinical significance of PH in MPN are not well established. The aims of this study were to expand understanding of PH in a well-characterized MPN cohort via study of PH-related symptoms, mortality risk, and cardiac remodeling sequalae of PH using quantitative echocardiographic methods.The population comprised a retrospective cohort of patients with MPN who underwent transthoracic echocardiography: Doppler-derived pulmonary arterial systolic pressure applied established cutoffs for PH (≥35 mm Hg) and advanced PH (≥50 mm Hg); right ventricular (RV) performance was assessed via conventional indices (tricuspid annular plane systolic excursion [TAPSE], S') and global longitudinal strain. Symptoms and mortality were discerned via standardized review.Three hundred one patients were studied; 56% had echocardiography-demonstrated PH (20% advanced) paralleling a high prevalence (67%) among patients with invasively quantified PASP. PH was associated with adverse left ventricular (LV) remodeling indices, including increased myocardial mass and diastolic dysfunction (P ≤ .001 for all): LV mass and filling pressure (P .01) were associated with PH independent of LV ejection fraction. RV dysfunction by strain and TAPSE and S' increased in relation to PH (P ≤ .001) and was about threefold greater among patients with advanced PH compared with those without PH. Patients with RV dysfunction were more likely to report dyspnea, as were those with advanced PH (P .05). During median follow-up of 2.2 years, all-cause mortality was 27%. PH grade (hazard ratio, 1.9; 95% CI, 1.1-3.0; P = .012) and TAPSE- and S'-demonstrated RV dysfunction (hazard ratio, 3.3; 95% CI, 1.3-8.2; P = .01) were independently associated with mortality; substitution of global longitudinal strain for TAPSE and S' yielded similar associations of RV dysfunction with death (hazard ratio, 3.2; 95% CI, 1.5-6.7; P = .003) independent of PH.PH is highly prevalent in patients with MPN and is linked to LV diastolic dysfunction; echocardiography-quantified RV dysfunction augments risk for mortality independent of PH.

Background Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain. Methods The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE. Results Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p 2/m2 [CI 1.19–3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02–1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95–30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p p mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028). Conclusions MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.

Human placental tissues have variable rates of SARS-CoV-2 invasion resulting in consistently low rates of fetal transmission suggesting a unique physiologic blockade against SARS-CoV-2. Angiotensin-converting enzyme (ACE)-2, the main receptor for SARS-CoV-2, is expressed as cell surface and soluble forms regulated by a metalloprotease cleavage enzyme, ADAM17. ACE-2 is expressed in the human placenta, but the regulation of placental ACE-2 expression in relation to timing of maternal SARS-CoV-2 infection in pregnancy is not well understood. In this study, we evaluated ACE-2 expression, ADAM17 activity and serum ACE-2 abundance in a cohort of matched villous placental and maternal serum samples from Control pregnancies (SARS-CoV-2 negative, n=8) and pregnancies affected by symptomatic maternal SARS-CoV-2 infections in the 2nd trimester (“2ndTri COVID”, n=8) and 3rd trimester (“3rdTri COVID”, n=8). In 3rdTri COVID as compared to control and 2ndTri-COVID villous placental tissues ACE-2 mRNA expression was remarkably elevated, however, ACE-2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE-2 was also significantly increased in the maternal serum from 3rdTri COVID infections as compared to control and 2ndTri-COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE-2 protein may be the result of ACE-2 shedding. Overall, this work highlights the importance of ACE-2 for ongoing studies on SARS-CoV-2 responses at the maternal-fetal interface.

BackgroundDeep brain stimulation (DBS) targeting the subthalamic nucleus (STN) often shows variable outcomes on treating gait dysfunction in Parkinson’s disease (PD). Such variability may stem from which specific neuronal pathways are modulated by DBS and the extent to which those pathways are modulated relative to one another.ObjectiveLeveraging ultra-high-field (7T) imaging data and subject-specific computational models, this study investigated how activation of seven distinct pathways in and around STN, including the pallidopeduncular and pedunculopallidal pathways, affect step length at clinically-optimized STN-DBS settings.MethodsPersonalized computational models were developed for 10 subjects with a clinical diagnosis of PD and with bilateral STN-DBS implants.ResultsThe subject-specific pathway activation models showed a significant positive association between activation of the pedunculopallidal pathway and increased step length, and negative association on step length with pallidopeduncular pathway and hyperdirect pathway activation.ConclusionsThe STN region includes multiple pathways, including fibers of passage to and from the mesencephalic locomotor area. Future clinical optimization of STN-DBS should consider these fibers of passage in the context of treating parkinsonian gait.

We report experimental investigation of PD in Yb-doped fibers. From fluorescence spectra while pumping at 1018 nm and 976 nm, we can attribute the PD to existence of oxygen deficiency centers and its strong dependence on the excited Yb3+ ion density. Furthermore, we investigated the impact of PD on the laser amplification experiment, demonstrating that the tandem pumping at 1018 nm could dramatically reduce the PD-induced background loss compared to the LD pumping at 976 nm due to the low excited Yb3+ density. We will discuss the way to mitigate the PD in high power Yb fiber lasers.

Whereas left atrial (LA) strain has been well-validated using transthoracic echocardiography (TTE), its detection using transesophageal echocardiography (TEE) has not been studied. Conventional transesophageal views are known to be limited due to the posterior location of the LA. Here, the feasibility and accuracy of the deep transgastric long-axis LA focused view for peak atrial longitudinal strain (PALS) quantification was tested.This was a retrospective study of patients who underwent elective cardiac surgery between 2018 and 2020. TEE deep transgastric long-axis view was compared to TTE 4-chamber atrial focused view as the reference standard. LA area, volume, and PALS were quantified independently.At Weill Cornell Medicine, a single, large academic medical center.The population comprised 42 patients undergoing cardiac surgery who had a TTE and TEE within 14.9 ± 20.8 days.TTE, TEE, and cardiac surgery.TEE-derived PALS strongly correlated with TTE- derived PALS (r = 0.92, p0.001), though absolute PALS were lower (20.7 ± 6.0% v 25.7 ± 6.8%; p0.001). Mean TEE-derived atrial length was similar to TTE-derived length (5.18 ± 0.61 cm v 5.24 ± 0.61 cm; p = 0.38), but mean LA area was significantly smaller (16.7 ± 3.5 cmThis exploratory study supported the feasibility of TEE for assessing LA longitudinal strain. There was an excellent correlation between atrial strain derived via TEE versus TTE, although values tended to be smaller on TEE, and bias between values was highly variable, suggesting that the values were not interchangeable.

Background: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). Methods: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association’s COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. Results: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03–1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10–1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65–1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84–1.33]). Conclusions: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

Recent evidence indicates that our understanding of the relationship between cardiac function and ischemic stroke remains incomplete. The Cardiovascular Health Study enrolled community-dwelling adults ≥ 65 years old. We included participants with speckle-tracking data from digitized baseline study echocardiograms. Exposures were left atrial reservoir strain (primary), left ventricular longitudinal strain, left ventricular early diastolic strain rate, septal e’ velocity, and lateral e’ velocity. The primary outcome was incident ischemic stroke. Cox proportional hazards models were adjusted for demographics, image quality, and risk factors including left ventricular ejection fraction and incident atrial fibrillation. Among 4,000 participants in our analysis, lower (worse) left atrial reservoir strain was associated with incident ischemic stroke (HR per SD absolute decrease, 1.14; 95% CI 1.04–25). All secondary exposure variables were significantly associated with the outcome. Left atrial reservoir strain was associated with cardioembolic stroke (HR per SD absolute decrease, 1.42; 95% CI 1.21–1.67) and cardioembolic stroke related to incident atrial fibrillation (HR per SD absolute decrease, 1.60; 1.32–1.95). Myocardial dysfunction that can ultimately lead to stroke may be identifiable at an early stage. This highlights opportunities to identify cerebrovascular risk earlier and improve stroke prevention via therapies for early myocardial dysfunction.

Journal of the American Society of Echocardiography - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le mercredi 3 novembre 2021

Nonalcoholic steatohepatitis (NASH) is the most prevalent chronic liver disease worldwide and increases the risk for hepatocellular carcinoma (HCC) in developed countries. However, no medications have been approved to protect against NASH-driven HCC. Dapagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, improves hyperglycemia by promoting glycosuria. We investigated whether dapagliflozin prevents NASH-driven HCC using a mouse model. Diethylnitrosamine (25 mg/kg) was intraperitoneally injected into 2-week-old C57BL6/J male mice, followed by either normal chow diet or 60% high-fat diet (HFD) for 30 weeks with or without dapagliflozin, 0.003% (w/w). HFD-fed mice without dapagliflozin had an increased number of tumor on liver surface compared with chow-fed mice (77.0 vs. 12.5/per mouse; n=6 per group; p=0.01). The number of liver tumors was significantly lower in dapagliflozin treated group (19.5/per mouse in dapagliflozin-treated HFD-fed mice; n=6) than that in HFD-fed mice without dapagliflozin (p=0.03). Dapagliflozin treatment numerically reduced body weight and fasting blood glucose compared with HFD-fed mice without dapagliflozin (41.0 vs. 40.2 g, p=0.94 for body weight, and 196.3 vs. 170.8 mg/dL, p=0.34 for fasting blood glucose). In addition, several human HCC cell lines (Huh 7, HepG2, and Hep3B) expressed SGLT-2 protein. Thus, it is possible that dapagliflozin might directly modulate HCC development via SGLT-2 inhibition. In conclusion, dapagliflozin attenuates NASH-associated HCC development possibly via its direct effect on HCC. Disclosure M. Lee: None. H. Lee: None. E. Kang: None. Y. Kim: None. S. Lee: None. H. Kim: None. S. Lee: None. J. Kim: None. S. Kim: None. R. Kim: None. H. Park: None.